Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

Objective

Current international guidelines recommend home blood pressure (BP) measurement and low sodium and high potassium intakes for the management of hypertension. We hypothesized that increased home BP measurement may result in more effective management of sodium and potassium intakes and BP.

Methods

We examined associations of home BP measurement days with changes in the urinary sodium-to-potassium (Na/K) ratio, estimated salt and potassium intakes and BP. We included 209 healthy participants (mean age, 55.9 years; 56.5% women) from a prospective cohort study. We examined 1-year data on self-measured home BP and spot urine samples.

Results

Median (interquartile range) days of home BP measurement was 324 (225–358) over 1-year. Baseline mean (SD) Na/K ratio, salt and potassium intakes, morning and evening SBP, and morning and evening DBP were 3.8 (2.3), 8.5 (1.9) g/day, 1833.5 (416.5) mg/day, 120.4 (14.0) mmHg, 118.2 (14.2) mmHg, 79.2 (10.1) mmHg, and 76.2 (10.1) mmHg, respectively. In multivariable-adjusted linear regression , β (standard error) per 10 days increase in number of home BP measurement were −0.031 (0.017) for Na/K ratio, −0.036 (0.015) for salt intake, −1.357 (2.797) for potassium intake, −0.178 (0.064) for morning SBP, −0.079 (0.041) for morning DBP, −0.109 (0.067) for evening SBP and −0.099 (0.045) for evening DBP. Additionally, relationships persisted for men and women, but changes in salt intake were more pronounced among participants taking antihypertensive medication (interaction P = 0.002).

Conclusion

Continuous measurement of home BP may lead not only to self-monitoring of BP, but also to declines in salt intakes and some BP indices.

DOI： 10.1097/MBP.0000000000000705

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Based on data from national surveys, the prevalence of hypertension rests at 40-60% in Japan, the USA, and in European countries. This suggests there has been little progress in the prevention of hypertension in even high-income countries despite their well-functioning health systems. In particular, compared with the USA and European countries, the improvement in awareness, treatment, and control of hypertension has been relatively low in Japan. For example, the rates of hypertension awareness, treatment, and control were observed, respectively, in 60-70%, 50-60%, and 20-30% of Japanese compared with 80-90%, 70-80%, and 50-60% of US citizens in the years around 2015. The lower proportions in Japan might be explained by the slower progress in lowering the accepted thresholds for diagnosis of hypertension and initiation of treatment compared with Western countries; however, the underlying reasons for the differences warrant further study. The high prevalence (>40%) of uncontrolled hypertension in even high-income countries has major implications for the prevention of cardiovascular disease. Health policy and research on early control of high blood pressure at the individual and public health levels will contribute to decreases in the prevalence of hypertension. Furthermore, proactive treatment and strict adherence to intensified antihypertensive treatment guidelines will more effectively achieve targeted blood pressure levels. In this context, it is important to continue to carefully monitor and compare trends in hypertension across countries.

DOI： 10.1038/s41371-021-00534-3

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Onco-hypertension has been proposed, although associations of high blood pressure (BP) with cancer risk remain inconsistent. We examined associations of high BP with risk of mortality from stomach, lung, colorectal, liver, and pancreatic cancers independent of possible confounders in an analysis that excluded deaths within the first 5 years of follow-up to consider the reverse causality. In a prospective cohort representative of the general Japanese population (1980-2009), we studied 8088 participants (mean age, 48.2 years; 56.0% women) without clinical cardiovascular disease or antihypertensive medication at baseline. Fine-Gray competing risks regression was used to estimate hazard ratios for 10 mmHg higher BP adjusted for confounders including smoking, alcohol-drinking, obesity, and diabetes mellitus. During 29-year follow-up, 159 (2.0%), 159 (2.0%), 89 (1.1%), 86 (1.1%), and 68 (0.8%) participants died from stomach, lung, colorectal, liver, and pancreatic cancers, respectively. We observed a positive association of high BP with risk of colorectal cancer mortality but not with mortality risks from any other cancers. The association with colorectal cancer mortality for systolic and diastolic BP was evident in those aged 30-49 years (hazard ratios 1.43 [95% confidence interval, 1.22-1.67] and 1.86 [1.32-2.62], respectively) but not in those aged 50-59 years and ≥60 years (P for age interaction <0.01 for systolic and diastolic BP). The associations with colorectal cancer mortality were similar in the analyses stratified by smoking, alcohol-drinking, obesity, and diabetic status. In conclusion, high BP among young to middle-aged adults was independently associated with risk of colorectal cancer mortality later in life.

DOI： 10.1038/s41440-023-01497-3

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AIMS: It remains inconclusive regarding alcohol intake and stroke risk because determining risk factors depends on the specific pathogenesis of stroke. We used the variant rs671 in the aldehyde dehydrogenase 2 gene (ALDH2) as an instrument to investigate the causal role of alcohol intake in cerebral small- and large-vessel diseases. METHODS: We studied 682 men (mean age, 70.0 years), without stroke, in a cross-sectional Mendelian randomization analysis. We assessed small-vessel diseases (SVDs), which comprised lacunar infarcts, white matter hyperintensities (WMHs), and cerebral microbleeds, and large intracranial artery stenosis (ICAS) on brain magnetic resonance imaging. RESULTS: The median (25%tiles, 75%tiles) alcohol consumption by ALDH2-rs671 inactive A allele (n=313 [45.9%]) and non-A allele (n=369 [54.1%]) carriers was 3.5 (0.0, 16.0) and 32.0 (12.9, 50.0) g/day, respectively. Non-A allele carriers had higher prevalent hypertension and lower low-density lipoprotein cholesterol concentrations than A allele carriers. In age-adjusted ordinal logistic regression for graded burden, odds ratios (95% confidence intervals) for total SVDs, lacunar infarcts, WMHs, cerebral microbleeds, and ICAS in non-Aallele carriers were 1.46 (1.09-1.94), 1.41 (0.95-2.08), 1.39 (1.05-1.85), 1.69 (1.06-2.69), and 0.70 (0.50-0.98), respectively, compared with A allele carriers. These associations attenuated to statistical non-significance after considering covariates and amount of alcohol intake. CONCLUSIONS: Our findings suggest a positive association of alcohol consumption with risk of cerebral SVDs and its inverse association with risk of large-vessel disease through intermediaries, such as hypertension or low-density lipoprotein cholesterol. These findings provide insight into potential causal mechanisms linking alcohol consumption with stroke risk.

DOI： 10.5551/jat.64222

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AIM: Few studies have compared the strength in the associations of anthropometric and computed tomography (CT)-based obesity indices with coronary artery calcification (CAC), aortic artery calcification (AoAC), and aortic valve calcification (AVC). METHODS: We assessed cross-sectcional associations of anthropometric and CT-based obesity indices with CAC, AoAC, and AVC. Anthropometric measures included body mass index (BMI), waist circumference, hip ircumference, waist-to-hip circumference ratio, and waist-to-height ratio in 931 men (mean age, 63.7 years) from a population-based cohort. CT images at the L4/5 level were obtained to calculate the areas of abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), total adipose tissue (TAT), VAT-to-SAT ratio (VSR), and VAT-to-TAT ratio (VTR). CAC, AoAC, and AVC were quantified using the Agatston score based on CT scanning. RESULTS: CAC, AVC, and AoAC were present in 348 (62.6%), 173 (18.6%), and 769 (82.6%) participants, respectively. In multivariable models adjusting for age, lifestyle factors, and CT types (electron beam CT and multidetector row CT), anthropometric and CT-based obesity indices were positively associated with CAC (p＜0.01). Conversely, VAT-to-SAT ratio and VAT-to-TAT ratio were positively associated with AoAC (p＜0.01). Any obesity indices were not associated with AVC. CONCLUSIONS: The strength of the associations of obesity indices with subclinical atherosclerosis varied according to the anatomically distinct atherosclerotic lesions, among men.

DOI： 10.5551/jat.64096

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Ambient temperature and blood pressure (BP) are closely related; however, few studies have examined the association of out-of-office BP with indoor or outdoor temperature. The effect of the difference between indoor and outdoor temperatures on BP also remains unknown. Therefore, this study aimed to investigate the association of indoor and outdoor temperatures and their difference with home BP. We studied healthy 352 participants (mean age, 49.8 years; 46.0% women) from a population-based cohort using 2-year data on temperature and self-measured home BP. We measured home BP and indoor temperature at the same time in the morning and evening every day. Outdoor temperature during the same period was based on national data. We observed 82,900 home BP measurements in the morning and 66,420 in the evening. In the mixed-effects model adjusted for age, sex, and possible confounders, indoor temperature was inversely associated with systolic and diastolic BP in the morning and evening. A 1 °C increase in indoor temperature reduced systolic and diastolic BP by 0.37 and 0.22 mmHg, respectively, in the morning and by 0.45 and 0.30 mmHg, respectively, in the evening (all P-values<0.001). The magnitude of associations was stronger for indoor than outdoor temperature. Similarly, a 1 °C increase in indoor temperature above outdoor temperature decreased systolic and diastolic BP by 0.33 and 0.12 mmHg, respectively, in the morning and by 0.45 and 0.26 mmHg, respectively, in the evening independent of outdoor temperature (all P-values <0.001). In conclusion, controlling indoor temperature is important to stabilize home BP levels.

DOI： 10.1038/s41440-022-01059-z

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

Abstract

Aims

The potential effect of alcohol consumption on coronary heart disease (CHD) remains unclear. We used the variant rs671 in the aldehyde dehydrogenase 2 gene (ALDH2) as an instrument to investigate the causal role of alcohol intake in subclinical and clinical CHD.

Methods

We conducted two Mendelian randomization studies: a cross-sectional study of coronary artery calcification (CAC) on computed tomography of 1029 healthy men (mean age, 63.8 years) and a case-control study of 421 men with CHD (acute coronary syndrome [ACS] or stable angina pectoris) who underwent coronary revascularization and 842 age-matched male controls.

Results

In the CAC study, medians (25%tiles, 75%tiles) of alcohol consumption by ALDH2-rs671 *2 homozygotes (n = 86 [8.4%]), *1*2 heterozygotes (n = 397 [38.5%]), and *1 homozygotes (n = 546 [53.1%]) were 0.0 (0.0, 0.0), 28.0 (0.0, 129.0), and 224.0 (84.0, 350.0) g/week, respectively. In age-adjusted Poisson regression with robust error variance, compared with *2 homozygotes, relative risks for prevalent CAC score &amp;gt;0, ≥100, and ≥300 in *1 homozygotes were 1.29 (95% confidence interval, 1.06-1.57), 1.76 (1.05-2.96), and 1.81 (0.80-4.09), respectively. In age-adjusted ordinal logistic regression for CAC distributions, we observed higher odds among *1 homozygotes (odds ratio, 2.19 [1.39-3.46]) and even among *1*2 heterozygotes (1.77 [1.11-2.82]) compared with *2 homozygotes. In the case-control study, conditional logistic regression revealed lower prevalence of *1 homozygotes among men with CHD (odds ratio, 0.54 [0.35-0.82]), especially ACS (0.46 [0.27-0.77]), than controls.

Conclusion

Our findings indicate a positive association of alcohol consumption with CAC burden but an inverse association with clinical CHD, especially ACS.

DOI： 10.1093/eurjpc/zwac156

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OBJECTIVE: We aimed to investigate the effect of ambulatory blood pressure (BP) on aortic valve calcification (AVC) and coronary artery calcification (CAC), which are subclinical atherosclerotic diseases. METHODS: In this population-based, cross-sectional study, we assessed office BP, mean ambulatory BP (24-h, awake, and asleep), and variability of ambulatory BP, as determined by the coefficient of variation (awake and asleep). AVC and CAC were quantified using an Agatston score (>0) based on computed tomography scanning. We calculated relative risks (RRs) and 95% confidence intervals (CIs) with a 1-standard deviation increment in each BP index for the presence of AVC and CAC using a multivariate-adjusted Poisson regression with robust error variance. RESULTS: Of 483 participants (mean age: 66.8 years), 154 (31.9%) and 310 (64.2%) had AVC and CAC, respectively. The presence of AVC was associated with office systolic BP (SBP; RR, 1.15; 95% CI, 1.03-1.28), awake diastolic BP (DBP) variability (RR, 1.12; 95% CI, 1.01-1.25), and asleep SBP variability (RR, 1.14; 95% CI, 1.03-1.27). The presence of CAC was associated with office SBP (RR, 1.08; 95% CI, 1.01-1.15), mean 24-h SBP (RR, 1.10; 95% CI, 1.04-1.16), mean awake SBP (RR, 1.11; 95% CI, 1.04-1.17), mean asleep SBP (RR, 1.07; 95% CI, 1.01-1.13), and asleep SBP variability (RR, 1.07; 95% CI, 1.01-1.13). CONCLUSION: These findings highlight the association of ambulatory BP indices with both AVC and CAC, but with different effects on their presences.

DOI： 10.1097/HJH.0000000000003147

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Increased ventricular premature complexes (VPCs) are associated with a higher risk of cardiac morbidities. However, little information is available on the risk factors of Western general populations. Therefore, we aimed to assess the frequency and associated factors of VPCs in healthy general Japanese men. We conducted a population-based cross-sectional study in 517 men, aged 40 to 79 years, using 24-hour Holter electrocardiography. Age, body mass index, height, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol, resting heart rate, diabetes mellitus, hypertension, physical activity, smoking, alcohol consumption, lipid-lowering therapy were included in multivariable negative binomial regression to assess independent correlates for the number of VPCs per hour. We observed at least 1 VPC in 1 hour in 429 men (83%). In multivariable negative binomial regression adjusted for all covariates simultaneously, age (risk ratio [95% confidence interval] 1.91 [1.56 to 2.33] per 1-SD increment), height (1.17 [1.04 to 1.49] per 1-SD increment), resting heart rate(1.34 [1.02 to 1.77] per 1-SD increment), diabetes mellitus (2.36 [1.17 to 4.76] ), hypertension (1.90 [1.03 to 3.50]), physical activity (0.67 [0.47 to 0.97] ), current smoking (4.23 [1.86 to 9.60] ), past smoking (2.08 [1.03 to 4.19] ), current light alcohol consumption (0.16 [0.04 to 0.64] ), and lipid-lowering therapy (0.47 [0.23 to 0.96] ) were independently associated with VPCs frequency. In conclusion, VPCs frequency was independently associated with age, height, resting heart rate, diabetes mellitus, hypertension, physical activity, smoking, alcohol consumption, and lipid-lowering therapy.

DOI： 10.1016/j.amjcard.2021.12.046

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：(公社)日本産業衛生学会  

OBJECTIVES: Problematic internet use (PIU) has been suggested in relation to psychological symptoms among schoolteachers, but the relationship with physical symptoms remains unclear. We examined whether PIU or longer Internet usage time is associated with neck pain in schoolteachers. METHODS: We conducted a cross-sectional study among 2582 teachers aged 20 years or older (35.6% women) in Shimane and Tottori, Japan in 2018. Neck pain was defined as ≥5 points on the Neck Disability Index. The Compulsive Internet Use Scale (CIUS) was used to assess PIU. Internet usage time on weekdays and weekends was divided into five groups: 0, 1-29, 30-59, 60-119, and ≥120 min/day. Logistic regression analysis was conducted to examine the association of the CIUS score and Internet usage time on weekdays or weekends with neck pain, adjusting for sex, age, position at school, insomnia, and psychological distress. RESULTS: We observed 800 (31.0%) teachers with neck pain. The median (interquartile range) of their CIUS scores was 7 (2, 14). A higher CIUS score was independently associated with a higher prevalence of neck pain (odds ratio of 4th vs. 1st quartiles, 1.41; 95% confidence interval, 1.06-1.87; trend P = .006). Compared with non-Internet users, Internet users on weekdays had almost double the odds of neck pain although the difference did not reach the customary level for designating statistical significance. CONCLUSIONS: In conclusion, teachers with higher scores in CIUS were associated with a higher prevalence of neck pain in Japan, suggesting adults with PIU being at risk of physical disorders.

DOI： 10.1002/1348-9585.12298

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: Data are sparse regarding the impact of sodium and potassium intakes on serial blood pressure (BP) levels during long-term follow-up. METHODS: Among 1007 Coronary Artery Risk Development in Young Adults participants (mean age, 30.2 years; 53% blacks; 57% women) who had at least two 24-h urine samples collected at year 5 (Y5) examination, we assessed associations of urinary sodium and potassium excretions with BP trends and incident hypertension in the subsequent 25 years. Participants were classified by sex-specific medians for averaged 24-h urinary excretions: lower sodium and higher potassium (Na-Lo-K-Hi); higher sodium and lower potassium (Na-Hi-K-Lo); and others. RESULTS: In the adjusted generalized estimating equation model, SBP and DBP greatly increased in the Na-Hi-K-Lo group (n = 185) compared with the Na-Lo-K-Hi group (n = 185), with statistically significant BP differences at Y20, Y25, and Y30 (mean SBP, 3.93, 4.94, and 4.88 mmHg, respectively; and mean DBP, 4.70, 4.95, and 4.59 mmHg, respectively). During 25-year follow-up, among 926 participants without prevalent hypertension by Y5, 381 (41.1%) developed hypertension. In the adjusted Cox proportional hazards model, the Na-Hi-K-Lo group had hazard ratio (95% confidence interval), 1.45 (1.00-2.10) for incident hypertension compared with the Na-Lo-K-Hi group. The association with incident hypertension was predominant in blacks and white women (race--sex interaction, P = 0.03). Sodium-to-potassium ratio and sodium excretion were positively, whereas potassium excretion was inversely, associated with incident hypertension (all P trend <0.05). CONCLUSION: Our findings highlight the importance of dietary sodium reduction and higher potassium intake for hypertension prevention among young adults.

DOI： 10.1097/HJH.0000000000002802

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

OBJECTIVE: Hypertension and intracranial artery stenosis (ICAS) are closely related; however, few studies have compared the strength of the relationship between strictly measured office and out-of-office blood pressure (BP) measurements. The relationship of day-by-day or short-term variability in BP to asymptomatic ICAS also remains unclear. METHODS: In apparently healthy 677 men (mean age, 70 years) from a population-based cohort, we examined the association of strictly measured office BP and 7-day home BP with ICAS on magnetic resonance angiography. We conducted 24-h ambulatory BP monitoring in 468 of the men. Variability indices included day-by-day, daytime, and night-time variability, nocturnal decline, and morning pressor surge. Any ICAS was defined as either mild (1-49%) or severe (≥50%) stenosis. RESULTS: We observed mild and severe ICAS in 153 (22.6%) and 36 (5.3%) participants, respectively. In multivariable-adjusted Poisson regression with robust error variance, higher SBP in office, home, or ambulatory BP monitoring was associated with the presence of any or severe ICAS. The associations with ICAS were comparable between office, home, and ambulatory SBP (all heterogeneity P values >0.1). Independent of mean SBP, greater nocturnal decline or morning pressor surge, but not day-by-day, daytime, or night-time variability, in SBP was associated with higher burden of any or severe ICAS. CONCLUSION: The magnitude of association of strictly measured office BP for asymptomatic ICAS was comparable with that of BP measured at home or in ambulatory BP monitoring. Circadian BP variation based on ambulatory BP monitoring was positively associated with asymptomatic ICAS burden.

DOI： 10.1097/HJH.0000000000002900

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Ne-Zake is the drinking of alcohol before sleeping for helping to fall asleep and sleep well, and Mukae-Zake is the drinking of alcohol in the morning for "calming down" or "curing hangovers". OBJECTIVE: We sought to examine the relationship of insomnia with Ne-Zake and Mukae-Zake among healthy middle-aged Japanese farmers. METHODS: In a cross-sectional study of 746 participants (mean age, 59.5 years; women, 25.9%), Ne-Zake and Mukae-Zake were defined based on a self-administered questionnaire. Insomnia was defined as the Athens Insomnia Scale Japanese version ≥6 or usage of sleeping pills in the previous year. Logistic regression was used to calculate odds ratio (OR) of insomnia related to Ne-Zake and Mukae-Zake adjusting for sex, age, presence of sleep-related disorders, frequency of alcohol consumption, and quantity of alcohol consumed per one occasion. RESULTS: We observed insomnia, Ne-Zake, and Mukae-Zake in 174 (23.3%), 140 (18.8%), and 37 (5.0%) participants, respectively. After adjustment for demographic and confounding factors, participants with Ne-Zake had a significantly higher prevalence of insomnia (OR 2.00 [95% confidence interval, 1.27-3.16]), compared to those without Ne-Zake. Mukae-Zake was also independently associated with a higher prevalence of insomnia among men (OR 3.26 [1.55-6.87]). Participants with both Ne-Zake and Mukae-Zake had a highly significant association with insomnia (OR 4.77 [2.01-11.3]) than those with neither Ne-Zake nor Mukae-Zake. Additionally, for insomnia, the association of Mukae-Zake was more pronounced than that of Ne-Zake (OR 4.09, 95% CI 1.14-14.7, p = 0.031; and OR 1.81, 95% CI 1.08-3.06, p = 0.026, respectively). CONCLUSION: Ne-Zake and Mukae-Zake were associated with insomnia independent of the quantity and frequency of alcohol consumption among Japanese farmers. This finding can be used for stratifying individuals with insomnia not only to improve sleep hygiene but also to prevent alcohol dependence by informing the general population that alcohol has a negative effect on sleep, contrary to popular beliefs.

DOI： 10.1016/j.alcohol.2020.11.005

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Authorship：Lead author,　Corresponding author   Language：English   Publisher：Japan Epidemiological Association  

DOI： 10.2188/jea.JE20200598

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Authorship：Lead author,　Corresponding author   Language：English   Publisher：Springer Science and Business Media LLC  

DOI： 10.1038/s41440-020-0508-z

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Other Link： http://www.nature.com/articles/s41440-020-0508-z

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

OBJECTIVE: The prognostic implication of isolated systolic hypertension (ISH), defined as SBP at least 140 mmHg and DBP less than 90 mmHg, among young-to-middle-aged adults remains controversial. We examined the association of ISH with cardiovascular disease (CVD) risk in adults aged 30-49 years. METHODS: In a prospective cohort of representative Japanese general populations from the NIPPON DATA80 (1980-2009), we studied 4776 participants (mean age, 39.4 years; 55.4% women) without clinical CVD or antihypertensive medication. Participants were classified as follows: normal blood pressure (BP) (SBP/DBP, <120/<80 mmHg), high-normal BP (120-129/<80 mmHg), elevated BP (130-139/80-89 mmHg), ISH, isolated diastolic hypertension (IDH) (<140/≥90 mmHg), and systolic--diastolic hypertension (SDH) (≥140/≥90 mmHg). RESULTS: ISH was observed in 389 (8.1%) participants. During the 29-year follow-up, 115 participants died of CVD, 28 of coronary heart disease, and 49 of stroke. Cox proportional hazards models adjusted for demographics and CVD risk factors showed that participants with ISH had higher risk of CVD mortality than those with normal BP [hazard ratio (confidence interval), 4.10 (1.87-9.03)]. The magnitude of CVD mortality risk related to ISH was comparable with that related to IDH [3.38 (1.31-8.72)] and not as great as that related to SDH [5.41 (2.63-11.14)]. We found significant associations of ISH with coronary and stroke mortality. The association of ISH with CVD mortality was consistent across men and women and those aged 30-39 and 40-49 years. CONCLUSION: ISH among young-to-middle-aged Japanese adults was independently associated with higher risk of CVD mortality later in life.

DOI： 10.1097/HJH.0000000000002533

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Background and Purpose- Few community-based studies have reported the prevalence of intracranial artery stenosis (ICAS) assessed with magnetic resonance angiography. The aim was to determine the prevalence of ICAS using magnetic resonance angiography in a general population of Japanese men and to investigate the associations between ICAS and conventional cardiovascular risk factors. Methods- The Shiga Epidemiological Study of Subclinical Atherosclerosis randomly recruited and examined participants from Kusatsu City, Shiga, Japan, in 2006 to 2008 (baseline); 740 men returned for follow-up and underwent 1.5 T brain magnetic resonance angiography in 2012 to 2015. Participants were categorized as having no-ICAS, mild-ICAS (1 to <50%), or severe-ICAS (≥50%) in any of the arteries examined. After excluding the men with a history of stroke, 709 men were analyzed using multivariable logistic regression to assess independent associations of conventional cardiovascular risk factors with reference to the no-ICAS group. Results- The participants' mean age was 68.0 years. The age-standardized prevalences of mild and severe-ICAS were 20.7% and 4.5%, respectively (with the population of the 2010 Japanese vital statistics as the reference). Age, hypertension, diabetes mellitus, and dyslipidemia were associated with a higher prevalence of severe-ICAS after simultaneous adjustment for conventional cardiovascular risk factors. Conclusions- In a community-based sample of Japanese men, ICAS was estimated to be present in 25.2%, and related to metabolic risk factors, in addition to hypertension and age. These results support the importance of comprehensive management of conventional cardiovascular risk factors for stroke prevention.

DOI： 10.1161/STROKEAHA.119.025964

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本循環器学会  

BACKGROUND AND PURPOSE: The association between an increased supraventricular ectopic beat (SVEB) and subclinical cerebrovascular disease remains unclear. Given the emerging concept that an increased SVEB is a marker of atrial cardiomyopathy or atherosclerosis burden, we sought to determine whether excessive supraventricular ectopic activity (ESVEA) is associated with a higher burden of subclinical cerebrovascular disease in the middle-aged to older cohort with neither apparent stroke nor atrial fibrillation. METHODS: We conducted a cross-sectional population-based study of 462 men (mean age, 68.1 years) who underwent 24-h Holter electrocardiography and brain magnetic resonance imaging. ESVEA was defined as the presence of >10 SVEBs/h. Subclinical cerebrovascular diseases were defined as silent brain infarct (SBI), white matter hyperintensity (WMH) and intracranial atherosclerotic stenosis (ICAS). The association of ESVEA with the presence of subclinical cerebrovascular diseases was adjusted for potential confounding covariates. RESULTS: A total of 88 (19.0%) participants had ESVEA and 81 (17.5%), 91 (19.7%) and 109 (23.6%) had SBI, WMH and ICAS, respectively. In multivariable-adjusted Poisson regression with robust error variance, ESVEA was associated with the presence of WMH (relative risk, 1.58; 95% confidence interval, 1.06-2.36) and ICAS (relative risk, 1.49; 95% confidence interval, 1.02-2.18), but not with that of SBI (relative risk, 1.32; 95% confidence interval, 0.86-2.01). These associations were consistent when the graded distributions of subclinical cerebrovascular diseases were applied as outcomes in ordinal logistic regression. CONCLUSIONS: The ESVEA was independently associated with higher burdens of WMH and ICAS. This suggests that increased SVEBs might improve risk stratification of individuals at high risk of subclinical cerebrovascular disease and consequently apparent ischaemic stroke.

DOI： 10.1111/ene.13970

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

Background The risk of coronary heart disease remains low in Japan, although distributions of several coronary risk factors have become comparable with those in the United States. We prospectively compared coronary atherosclerosis burden, measured with coronary artery calcium (CAC) progression, between men in the 2 countries. Methods In 2 population-based samples of 1712 US White, Black, Hispanic, Chinese men (baseline, 2000-2002) and 697 Japanese men in Japan (2006-2008) aged 45-74 years without clinical cardiovascular disease, we quantified CAC progression by serial computed tomography with medians of 3.4 and 5.2 years between scans, respectively. Results Among White, Black, Hispanic, Chinese, and Japanese men free of baseline CAC, CAC incidence was observed in 35.2%, 26.9%, 29.2%, 18.9%, and 29.2%, respectively. After adjustment for times between scans, demographics, behaviors, coronary risk factors, and their changes between scans, White men had significantly higher CAC incidence than Japanese men (relative risk, 1.68; 95% CI, 1.13-2.50). Among those with detectable baseline CAC, after similar adjustments, all the US race/ethnic groups had significantly greater annual changes in CAC score (mean [95% CI]: 39.4 [35.2-43.6] for White, 26.9 [21.4-32.4] for Black, 30.6 [24.7-36.5] for Hispanic, and 30.2 [22.6-37.8] for Chinese men) than Japanese men (15.9 [10.1-21.8]). Conclusions We found a higher CAC incidence among US White men and greater increases in existing CAC among all the US race/ethnic groups than among Japanese men in Japan. These differences persisted despite adjustment for differences in coronary risk factors.

DOI： 10.1161/circimaging.118.008104

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Authorship：Lead author,　Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Korean Society of Cardiology  

DOI： 10.4070/kcj.2019.0197

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Other Link： https://synapse.koreamed.org/DOIx.php?id=10.4070/kcj.2019.0197

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

OBJECTIVE: The mechanism by which higher blood pressure (BP) variability causes cardiovascular events remains unclear. Experimental results indicate that alterations in vessel wall tension related to BP variability may initiate atherosclerosis through oscillatory shear stress. We examined associations of home BP variability with subclinical atherosclerosis at four anatomically distinct vascular beds. METHODS: In a cross-sectional population-based study of 1033 Japanese (mean age, 64.0 years; men, 88.7%) without known cardiovascular disease, we defined SBP and DBP variability as variability independent of the mean (VIM) across self-measured home BP values during seven consecutive days and quantified coronary and aortic artery calcification (CAC and AAC) by computed tomography, carotid intima-media thickness (CIMT) by ultrasonography, and ankle-brachial index (ABI). RESULTS: In multivariable adjusted models including mean SBP, higher VIM of SBP was associated with CIMT greater than1.0 mm [relative risk (95% confidence interval) fourth versus first quartile, 1.71 (1.15-2.54)], AAC score greater than 0 [1.08 (1.02-1.15)], and ABI less than 1.1 [1.49 (1.12-1.97)], and linear trends were also statistically significant. However, there was no significant association between VIM of SBP and CAC score greater than 0. Meanwhile, higher VIM of DBP was associated only with AAC score greater than 0. The associations were similar when modeling subclinical atherosclerosis severity as continuous outcomes and were consistent across subgroups based on demographics, behavioural, and cardiovascular risk factors. CONCLUSION: Higher variability in home BP, particularly in home SBP, was associated with greater carotid, aortic, and peripheral but not coronary atherosclerosis burdens independent of the mean home BP.

DOI： 10.1097/hjh.0000000000001810

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ireland Ltd  

Background: The mechanisms by which exercise reduces the risk of coronary heart disease remain poorly understood. Irisin, an exercise-induced polypeptide secreted from skeletal muscles, is proposed to potentially mediate beneficial effects of exercise, especially in metabolic regulation and development of atherosclerosis. We examined whether higher serum irisin levels are associated with lower prevalence and progression of coronary atherosclerosis. Methods and results: We performed a prospective, population-based study of Japanese men aged 40–79 years without known coronary heart disease. We measured baseline serum irisin levels using an enzyme-linked immunosorbent assay and quantified coronary artery calcification (CAC) from serial computed tomography scans. Of 1038 participants (mean age, 63.9 years) at baseline, 670 (64.6%) had prevalent CAC. Of 810 participants at follow-up (median, 5.1 years), 407 (50.3%) experienced CAC progression. In Poisson regression with robust error variance adjusted for age and behavioral factors, serum irisin levels were inversely associated with CAC prevalence (relative risk [RR] of 4th versus 1st quartiles [95% confidence interval], 0.88 [0.78–0.99]
trend P = 0.016) and CAC progression (RR, 0.76 [0.63–0.91]
trend P = 0.002). After further adjustment for cardiometabolic risk factors, the inverse association with CAC prevalence disappeared (RR, 0.95 [0.84–1.08]
trend P = 0.319), but that with CAC progression persisted (RR, 0.77 [0.64–0.93]
trend P = 0.003). These associations were consistent when we applied ordinal logistic regression and across subgroups by cardiometabolic risk factor status. Conclusions: Higher serum irisin levels were associated with less burden of coronary atherosclerosis. This association would be mediated through and beyond traditional cardiometabolic pathways.

DOI： 10.1016/j.ijcard.2018.05.075

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ireland Ltd  

Background and aims: Calcific aortic valve disease (CAVD) is the most common valve disease. Although micronutrients are known to contribute to cardiovascular disease, the relationship with CAVD remains poorly evaluated. We examined the association of serum levels of magnesium, phosphorus, and calcium with prevalence, incidence, and progression of aortic valve calcification (AVC). Methods: We conducted a prospective study in a population-based sample of Japanese men aged 40–79 years without known cardiovascular disease and chronic kidney disease at baseline, and quantified AVC from serial computed tomographic images with the Agatston method. Results: Of 938 participants at baseline (mean age, 63.7 ± 9.9 years), AVC prevalence was observed in 173 (18.4%). Of 596 participants without baseline AVC at follow-up (median duration, 5.1 years), AVC incidence was observed in 138 (23.2%). After adjustment for demographics, behaviors and cardiovascular risk factors, relative risks (95% confidence intervals) in the highest versus lowest categories of serum magnesium, phosphorus, and calcium were 0.62 (0.44–0.86), 1.45 (1.02–2.04), and 1.43 (0.95–2.15), respectively, for AVC prevalence and 0.62 (0.42–0.92), 1.93 (1.28–2.91), and 1.09 (0.77–1.55), respectively, for AVC incidence. Their linear trends of serum magnesium and phosphorus were also all statistically significant. Of 131 participants with baseline AVC, there was no association of any serum micronutrients with AVC progression. Conclusions: Serum magnesium was inversely associated, while serum phosphorus was positively associated with AVC prevalence and incidence, suggesting that these serum micronutrients may be potential candidates for risk prediction or prevention of CAVD, and warranting further studies.

DOI： 10.1016/j.atherosclerosis.2018.03.035

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Arterial stiffness is established as an independent predictor of cardiovascular morbidity and mortality. The objective was to prospectively evaluate association of aortic calcification burden with progression of arterial stiffness in population-based samples of healthy middle-aged men from ERA JUMP cohort (Electron-Beam Computed Tomography and Risk Factor Assessment in Japanese and US Men in the Post-World War II Birth Cohort). Men (n=635) aged 40 to 49 years (207 white American, 45 black American, 142 Japanese American, and 241 Japanese in Japan) were examined at baseline and 4 to 7 years later. Aortic calcification was evaluated from level of aortic arch to iliac bifurcation. Arterial stiffness progression was measured as annual change in brachial-ankle pulse wave velocity. Multivariable-adjusted general linear models were applied to investigate associations of longitudinal change in aortic calcification with arterial stiffness progression in participants overall, as well as in subgroups without or with prevalent aortic calcification at baseline. Annual change in aortic calcification was positively and significantly associated with arterial stiffness progression. In participants with annual changes in aortic calcium score of 0, 1 to 10, 11 to 100, and &gt;100, the adjusted means (SD) for the annual change in brachial-ankle pulse wave velocity were 3.8 (2.2), 7.2 (2.2), 12.2 (1.8), and 15.6 (2.6) cm/s, respectively (P for trend &lt;0.01) adjusted for baseline aortic calcification, arterial stiffness, and standard cardiovascular risk factors. Arterial stiffness was associated with the incidence of aortic calcification over the follow-up period among participants without aortic calcification (n=297) and with an increase in aortic calcification among participants with prevalent aortic calcification at baseline (n=388). Our findings suggest aortic calcification may be causally linked to arterial stiffness.

DOI： 10.1161/HYPERTENSIONAHA.116.08459

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Authorship：Lead author,　Corresponding author   Language：Japanese  

J-GLOBAL

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2017&ichushi_jid=J03571&link_issn=&doc_id=20170329310003&doc_link_id=%2Fcs3cardi%2F2017%2F005201%2F003%2F0020-0028%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcs3cardi%2F2017%2F005201%2F003%2F0020-0028%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1161/jaha.116.003738

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CiNii Article

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

OBJECTIVE: The association between insulin resistance (IR) and coronary artery calcification (CAC) has been uncertain after adjustment for metabolic syndrome components. We aimed to evaluate whether IR is associated with CAC prevalence or progression independently of metabolic syndrome components. APPROACH AND RESULTS: We conducted a population-based study in a random sample of Japanese men aged 40 to 79 years and determined IR using the homeostasis model assessment of insulin resistance (HOMA-IR). The associations of HOMA-IR and other diabetic parameters per 1-SD increase with CAC prevalence and progression were evaluated using multivariable logistic regression. Of 1006 total participants at baseline (mean age, 64±10 years), CAC prevalence was observed in 646 (64.2%), and of 789 participants at follow-up (mean duration, 4.9±1.3 years), CAC progression was observed in 365 (46.3%). After adjustment for covariates including metabolic syndrome components, higher HOMA-IR was independently associated with CAC prevalence (adjusted odds ratio 1.34, 95% confidence interval 1.10-1.63; P=0.003) and progression (odds ratio 1.32, 95% confidence interval 1.09-1.60; P=0.004). In participants without diabetes mellitus, positive associations were similarly observed (prevalence: odds ratio 1.29, 95% confidence interval 1.04-1.60; P=0.022; and progression: odds ratio 1.25, 95% confidence interval 1.01-1.55; P=0.042), whereas glucose and hemoglobin A1c were not associated with CAC prevalence and progression. CONCLUSIONS: Higher IR was associated with CAC prevalence and progression independently of metabolic syndrome components in Japanese men and also in those without diabetes mellitus. Among diabetic measures, IR and fasting insulin, but not glucose and hemoglobin A1c, predicted CAC progression in men without diabetes mellitus.

DOI： 10.1161/atvbaha.116.307612

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

OBJECTIVE: The utility of lipoprotein particle profiles measured by nuclear magnetic resonance (NMR) spectroscopy beyond standard serum lipids remains inconclusive. Furthermore, few studies have compared NMR measurements with standard lipids in association with coronary artery calcification (CAC) in Japanese, where the coronary atherosclerotic burden is low. We examined whether NMR-based lipoprotein particle profiles are associated with CAC, and compared them with standard lipid and lipid ratios in the Japanese general population. METHODS AND RESULTS: We conducted a cross-sectional study in 851 men aged 40-79 years without cardiovascular diseases and lipid-lowering therapies. Adjusted odds ratios (ORs) (95% confidence intervals) for the top versus the bottom quartile of NMR-measured particle concentrations were 2.01 (1.24-3.23) for low-density lipoprotein (LDL-P), 1.04 (0.62-1.75) for high-density lipoprotein (HDL-P), 1.82 (1.13-2.95) for very-low-density lipoprotein (VLDL-P), and 1.92 (1.18-3.17) for LDL-P/HDL-P ratio. Similarly adjusted ORs of NMR-measured particle sizes were 0.59 (0.36-0.97) for LDL-P, 0.66 (0.40-1.10) for HDL-P, and 0.67 (0.40-1.12) for VLDL-P. The corresponding ORs were 1.82 (1.14-2.90) for total cholesterol (TC), 2.06 (1.28-3.30) for low-density lipoprotein cholesterol (LDL-C), 0.56 (0.34-0.91) for high-density lipoprotein cholesterol (HDL-C), 2.02 (1.24-3.29) for triglycerides, 2.08 (1.29-3.36) for non-high-density lipoprotein cholesterol (non-HDL-C), 2.27 (1.37-3.78) for TC/HDL-C ratio, and 1.73 (1.06-2.85) for LDL-C/HDL-C ratio. After mutual adjustment for total LDL-P concentration and TC/HDL-C ratio or non-HDL-C, LDL-P was no longer associated, whereas TC/HDL-C ratio remained significantly associated with CAC. CONCLUSIONS: In community-based Japanese men, the overall association of CAC with NMR-measured lipoprotein indices is comparable, but not superior, to that with standard lipids.

DOI： 10.1016/j.atherosclerosis.2014.07.019

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Background: Increased resting heart rate (RHR) independently predicts cardiovascular mortality. Meanwhile, long-chain n-3 fatty acids (LCn3FAs) have a cardioprotective effect. Our aim was to evaluate whether higher LCn3FAs intake attenuates the elevated risk of cardiovascular mortality associated with increased RHR.
Methods: We conducted a population-based 24-year prospective cohort study of Japanese, whose LCn3FAs intake is relatively high. Study participants included 8807 individuals aged 30-95 years from randomly selected areas across Japan without cardiovascular diseases and anti-hypertensive drugs at baseline. The primary endpoint was cardiovascular mortality, and the secondary endpoints were cardiac and stroke mortality during 24 years of follow-up. Individual dietary LCn3FAs intake was estimated from household-based 3-day weighed food records. RHR was obtained from 3 consecutive R-wave intervals on 12-lead electrocardiography. Cox models were used to estimate the multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) adjusting for possible confounders.
Results: During the follow-up period, 617 cardiovascular deaths were observed. The median daily intake of LCn3FAs was 0.37% kcal (0.86 g/day). The interaction between dietary LCn3FAs intake and RHR in the risk of cardiovascular mortality was statistically significant (p = 0.033). The risk of cardiovascular mortality was significantly higher in the low-intake group (&lt;0.37% kcal) with an RHR &gt;85 beats/min (bpm) [hazard ratio (HR), 1.67; 95% confidence interval (CI), 1.15-2.43], but not in the high-intake group (&gt;= 0.37% kcal) with an RHR &gt;85 bpm (HR, 0.92; 95% CI, 0.61-1.38), compared with those in the high-intake group with an RHR &lt;70 bpm. Similar results were observed with stroke mortality, but not with cardiac mortality.
Conclusions: The risk of cardiovascular mortality associated with increased RHR is elevated in participants with low dietary LCn3FAs intake, but not in participants with high dietary LCn3FAs intake in a representative Japanese general population. These results suggest that high dietary LCn3FAs intake may prevent cardiovascular mortality associated with increased RHR. (C) 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jjcc.2014.01.005

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMJ PUBLISHING GROUP  

Objective Higher marine-derived n-3 fatty acids (MDn3FAs) intake reduces the risk of sudden cardiac death via antiarrhythmic effects. The article evaluates whether MDn3FAs intake attenuates the increased risk of cardiac death associated with J-point elevation (JPE), characterised by an elevation of QRS-ST junction (J-point) &gt;= 0.1 mV on electrocardiography.
Design A prospective population-based cohort study.
Setting The National Survey on Circulatory Disorders and the National Nutrition Survey of Japan.
Participants A total of 4348 community-dwelling men (mean age 49.3 years), without cardiovascular diseases at baseline, from randomly selected areas across Japan.
Main outcome measures Cardiac death (200 men) during the 24-year follow-up.
Results Dietary MDn3FAs intake was assessed using a dietary method to estimate individual intake of household-based weighed food records for 3 days. Cox models were used to calculate HRs and 95% CIs adjusted for possible confounding factors. JPE was present in 340 participants (7.8%). The median daily intake of MDn3FAs was 0.35% kcal (0.92 g/day). The risk of cardiac death was significantly higher in participants with JPE than in those without JPE in the low intake group (&lt;0.35% kcal; adjusted HR 3.51; 95% CI 1.84 to 6.73; p&lt;0.001), but not in the high intake group (&gt;= 0.35% kcal; adjusted HR 1.09; 95% CI 0.56 to 2.16; p=0.795). The interaction between dietary MDn3FAs intake and JPE on the risk of cardiac death was statistically significant (p=0.006).
Conclusions The increased risk of cardiac death associated with JPE may be attenuated by higher dietary MDn3FAs intake.

DOI： 10.1136/heartjnl-2012-303496

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Authorship：Lead author,　Corresponding author  

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Heated tobacco products (HTPs) are nicotine-containing products similar to cigarettes and are widely used in Japan. However, there has been insufficient research on nicotine dependence associated with HTP use. This study investigated the association of the types of individuals who smoked with the prevalence of nicotine dependence. We utilized data from the Japan Survey on Tobacco and Health (JASTIS). A total of 7969 participants who currently smokes was selected from the 2022 and 2023 survey respondents for the analysis. Nicotine dependence was defined as a score of 5 or higher on the Tobacco Dependence Screener (TDS). The prevalence of nicotine dependence was 43.0% (3473/8077) among all participants who smoked, 42.9% (1479/3447) among those who used cigarettes, 44.2% (760/1720) among those who used two products, and 43.0% (1206/2802) among those who used HTPs. The prevalence of nicotine dependence was statistically higher in the participants who used two products than in cigarettes (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.04-1.33). When classified by temperature, participants who used of two products (high-temp and low-temp) and those using participants who used HTPs (high-temp) had higher ORs for prevalent nicotine dependence (OR, 1.31 [95% CI, 1.14-1.51]) and (OR, 1.12 [95% CI, 1.00-1.25], respectively) compared to participants who used cigarettes. Additionally, the ORs for prevalent nicotine dependence increased with the number of tobacco sticks smoked per day. These results suggest that HTP use, particularly high-temperature HTPs use, and a higher number of tobacco sticks smoked is associated with nicotine dependence.

DOI： 10.1002/npr2.12512

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AIMS: The variant in SCN5A with the loss of function (LOF) effect in the cardiac Na+ channel (Nav1.5) is the definitive cause for Brugada syndrome (BrS), and the functional analysis data revealed that LOF variants are associated with poor prognosis. However, which variant types (e.g. missense or non-missense) affect the prognoses of those variant carriers remain unelucidated. METHODS AND RESULTS: We defined SCN5A LOF variants as all non-missense and missense variants that produce peak INa < 65% of wild-type previously confirmed by patch-clamp studies. The study population consisted of 76 Japanese BrS patients (74% patients were male and the median age [IQR] at diagnosis was 28 [14-45] years) with LOF type of SCN5A variants: 40 with missense and 36 with non-missense variants. Non-missense variant carriers presented significantly more severe cardiac conduction disorder compared to the missense variant carriers. During follow-up periods of 9.0 [5.0-14.0] years, compared to missense variants, non-missense variants were significant risk factors of lifetime lethal arrhythmia events (LAEs) (P = 0.023). When focusing only on the missense variants that produce no peak INa, these missense variant carriers exhibited the same clinical outcomes as those with non-missense (log-rank P = 0.325). After diagnosis, however, both variant types were comparable in risk of LAEs (P = 0.155). CONCLUSION: We identified, for the first time, that SCN5A non-missense variants were associated with higher probability of LAE than missense variants in BrS patients though it did not change significantly after diagnosis.

DOI： 10.1093/europace/euaf024

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Authorship：Lead author,　Corresponding author   Language：English  

DOI： 10.1038/s41440-024-02064-0

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DOI： 10.1038/s41440-024-02039-1

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AIMS: Myotonic dystrophy Type 1 (DM1) is caused by the expansion of CTG repeats (CTGn) in the DM1 protein kinase (DMPK) gene, while it remains unclear whether CTGn may be associated with the incidence of cardiac events or sudden death in Japan as well as Europe. The aim of this study was to investigate the association between CTGn and cardiac involvements. METHODS AND RESULTS: This cohort study included patients with DM1 who were retrospectively recruited from nine Japanese hospitals specializing in neuromuscular diseases. A total of 496 patients with DM1 who underwent a genetic test in the DMPK gene were analysed. Patients with congenital form or under 15 years old were excluded and patients were assigned into the quartiles. When we compared the incidence of cardiac events including advanced/complete atrioventricular block, pacemaker implantation, and ventricular tachycardias or mortality among four groups, patients with 1300 or longer CTGn experienced composite cardiac events [hazard ratio (HR): 3.19, 95% confidence interval (CI): 1.02-9.99, P = 0.014] more frequently and had significantly higher mortality rate (HR: 6.79, 95% CI: 2.05-22.49, P < 0.001) than those under 400 CTGn while the rate of sudden death was not significantly different. CONCLUSION: Regarding the cardiac events and mortality in patients with DM1, patients with 1300 or longer CTGn are at especially high risk.

DOI： 10.1093/ehjopen/oeae078

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publisher：岡山医学会  

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The Shiga Epidemiological Study of Subclinical Atherosclerosis was conducted in Kusatsu City, Shiga, Japan, from 2006 to 2008. Participants were measured for LDL-p through nuclear magnetic resonance technology. 740 men participated in follow-up and underwent 1.5 T brain magnetic resonance angiography from 2012 to 2015. Participants were categorized as no-ICAS, and ICAS consisted of mild-ICAS (1 to < 50%) and severe-ICAS (≥ 50%) in any of the arteries examined. After exclusion criteria, 711 men left for analysis, we used multiple logistic regression to examine the association between lipid profiles and ICAS prevalence. Among the study participants, 205 individuals (28.8%) had ICAS, while 144 individuals (20.3%) demonstrated discordance between LDL-c and LDL-p levels. The discordance "low LDL-c-high LDL-p" group had the highest ICAS risk with an adjusted OR (95% CI) of 2.78 (1.55-5.00) in the reference of the concordance "low LDL-c-low LDL-p" group. This was followed by the concordance "high LDL-c-high LDL-p" group of 2.56 (1.69-3.85) and the discordance "high LDL-c-low LDL-p" group of 2.40 (1.29-4.46). These findings suggest that evaluating LDL-p levels alongside LDL-c may aid in identifying adults at a higher risk for ICAS.

DOI： 10.1038/s41598-024-59523-4

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BACKGROUND: Little is known regarding whether ultra-rapid patterns of heart rate variability (eg, heart rate fragmentation [HRF]) are associated with coronary artery calcification (CAC) in a general population. OBJECTIVES: This study aimed to assess the association between HRF and CAC, and whether these associations are independent of systolic blood pressure (SBP) levels. METHODS: From SESSA (the Shiga Epidemiological Study of Subclinical Atherosclerosis), we used data from 24-hour ambulatory blood pressure monitoring to identify awake and asleep SBP levels, and data from concurrent 24-hour Holter monitoring to quantify HRF using the awake and asleep percentage of inflection points (PIP). CAC on computed tomography scanning was quantified using an Agatston score. We used multivariable binomial logistic regression to assess the associations of PIP and ambulatory SBP with the presence of CAC, as defined by Agatston score >0. RESULTS: Of the 508 participants in this study (mean age: 66.5 ± 7.3 years), 325 (64%) had CAC and 183 (36%) did not. In fully adjusted models of prevalent CAC that also included office SBP, the ORs with 95% CIs for awake PIP, awake SBP, asleep PIP, and asleep SBP were 1.23 (95% CI: 0.99-1.54), 1.40 (95% CI: 1.11-1.77), 1.31 (95% CI: 1.05-1.62), and 1.28 (95% CI: 1.02-1.60), respectively. There was no evidence of interaction between PIP and ambulatory SBP in association with CAC. Results were similar when other HRF indices instead of PIP were used. CONCLUSIONS: Higher HRF and SBP levels during sleep are each associated with the presence of CAC in a general male population.

DOI： 10.1016/j.jacasi.2023.10.004

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BACKGROUND: Deviations of hemoglobin from normal levels may be a factor in cardiovascular disease (CVD) risk; however, conclusive evidence is lacking. In addition, preclinical conditions may influence hemoglobin concentrations, but studies focusing on reverse causation are limited. Thus, we examined the relationship between hemoglobin concentrations and CVD mortality risk, considering reverse causation.Methods and Results: In a prospective cohort representative of the general Japanese population (1990-2015), we studied 7,217 individuals (mean age 52.3 years; 4,219 women) without clinical CVD at baseline. Participants were categorized into sex-specific hemoglobin quintiles (Q1-Q5) and data were analyzed using the Cox proportional hazards model adjusted for possible confounders. During a 25-year follow-up, 272 men and 334 women died from CVD. Adjusted hazard ratios for CVD mortality across sex-specific quintiles, using Q3 as the reference, were significantly higher for Q1 (1.40; 95% confidence interval [CI] 1.08-1.82) and Q5 (1.49; 95% CI 1.14-1.96), and remained significant after excluding deaths within the first 5 years of follow-up to consider reverse causation (1.35 [95% CI 1.02-1.79] and 1.45 [95% CI 1.09-1.94], respectively). A similar U-shaped association was seen between transferrin saturation levels and CVD mortality, but after excluding deaths within the first 5 years the association was significant only for Q1. CONCLUSIONS: Low and high hemoglobin concentrations were associated with an increased risk of CVD mortality.

DOI： 10.1253/circj.CJ-23-0725

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BACKGROUND: Increasing physical activity may prevent cognitive decline. Previous studies primarily focused on older adults and used self-reported questionnaires to assess physical activity. We examined the relationship between step count, an objective measure of physical activity, and cognitive function in community-based middle-aged and older Japanese men. METHODS: The Shiga Epidemiological Study of Subclinical Atherosclerosis randomly recruited community-dwelling healthy men aged 40-79 years from Shiga, Japan, and measured their step counts over 7 consecutive days using a pedometer at baseline (2006-2008). Among men who returned for follow-up (2009-2014), we assessed their cognitive function using the Cognitive Abilities Screening Instrument (CASI) score. We restricted our analyses to those with valid 7-day average step counts at baseline and those who remained free of stroke at follow-up (n = 676). Using analysis of covariance, we calculated the adjusted means of the CASI score according to the quartiles of the average step counts. RESULTS: The mean (standard deviation) of age and unadjusted CASI score were 63.8 (9.1) years and 90.8 (5.8), respectively. The CASI score was elevated in higher quartiles of step counts (90.2, 90.4, 90.6, and 91.8 from the lowest to the highest quartile, respectively, [p for trend = 0.004]) in a model adjusted for age and education. Further adjustment for smoking, drinking, and other cardiovascular risk factors resulted in a similar pattern of association (p for trend = 0.005). CONCLUSION: In apparently healthy middle-aged and older Japanese men, a greater 7-day average step count at baseline was associated with significantly higher cognitive function score.

DOI： 10.1016/j.pmedr.2024.102615

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Language：Japanese   Publisher：(一社)日本疫学会  

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DOI： 10.1038/s41440-023-01488-4

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BACKGROUND: The gut microbiota differs between patients with coronary artery disease (CAD) and healthy controls; however, it currently remains unclear whether these differences exist prior to the onset of CAD. We herein investigated the gut microbiota associated with subclinical coronary artery calcification (CAC) in a Japanese population. METHODS: A total of 663 Japanese men were enrolled in this cross-sectional study. Computed tomography and gut microbiology tests were performed, and CAC scores were calculated using the Agatston method. Participants were categorized into four groups based on their CAC scores: CAC = 0, 0 <CAC ≤100, 100 <CAC, and with a CAD history. The bacterial 16S ribosomal RNA gene was amplified, and DNA sequencing was conducted on a MiSeq System. QIIME2 and LEfSe were used to analyze the gut microbiota, and the results obtained were compared among the four CAC categories. RESULTS: The mean age of participants was 68.4 years (46-83 years). The numbers of participants in CAC = 0, 0 <CAC ≤100, 100 <CAC, and with a CAD history were 219, 200, 193, and 51, respectively. The medians of the Firmicutes to Bacteroidota ratio were 1.50, 1.52, 1.67, and 1.80 for each CAC category (P = 0.020). One standard deviation higher phylum Firmicutes, class Bacilli, and order Lactobacillales were associated with a 1.3- to 1.4-fold higher risk of CAD. These taxa were also associated with a higher CAC score category. The family Streptococcaceae and genus Streptococcus showed a higher risk of CAD. The order Enterobacterales and family Enterobacteriaceae correlated with CAC scores. The genus Blautia showed a preventive direction for CAD, but did not correlate with CAC scores. CONCLUSIONS: The gut microbiota significantly differed from the phylum to genus level in a manner that was dependent on CAC scores, even before the onset of CAD.

DOI： 10.1016/j.ahj.2023.09.009

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DOI： 10.1253/circj.CJ-23-0590

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BACKGROUND: Internet addiction (IA) has been drawing attention to mental health. However, few reports have been found on the related factors of at-risk IA among regular workers by a nationwide survey. The study aimed to evaluate the characteristics of at-risk IA and identify related factors among senior high school teachers in Japan. METHODS: This survey was a cross-sectional survey of high schools across Japan in 2017. There were 3189 teachers (2088 males and 1098 female) who participated in this survey. The questionnaire asked about their devices, both the time and the activities of using their internet, and sociodemographic factors. IA was measured by the internet addiction test (IAT) by which 40-79 points were classified as at-risk IA, and more as IA. We compared the related factors of at-risk IA and non-IA using descriptive analysis and multivariable regression analysis. RESULTS: The rates of IA and at-risk IA were 0.09% (n = 3) and 6.91% (n = 220), respectively. At-risk IA was positively associated with activities on the internet for gaming, entertainment, net-surfing, and younger ages. In addition, the at-risk IA group had a longer time spent on the internet than the non-IA group. CONCLUSIONS: Around 7% of high school teachers are at-risk IA in this survey, though they have regular work. Our results suggest that at-risk IA may be reinforced not only by the active internet use such as gaming, but also by purposeless behaviors, such as net-surfing. Managing time on the internet may support preventing at-risk IA among senior high school teachers.

DOI： 10.1002/npr2.12350

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Rapid eating has been demonstrated to be associated with obesity and overweight. However, few studies have characterized the separate relationships of eating speed with visceral and subcutaneous fat mass or circulating adiponectin concentration. We hypothesized that rapid eating is associated with the larger visceral fat tissue (VFT) area and lower adiponectin concentration, but not with the subcutaneous fat tissue (SFT) area in men and women. We performed a cross-sectional study of 712 adults aged 20-86 years (528 men and 184 women; mean ± SD age 59.36 ± 13.61 years). The participants completed a self-reported questionnaire, and underwent anthropometric and laboratory measurements and computed tomographic imaging of the abdomen as a part of annual medical check-ups. Multivariate linear regression analyses revealed that rapid eating was associated with larger visceral (B = 24.74; 95% CI 8.87-40.61, p = 0.002) and subcutaneous fat areas (B = 31.31; 95% CI 12.23-50.38, p = 0.001), lower adiponectin concentration (B =  - 2.92; 95% CI - 4.39- - 1.46, p < 0.001), higher body mass index (BMI) (B = 2.13; 95% CI 1.02-3.25, p < 0.001), and larger waist circumference (B = 5.23; 95% CI 2.16-8.30, p < 0.001) in men, which is partially consistent with the hypothesis. In contrast, rapid eating was found to be associated only with BMI, and not with abdominal adipose area or adiponectin concentration in women, which is a result that is not consistent with the hypothesis. These results suggest that there is no difference in the association of rapid eating with VFT and SFT areas.

DOI： 10.1038/s41598-023-38623-7

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Coronary artery calcium (CAC), which is detected using computed tomography scanning, is a well-established indicator of subclinical atherosclerosis. The CAC score is independently associated with atherosclerotic cardiovascular disease (ASCVD) outcomes and provides improved predictive values for estimating the risk of ASCVD beyond traditional risk factors. Thus, CAC is considered to have important implications for reclassification as a decision aid among individuals in the preclinical phase and as the primary prevention of ASCVD. This review is focused on epidemiological evidence on CAC in asymptomatic population-based samples from Western countries and Japan. We also discuss the usability of CAC as a tool for assessing ASCVD risk and its role in the primary prevention of ASCVD. A lack of evidence for the CAC score in ASCVD risk assessment beyond traditional risk factors in populations other than those in Western countries (including Japan) warrants further investigation. Clinical trials are also necessary to demonstrate the usefulness and safety of CAC screening in the primary prevention of ASCVD.

DOI： 10.5551/jat.RV22009

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Background Little is known regarding whether arterial stiffness and atherosclerotic burden are each independently associated with brain structural changes. Simultaneous assessments of both arterial stiffness and atherosclerotic burden in associations with brain could provide insights into the mechanisms of brain structural changes. Methods and Results Using data from the SESSA (Shiga Epidemiological Study of Subclinical Atherosclerosis), we analyzed data among 686 Japanese men (mean [SD] age, 67.9 [8.4] years; range, 46-83 years) free from history of stroke and myocardial infarction. Brachial-ankle pulse wave velocity and coronary artery calcification on computed tomography scans were measured between March 2010 and August 2014. Brain volumes (total brain volume, gray matter, Alzheimer disease signature and prefrontal) and brain vascular damage (white matter hyperintensities) were quantified using brain magnetic resonance imaging from January 2012 through February 2015. In multivariable adjustment models including mean arterial pressure, when brachial-ankle pulse wave velocity and coronary artery calcification were entered into the same models, the β (95% CI) for Alzheimer disease signature volume for each 1-SD increase in brachial-ankle pulse wave velocity was -0.33 (-0.64 to -0.02), and the unstandardized β (95% CI) for white matter hyperintensities for each 1-unit increase in coronary artery calcification was 0.68 (0.05-1.32). Brachial-ankle pulse wave velocity and coronary artery calcification were not statistically significantly associated with total brain and gray matter volumes. Conclusions Among Japanese men, higher arterial stiffness was associated with lower Alzheimer disease signature volumes, whereas higher atherosclerotic burden was associated with brain vascular damage. Arterial stiffness and atherosclerotic burden may be independently associated with brain structural changes via different pathways.

DOI： 10.1161/JAHA.122.028586

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Authorship：Lead author,　Last author,　Corresponding author   Language：English  

DOI： 10.4070/kcj.2023.0075

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AIMS: More than one-third of type 2 long QT syndrome (LQT2) patients carry KCNH2 non-missense variants that can result in haploinsufficiency (HI), leading to mechanistic loss-of-function. However, their clinical phenotypes have not been fully investigated. The remaining two-thirds of patients harbour missense variants, and past studies uncovered that most of these variants cause trafficking deficiency, resulting in different functional changes: either HI or dominant-negative (DN) effects. In this study, we examined the impact of altered molecular mechanisms on clinical outcomes in LQT2 patients. METHODS AND RESULTS: We included 429 LQT2 patients (234 probands) carrying a rare KCNH2 variant from our patient cohort undergoing genetic testing. Non-missense variants showed shorter corrected QT (QTc) and less arrhythmic events (AEs) than missense variants. We found that 40% of missense variants in this study were previously reported as HI or DN. Non-missense and HI-groups had similar phenotypes, while both exhibited shorter QTc and less AEs than the DN-group. Based on previous work, we predicted the functional change of the unreported variants-whether they cause HI or DN via altered functional domains-and stratified them as predicted HI (pHI)- or pDN-group. The pHI-group including non-missense variants exhibited milder phenotypes compared to the pDN-group. Multivariable Cox model showed that the functional change was an independent risk of AEs (P = 0.005). CONCLUSION: Stratification based on molecular biological studies enables us to better predict clinical outcomes in the patients with LQT2.

DOI： 10.1093/europace/euac269

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BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new target for reducing low-density lipoprotein cholesterol (LDL-C) and incident cardiovascular disease, including stroke. However, the clinical relevance of circulating PCSK9 levels have been poorly elucidated in the general population, particularly in association with subclinical cerebrovascular disease including cerebral small vessel disease (CSVD) and intracranial artery stenosis (ICAS). METHODS: In community-dwelling Japanese men (n = 526) aged 46-82 years without a history of cardiovascular disease, we assessed the associations of serum PCSK9 levels with the prevalence of CSVD and ICAS using magnetic resonance imaging. CSVD included lacunar infarction, deep and subcortical white matter hyperintensity, periventricular hyperintensity, and cerebral microbleeds. RESULTS: The median (interquartile range) age at baseline and serum PCSK9 levels were 69 (63 - 74) years and 240 (205-291) ng/mL, respectively. After adjusting for traditional cardiovascular risk factors including LDL-C, multivariable Poisson regression with robust error variance revealed a significant association between PCSK9 levels (per 1-SD) and ICAS (relative risks 1.18, 95% confidence intervals [CI] 1.02-1.37). Multivariable ordinal logistic regression for ICAS, with stenosis graded as mild (<50%) or moderate-severe (≥50%), revealed a similar association (common odds ratio 1.31, 95% CI 1.04-1.64). However, no significant association was observed between serum PCSK9 levels and CSVD. CONCLUSIONS: Higher circulating PCSK9 levels were independently associated with a ICAS prevalence but not with a CSVD prevalence. The quantification of circulating PCSK9 levels may help to identify individuals at high risk for cerebrovascular disease in the general population.

DOI： 10.1111/ene.15723

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BACKGROUND: Underage drinking is a public health concern. However, few studies have examined the association between alcoholic beverage advertising and underage drinking, particularly in countries with low underage drinking rates, such as Japan. Therefore, we aimed to investigate the relationship between exposure to advertising in various media and alcohol drinking among Japanese adolescents. METHODS: We conducted a cross-sectional study involving 15,683 adolescents (51% girls) using data from a nationwide lifestyle survey in 2021 among junior and senior high schools across Japan. Media types were websites, stores, and public transportation. We defined current drinking as alcohol consumption of ≥1 day in the 30 days preceding the survey. Multivariable logistic regression was used to examine the association between exposure to alcohol advertisements and current drinking, adjusting for sex, grades, school area, lifestyle (bedtime and having fun at school), and addictive behaviors (smoking status and parents' alcohol consumption). RESULTS: The prevalence of current drinking was 2.2% (2.3% of boys and 2.0% of girls). Students who were exposed to any alcohol advertising media had higher odds of current drinking compared with those who were not (odds ratio, 1.48; 95% confidence interval [CI], 1.18-1.87). Students who were exposed to web, in-store, and public transportation advertisements had odds ratios of 1.44 (95% CI, 1.14-1.81), 1.62 (1.28-2.05), and 1.45 (1.06-1.98) of current drinking, respectively, compared with those who were not. The association of exposure to alcohol advertising media with the prevalence of current drinking was similar among boys and girls (all p for sex interaction >0.1), except for that of exposure to web advertisements; its association with current drinking was more pronounced in girls (p for sex interaction = 0.046). Exposure to a larger cumulative number of different alcohol advertising media was independently associated with a higher prevalence of current drinking among all students, boys, and girls (p-values for trend <0.001, 0.031, and <0.001, respectively; p for sex interaction = 0.085). CONCLUSIONS: We found an association with a dose-response relationship between exposure to alcohol advertisements and current drinking among adolescents in junior and senior high schools across Japan. Our findings highlight the need for further advertising regulations to prevent underage drinking.

DOI： 10.1265/ehpm.23-00127

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Equol is an isoflavone (ISF)-derived metabolite by the gut microbiome in certain individuals termed equol-producers (EP). Equol might be the critical anti-atherogenic component of ISFs. In a population-based study of 979 Japanese men aged 40-79 without cardiovascular (CVD) or chronic kidney disease, we measured the urinary levels of equol and ISFs. Aortic calcification (AC) in the entire aorta was assessed by electron-beam or multi-detector-row computed tomography. Subjects with log10 (urinary equol to daidzein concentration) > - 1.5 were classified as EP. EP was further classified as person with low- and high-equol. We analyzed the association between equol-producing status and AC presence, defined as AC score > 0, by the logistic regressions. We found that EP (50% of the sample) had significantly lower odds of AC presence (odds ratio (OR): 0.62, 95% confidence interval (CI): 0.39, 0.98) compared to non-EP. This association was independent of CVD risk factors. For the dose-response association, compared to non-EP, subjects with low and high levels of equol had ORs of 0.51 (95% CI 0.30, 0.84) and 0.67 (95% CI 0.39, 1.14) after adjusting for major CVD risk factors (p for trend = 0.06). ISFs concentrations were not significantly associated with AC presence (OR: 1.18, 95% CI: 0.82, 1.69). In conclusion, EP had a significantly lower burden of AC than non-EP, while ISFs were not associated with AC presence in Japanese men aged 40-79 years.

DOI： 10.1038/s41598-022-24659-8

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AIM: Irisin, an exercise-induced myokine, is a potential neurotrophic factor; however, its relationship with cerebral small vessel disease (CSVD) remains unknown. Therefore, we investigated whether serum irisin levels are associated with CSVD in healthy Japanese men. METHODS: We analyzed data from 720 men free of stroke and participated in this observational study. Serum irisin levels were measured by enzyme-linked immunosorbent assay. CSVD was assessed on deep and subcortical white matter hyperintensities (DSWMHs), periventricular hyperintensities (PVHs), lacunar infarcts (LIs), and cerebral microbleeds (CMBs) on brain magnetic resonance imaging. We calculated the total CSVD score (ranges 0-4) to express the total CSVD burden. We computed the adjusted odds ratios (ORs), with 95% confidence intervals (CIs), of the total CSVD score and individual CSVD features using logistic regression models according to the quartiles of irisin (reference: Q1). RESULTS: Serum irisin levels were associated with lower ORs of higher (vs. zero or lower score) total CSVD score, with the lowest risk (OR, 0.63; 95% CI, 0.41-0.97) being observed in Q3 compared to Q1 after adjustment of potential covariates. Similar results were obtained for younger adults (＜65 years). Among individual CSVD features, irisin was associated with a reduced risk of LIs in the total sample and PVHs, LIs, and CMBs in younger adults. No relationship was observed in older adults (≥ 65 years). CONCLUSIONS: Serum irisin levels were associated with less burden of total CSVD in healthy Japanese men. Serum irisin levels were also related with a reduced risk of PVHs, LIs, and CMBs, but not DSWMHs.

DOI： 10.5551/jat.63824

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AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for reducing low-density lipoprotein cholesterol (LDL-C) and cardiovascular events in high-risk patients. However, the influence of circulating PCSK9 concentration on atherosclerotic plaque formation in the general population remains unknown. We assessed the relationship between serum PCSK9 concentration and coronary artery calcium (CAC) prevalence in the general population. METHODS: Community-dwelling Japanese men (n=622) aged 46-82 years without a history of cardiovascular disease and lipid-lowering medications were included. Serum PCSK9 concentration and CAC score were measured using the Agatston method, and the multivariable analysis was used to assess their association. CAC was defined as an Agatston score of ＞10. We conducted further analysis stratified by age (＜60, 60-69, and ≥ 70 years). RESULTS: The average age, LDL-C, and median serum PCSK9 concentration were 68 years, 122 mg/dL, and 240 ng/mL, respectively. After multivariable adjustment for traditional cardiovascular risk factors, no significant association was observed between serum PCSK9 concentration and CAC prevalence (adjusted relative risk [aRR] 1.05, 95% confidence interval [CI] 0.97-1.13). With age stratification, serum PCSK9 concentration was significantly associated with CAC prevalence in men aged ＜60 years (aRR 1.38, 95% CI 1.01-1.88) but not in men aged 60-69 years (aRR 0.96, 95% CI 0.85-1.10) or ≥ 70 years (aRR 1.08, 95% CI 0.99-1.19). CONCLUSIONS: A higher serum PCSK9 concentration was associated with a higher CAC prevalence in men aged ＜60 years, which was independent of traditional cardiovascular risk factors.

DOI： 10.5551/jat.63549

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The relation between chronic kidney disease (CKD) and cardiovascular disease (CVD) in the general population is well elucidated. In patients with CKD, anemia is associated with adverse outcomes. However, the effects of CKD and anemia on CVD in the general population remains poorly explored, especially in Asian populations. This study aimed to investigate the effect of CKD and/or anemia on CVD mortality in a long-term cohort study involving Japanese community dwellers. We assessed 7,339 participants (aged ≥30 years) with no CVD history. These participants were divided into 4 categories according to their CKD (estimated glomerular filtration rate <60 or urine protein >1+ by dipstick qualitative test) and/or anemia (hemoglobin: <13 g/100 ml [men], <12 g/100 ml [women]) statuses. For each category, we calculated the hazard ratios (HRs) of CVD mortality by using the Cox proportional hazards model after adjusting for age, body mass index, hypertension, diabetes, dyslipidemia, smoking, and alcohol drinking. Within 25 years of follow-up, 637 participants died because of CVD. The HRs of CVD in patients with CKD only, anemia only, and both were 1.27, 1.59, and 2.60 (95% confidence intervals [CI] 1.06 to 1.53, 1.34 to 1.90, and 1.80 to 3.76) in men and 1.42, 1.08, and 2.00 (95% CI 1.19 to 1.69, 0.99 to 1.18, and 1.54 to 2.60) in women, respectively. In conclusion, CKD with anemia is associated with an increased risk for CVD mortality in a general population in Japan.

DOI： 10.1016/j.amjcard.2022.08.027

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BACKGROUND: An association between a high intake of marine-derived n-3 polyunsaturated fatty acids (n-3 PUFAs) with a lower risk of coronary heart disease was previously reported. However, the association between n-3 PUFAs and cerebrovascular lesions remains unclear. We evaluated this association in a general-population-based sample of Japanese men. METHODS: Participants were community-dwelling men (40-79 years old) living in Kusatsu City, Shiga, Japan. Serum concentrations of n-3 PUFAs, defined as the sum of eicosapentaenoic and docosahexaenoic acids, were measured via gas-liquid chromatography between 2006 and 2008. Magnetic resonance imaging was used to assess cerebrovascular lesions (including intracerebral large-artery stenosis, lacunar infarction, and microbleeds) and white matter lesions between 2012 and 2015. Logistic regression adjusting for conventional cardiovascular risk factors was used to estimate the odds ratio of prevalent cerebrovascular lesions per 1 standard deviation higher serum concentration of n-3 PUFAs. RESULTS: Of a total of 739 men, the numbers (crude prevalence in %) of prevalent cerebral large-artery stenoses, lacunar infarctions, microbleeds, and white matter lesions were 222 (30.0), 162 (21.9), 103 (13.9), and 164 (22.2), respectively. A 1 standard deviation higher concentration of n-3 PUFAs (30.5 μmol/L) was independently associated with lower odds of cerebral large-artery stenosis (multivariable-adjusted odds ratio, 0.80; 95% confidential interval, 0.67-0.97). There were no significant associations of n-3 PUFAs with the other types of lesions. CONCLUSIONS: n-3 PUFAs may have protective effects against large-artery stenosis, but not small vessel lesions, in the brain.

DOI： 10.1159/000524243

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Authorship：Lead author,　Corresponding author   Language：English   Publisher：Nature Publishing Group  

DOI： 10.1038/s41440-021-00844-6

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J04682&link_issn=&doc_id=20220310180018&doc_link_id=10.1038%2Fs41440-021-00844-6&url=https%3A%2F%2Fdoi.org%2F10.1038%2Fs41440-021-00844-6&type=Crossref&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00002_2.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本循環器学会  

BACKGROUND: Premature atrial contractions (PACs) are predictors of atrial fibrillation, stroke, and cardiovascular mortality. The present study aimed to assess relevant factors for PACs among a general population of Japanese men.Methods and Results:This study conducted a population-based, cross-sectional study among 517 men, aged 40-79 years, with neither apparent myocardial infarction nor atrial fibrillation. 24-h Holter electrocardiography to assess PAC frequency was used. Age, body mass index, height, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol, mean heart rate, diabetes mellitus, hypertension, physical activity, smoking, alcohol consumption, and lipid-lowering therapy were included in multivariable negative binomial regression analyses to assess correlation for the number of PACs per hour. Almost all participants (99%) had at least 1 PAC in 1 h (median number 2.84 PACs per h). In multivariable negative binomial regression after adjusting for all covariates simultaneously, age (relative risk [95% confidence interval], 1.30 [1.08-1.57] per 1-standard deviation [SD] increment), height (1.19 [1.02-1.39] per 1-SD increment), triglycerides (0.79 [0.65-0.97] per 1-SD increment), mean heart rate (0.69 [0.59-0.80] per 1-SD increment), physical activity (0.63 [0.43-0.93]), current smoking (1.69 [1.06-2.69]), current moderate (1.97 [1.23-3.16]) and heavy (1.84 [1.12-3.01]) alcohol consumption were independently associated with PAC frequency. CONCLUSIONS: PAC frequency was independently associated with age, height, smoking, alcohol consumption, heart rate, physical activity, and triglycerides.

DOI： 10.1253/circj.CJ-21-0872

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J04756&link_issn=&doc_id=20220817400013&doc_link_id=10.1253%2Fcircj.CJ-21-0872&url=https%3A%2F%2Fdoi.org%2F10.1253%2Fcircj.CJ-21-0872&type=Crossref&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00002_2.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Atherosclerosis Society  

AIMS: The roles of urinary albumin, eGFRcystatin (eGFRcys), and eGFRcreatinine (eGFRcre) in the progression of coronary artery calcification (CAC) remain unclear. Therefore, the present study investigated the relationship between kidney function and CAC progression. METHODS: A total of 760 Japanese men aged 40-79 years were enrolled in this population-based study. Kidney function was measured using eGFRcre, eGFRcys, and the urine albumin-to-creatinine ratio. CAC scores were calculated using the Agatston method. CAC progression was defined as an annual increase of ＞10 Agatston units (AU) among men with 0＜CAC＜100 AU at baseline, that of ＞10% among those with CAC ≥ 100 AU, and any progression for those with CAC=0 at baseline. The relative risk (RR) of CAC progression based on kidney function was assessed using a robust Poisson regression model. RESULTS: The mean follow-up period was 4.9 years. CAC progression was detected in 45.8% of participants. Positive associations between CAC progression and albuminuria (＞30mg/g) (RR: 1.29; 1.09 to 1.53; p=0.004) and low eGFRcys (＜60ml/min/1.73m2) (RR: 1.27; 1.05 to 1.53; p=0.012) remained significant after adjustments for age, the follow-up time, and computerized tomography type. Following further adjustments for hypertension, diabetes mellitus, dyslipidemia, C-reactive protein, and lifestyle factors, CAC progression was associated with albuminuria (RR: 1.20; 1.01 to 1.43; p=0.04) and low eGFRcys (RR: 1.19; 0.99 to 1.43; p=0.066), but not with eGFRcre. CONCLUSION: CAC progression was associated with albuminuria; however, its relationship with eGFRcys was weakened by adjustments for risk factors.

DOI： 10.5551/jat.63030

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1038/s41371-021-00589-2

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Other Link： http://www.nature.com/articles/s41371-021-00589-2

Language：English   Publisher：(一社)日本循環器学会  

BACKGROUND: Risk factors for atherosclerotic disease including dyslipidemia have been shown to be associated with aortic valve calcification (AVC). Nuclear magnetic resonance (NMR)-measured lipoprotein particles, low-density and high-density lipoprotein particles (LDL-p, HDL-p) in particular, have emerged as novel markers of atherosclerotic disease; however, whether NMR-measured particles are associated with AVC remains to be determined. This study aimed to examine the association between NMR-based lipoprotein particle measurements and standard lipids with AVC. The primary variables of interest were LDL-p (nmol/L), HDL-p (μmol/L), LDL-cholesterol, and HDL-cholesterol (both in mg/dL).Methods and Results:A community-based random sample of Japanese men aged 40-79 years examined in 2006-2008, in Shiga, Japan was studied. Presence of AVC was defined as an Agatston score >0. Lipoprotein particles were measured using NMR spectroscopy. In the main analysis, multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for the prevalence of AVC across the higher quartiles of lipids in reference to the lowest ones were obtained. Of 874 participants analyzed, 153 men had AVC. Multivariable-adjusted ORs of prevalent AVC for the highest vs. the lowest quartile were significantly elevated for LDL-p (OR, 2.20; 95% CI: 1.23-3.93) and LDL-cholesterol (OR, 2.16; 95% CI: 1.23-3.78). In contrast, neither HDL-p nor HDL-cholesterol was associated with AVC. CONCLUSIONS: The association of prevalent AVC with NMR-based LDL-p was comparable to that with LDL-cholesterol.

DOI： 10.1253/circj.CJ-20-1090

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Authorship：Lead author,　Last author,　Corresponding author   Language：English   Publisher：Japan Atherosclerosis Society  

DOI： 10.5551/jat.ed150

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DOI： 10.1016/j.jjcc.2020.09.008

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Language：English   Publisher：Japan Atherosclerosis Society  

AIMS: The utility of carotid intima-media thickness (cIMT) as a marker for coronary heart disease is under heavy debate. This is predominantly due to the lack of a standard definition of cIMT, leading to inconsistent results. We investigated and compared the relationships of five different measures of cIMT with coronary calcium. METHODS: Japanese men aged 40-79y (n=869) from Shiga Epidemiological Study of Subclinical Atherosclerosis were examined. Mean cIMT was measured in three segments of the carotid arteries: common carotid artery (CCAmean), internal carotid artery (ICAmean) and bifurcation (Bifmean). Mean cIMT of average values (Mean cIMT) and mean cIMT of maximum values (Mean-Max cIMT) of all segments combined were assessed. Coronary calcium was assessed as coronary artery calcification (CAC). Ordinal logistic regression was used to determine the odds ratio (OR) of higher CAC per 1 standard deviation higher cIMT measure. Analyses were adjusted for cardiovascular covariates and stratified by age quartiles. RESULTS: All cIMT measures had positive associations with CAC (p＜0.001): [OR, 95% Confidence Interval]: ICAmean [1.23, 1.07-1.42], CCAmean [1.27, 1.08-1.49], Bifmean [1.33, 1.15-1.53], Mean cIMT [1.42, 1.22-1.66], and Mean-Max [1.50, 1.28-1.75]. In age-stratified analyses, only Mean-Max cIMT maintained a significant relationship with CAC in every age quartile (p＜0.05), while CCAmean had some of the weakest associations among age quartiles. CONCLUSIONS: Mean-Max cIMT had consistently stronger associations with coronary calcium, independent of important confounders, such as age. The most oft-used measure, CCAmean, was no longer associated with coronary calcium after age-adjustment and stratification.

DOI： 10.5551/jat.61283

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The clinical implications of alcohol consumption have been extensively examined; however, its effects on brain structures in apparently healthy community-dwellers remain unclear. Therefore, we investigated the relationship between alcohol consumption and brain gray matter volume (GMV) in community-dwelling Japanese men using voxel-based morphometry (VBM). We recruited cognitively intact Japanese men, aged 40–79 years, from a population-based cohort in Shiga, Japan. Brain magnetic resonance imaging was performed, on average, 2 years after demographic and medical information was obtained in 2010–2014. A multivariable linear regression analysis of 639 men was conducted to elucidate the relationship between the amount of alcohol consumed and GMV. VBM statistics were analyzed by threshold-free cluster enhancement with a family-wise error rate of <0.05. The results obtained demonstrated that the amount of alcohol consumed was associated with lower GMV. The VBM analysis showed lower GMV within the parahippocampal, entorhinal, cingulate, insular, temporal, and frontal cortices and cerebellum in very heavy drinkers (≥42 ethanol g/day) than in non-drinkers. Furthermore, alcohol consumption was associated with a higher white matter lesion volume. These results suggest subclinical structural changes similar to alcohol-related neurological diseases.

DOI： 10.1016/j.alcohol.2020.11.006

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Human Kinetics  

BACKGROUND: To investigate the association between step counts and brain volumes (BVs)-global and 6 a priori selected cognition-related regions of interest-in Japanese men aged 40-79 years. METHODS: The authors analyzed data from 680 cognitively intact participants of the Shiga Epidemiological Study of Subclinical Atherosclerosis-a population-based observational study. Using multivariable linear regression, the authors assessed cross-sectional associations between 7-day step counts at baseline (2006-2008) and BVs at follow-up (2012-2015) for age-stratified groups (<60 y and ≥60 y). RESULTS: In the older adults ≥60 years, step counts at baseline (per 1000 steps) were associated with total BV at follow-up (β = 1.42, P = .022) while adjusted for potential covariates. Regions of interest-based analyses yielded an association of step counts with both prefrontal cortexes (P < .05) in older adults, while the left entorhinal cortex showed marginally significant association (P = .05). No association was observed with hippocampus, parahippocampal, cingulum, and cerebellum. No association was observed in younger adults (<60 y). CONCLUSIONS: The authors found a positive association between 7-day step counts and BVs, including prefrontal cortexes, and left entorhinal cortex in apparently healthy Japanese men.

DOI： 10.1123/jpah.2019-0659

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Other Link： https://journals.humankinetics.com/downloadpdf/journals/jpah/aop/article-10.1123-jpah.2019-0659/article-10.1123-jpah.2019-0659.xml

Language：English   Publisher：Springer Science and Business Media LLC  

Conventional office blood pressure (OBP) and home blood pressure (HBP) measurements are often inconsistent. The purpose of this research was (1) to test whether strictly measured OBP values with sufficient rest time before measurement (st-OBP) is comparable to HBP at the population level and (2) to ascertain whether there are particular determinants for the difference between HBP and st-OBP at the individual level. Data from a population-based group of 1056 men aged 40-79 years were analyzed. After a five-min rest, st-OBP was measured twice. HBP was measured after a 2-min rest every morning for seven consecutive days. To determine factors related to ΔSBP (HBP minus st-OBP measurements), multiple linear regression analyses and analyses of covariance were performed. While st-OBP and HBP were comparable (136.5 vs. 137.2 mmHg) at the population level, ΔSBP varied with a standard deviation of 13.5 mmHg. Smoking was associated with a larger ΔSBP regardless of antihypertensive usage, and BMI was associated with a larger ΔSBP in participants using antihypertensive drugs. The adjusted mean ΔSBP in the highest BMI tertile category was 4.6 mmHg in participants taking antihypertensive drugs. st-OBP and HBP measurements were comparable at the population level, although the distribution of ΔSBP was considerably broad. Smokers and obese men taking antihypertensive drugs had higher HBP than st-OBP, indicating that their blood pressure levels are at risk of being underestimated. Therefore, this group would benefit from the addition of HBP measurements.

DOI： 10.1038/s41440-020-00533-w

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Other Link： http://www.nature.com/articles/s41440-020-00533-w

Language：English   Publisher：Springer Science and Business Media LLC  

Despite the clinical usefulness of self-measured home blood pressure (BP), reports on the characteristics of home BP have not been sufficient and have varied due to the measurement conditions in each study. We constructed a database on self-measured home BP, which included five Japanese general populations as subdivided aggregate data that were clustered and meta-analyzed according to sex, age category, and antihypertensive drug treatment at baseline (treated and untreated). The self-measured home BPs were collected after a few minutes of rest in a sitting position: (1) the morning home BP was measured within 1 h of waking, after urination, before breakfast, and before taking antihypertensive medication (if any); and (2) the evening home BP was measured just before going to bed. The pulse rate was simultaneously measured. Eligible data from 2000 onward were obtained. The morning BP was significantly higher in treated participants than in untreated people of the same age category, and the BP difference was more marked in women. Among untreated residents, home systolic/diastolic BPs measured in the morning were higher than those measured in the evening; the differences were 5.7/5.0 mmHg in women (ranges across the cohorts, 5.3-6.8/4.7-5.4 mmHg) and 7.3/7.7 mmHg in men (ranges, 6.4-8.5/7.0-8.7 mmHg). In contrast, the home pulse rate in women and men was 2.4 (range, 1.5-3.7) and 5.6 (range, 4.6-6.6) beats per minute, respectively, higher in the evening than in the morning. We demonstrated the current status of home BP and home pulse rate in relation to sex, age, and antihypertensive treatment status in the Japanese general population. The approach by which fine-clustered aggregate statistics were collected and integrated could address practical issues raised in epidemiological research settings.

DOI： 10.1038/s41440-020-0530-1

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Other Link： http://www.nature.com/articles/s41440-020-0530-1

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is a common subclinical feature of the aging brain. Steps per day may contribute to its prevention. We herein investigated the association between step counts and CSVD in a healthy Japanese male population. METHODS: We analyzed data from 680 men who were free of stroke and participated in this observational study. Seven-day step counts were assessed at baseline (2006-2008) using a pedometer. CSVD was assessed at follow-ups (2012-2015) based on deep and subcortical white matter hyperintensities (WMHs), periventricular hyperintensities, lacunar infarcts, and cerebral microbleeds on magnetic resonance imaging. Using a logistic regression analysis, we computed the adjusted odds ratios, with 95% CIs, of prevalent CSVD according to quartiles of step counts (reference: Q1). We also investigated the association between step counts and WMH volumes using a quantile regression. RESULTS: Steps per day were significantly associated with lower odds ratios, with the lowest at Q3 (8175-10 614 steps/day), of higher (versus low or no burden) deep and subcortical WMHs (odds ratio, 0.52 [95% CI, 0.30-0.89]), periventricular hyperintensities (0.50 [95% CI, 0.29-0.86]), and lacunar infarcts (0.52 [95% CI, 0.30-0.91]) compared with Q1 (≤6060 steps/day) but not cerebral microbleeds. An inverse linear association was observed between step counts and WMH volumes. These associations were independent of age and smoking and drinking status and remained consistent when adjusted for vascular risk factors. CONCLUSIONS: We found a J-shaped relationship between step counts and prevalent CSVD in healthy Japanese men, with the lowest risk being observed among participants with ≈8000 to 10 000 steps/day. Higher steps were also associated with lower WMH volumes.

DOI： 10.1161/STROKEAHA.120.030141

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

BACKGROUND AND AIMS: Dysfunctional high-density lipoprotein (HDL) is a risk factor for cardiovascular disease (CVD) beyond HDL concentrations. Recently, a novel method has been introduced to measure LOX-1 ligand containing apolipoprotein AI (LAA), which is an indicator of various types of modified HDL with binding capacity to LOX-1 and related to impaired anti-atherogenic functions of HDL. This study aimed to examine the relationship between LAA as a novel marker of dysfunctional HDL and coronary artery calcification (CAC). METHODS: We selected 910 community-dwelling Japanese men aged 40-79 years without a history of CVD. The odds ratios per 1SD of LAA for the presence of CAC (Agatston score >10) were estimated using logistic regression model adjusted for confounders, including HDL-C or HDL particle (HDL-P) concentration. In addition, we performed further analysis stratified by age (<65 and ≥ 65 years). RESULTS: The mean age of the participants was 63.6 years, and the median LAA was 187.0 ng/mL. The prevalent CAC was 46.2%. The multivariable adjusted odds ratio (95% confidence interval) per 1SD of LAA for CAC was 1.14 (0.96-1.36) for all participants. After stratification by age, multivariable adjusted odds ratios per 1SD of LAA were 1.34 (1.02-1.76) and 0.97 (0.77-1.23) in men aged <65 and ≥ 65 years, respectively. CONCLUSIONS: The present study showed that LAA was associated with CAC independent of HDL-C or HDL-P in middle-aged Japanese men. This finding suggests that LAA might be an early marker for CVD events. Future longitudinal studies are warranted.

DOI： 10.1016/j.atherosclerosis.2020.09.013

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Evidence regarding the effect of psychological factors and evacuation on cardiovascular disease occurrence after large-scale disasters is limited. This prospective study followed up a total of 37,810 Japanese men and women aged 30–89 years from the Fukushima Prefecture with no history of stroke or heart disease at baseline (2012), until 2017. This period included 3000 cardiovascular events recorded through questionnaires and death certificates. The participants’ psychological distress, trauma reaction, and evacuation status were defined, and divided into four groups based on combinations of psychological factors and evacuation status. We calculated the hazard ratios and 95% confidence intervals for only psychological, only evacuation, or both of them compared with neither using Cox proportional hazard models. Psychological factors along with evacuation resulted in approximately 5% to 25% higher magnitude of stroke and heart disease risk than psychological factors only among men. Compared to neither, the multivariable hazard ratios of those with both psychological distress and evacuation were 1.75 for stroke and 1.49 for heart disease, and those of both trauma reaction and evacuation were 2.01 and 1.57, respectively, among men. Evacuation combined with psychological factors increased the risk of stroke and heart disease risks especially in men after the Great East Japan Earthquake.

DOI： 10.3390/ijerph17217832

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Language：English   Publisher：Japan Atherosclerosis Society  

AIM: Coronary artery calcification (CAC) is an independent predictor of stroke and dementia, in which subclinical cerebrovascular diseases (SCVDs) play a vital pathogenetic role. However, few studies have described the association between CAC and SCVDs. Therefore, the aim of this study was to assess the clinical relationship between CAC and SCVDs in a healthy Japanese male population. METHODS: In this observational study, 709 men, free of stroke, were sampled from a city in Japan from 2010 to 2014. CAC was scored using the Agatston method. The following SCVDs were assessed using magnetic resonance imaging: intracranial arterial stenosis (ICAS), lacunar infarction, deep and subcortical white matter hyperintensity (DSWMH), periventricular hyperintensity (PVH), and microbleeds. The participants were categorized according to CAC scores as follows: no CAC (0), mild CAC (1-100), and moderate-to-severe CAC (＞100). The adjusted odds ratios of prevalent SCVDs were computed in reference to the no-CAC group using logistic regression. RESULTS: The mean (standard deviation) age of the participants was 68 (8.4) years. Participants in the moderate-to-severe CAC category showed significantly higher odds of prevalent lacunar infarction, DSWMH, and ICAS in age-adjusted and risk-factor-adjusted models. Microbleeds and PVH, in contrast, did not show any significant associations. The trends for CAC with lacunar infarction, DSWMH, and ICAS were also significant (all P-values for trend ≤ 0.02). CONCLUSIONS: Higher CAC scores were associated with higher odds of lacunar infarction, DSWMH, and ICAS. The presence and degree of CAC may be a useful indicator for SCVDs involving small and large vessels.

DOI： 10.5551/jat.51284

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

Background Myotonic dystrophy type 1 involves cardiac conduction disorders. Cardiac conduction disease can cause fatal arrhythmias or sudden death in patients with myotonic dystrophy type 1. Methods and Results This study enrolled 506 patients with myotonic dystrophy type 1 (aged ≥15 years; >50 cytosine-thymine-guanine repeats) and was treated in 9 Japanese hospitals for neuromuscular diseases from January 2006 to August 2016. We investigated genetic and clinical backgrounds including health care, activities of daily living, dietary intake, cardiac involvement, and respiratory involvement during follow-up. The cause of death or the occurrence of composite cardiac events (ie, ventricular arrhythmias, advanced atrioventricular blocks, and device implantations) were evaluated as significant outcomes. During a median follow-up period of 87 months (Q1-Q3, 37-138 months), 71 patients expired. In the univariate analysis, pacemaker implantations (hazard ratio [HR], 4.35; 95% CI, 1.22-15.50) were associated with sudden death. In contrast, PQ interval ≥240 ms, QRS duration ≥120 ms, nutrition, or respiratory failure were not associated with the incidence of sudden death. The multivariable analysis revealed that a PQ interval ≥240 ms (HR, 2.79; 95% CI, 1.9-7.19, P<0.05) or QRS duration ≥120 ms (HR, 9.41; 95% CI, 2.62-33.77, P < 0.01) were independent factors associated with a higher occurrence of cardiac events than those observed with a PQ interval <240 ms or QRS duration <120 ms; these cardiac conduction parameters were not related to sudden death. Conclusions Cardiac conduction disorders are independent markers associated with cardiac events. Further investigation on the prediction of occurrence of sudden death is warranted.

DOI： 10.1161/JAHA.119.015709

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

Background and aims: To examinewhether smoking habits, including smoking amount and cessation duration at baseline, are associated with atherosclerosis progression.Methods: At baseline (2006-08, Japan), we obtained smoking status, amount of smoking and timesince cessation for quitters in a community-based randomsample of Japanesemen initially aged 40-79 years and free of cardiovascular disease. Coronary artery calcification (CAC) and aortic artery calcification (AAC) as biomarker of atherosclerosis was quantified using Agatston's method at baseline and after 5 years of follow-up. We defined progression of CAC and AAC (yes/no) using modified criteria by Berry.Results: A total of 781 participants was analyzed. Multivariable adjusted odds ratios (ORs) of CAC and AAC progression for current smokers were 1.73 (95% CI, 1.09-2.73) and 2.47 (1.38-4.44), respectively, as compared to never smokers. In dose-response analyses, we observed a graded positive relationship of smoking amount and CAC progression in current smokers (multivariable adjusted ORs: 1.23, 1.72, and 2.42 from the lowest to the highest tertile of pack-years). Among the former smokers, earlier quitters (>= 10.7 years) had similar ORs of the progression of CAC and AAC to that of participants who had never smoked.Conclusions: Comparedwith never smokers, current smokers especially thosewith greater pack-years at baseline had higher risk of atherosclerosis progression in community-dwelling Japanese men. Importantly, the residual adverse effect appears to be present for at least ten years after smoking cessation. The findings highlight the importance of early avoidance or minimizing smoking exposure for the prevention of atherosclerotic disease. (c) 2020 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.ijcard.2020.05.016

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本循環器学会  

AIM: The relationship of blood pressure (BP) indexes (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse pressure [PP], mean arterial pressure [MAP]) to subclinical cerebrovascular diseases (SCVDs) remains unclear. This study aimed to elucidate the relationship of four BP indexes measured at two visits on SCVDs assessed by magnetic resonance imaging (MRI) in general Japanese men. METHODS: In general Japanese men aged 40-79 years (N=616), office BP indexes were measured at two visits (Visits 1 [2006-2008] and 2 [2010-2014]). MRI images obtained on the third visit (2012-2015) were examined for prevalent SCVDs: lacunar infarction, periventricular hyperintensity (PVH), deep subcortical white matter hyperintensity (DSWMH), microbleeds, and intracranial artery stenosis (ICAS). Using a multivariable logistic regression analysis, we computed and estimated the odds ratio of each prevalent SCVD for one standard deviation higher BP indexes. The same analyses were performed using home BP. RESULTS: All four office BP indexes at both visits associated with lacunar infarction. Visit 1 and 2 DBP and Visit 1 MAP associated with PVH and DSWMH, and Visit 1 SBP associated with DSWMH. All Visit 2 BP indexes appear to show stronger association with microbleeds than Visit 1 indexes, and Visit 1 and 2 SBP, PP, and MAP showed similar associations with ICAS. Additional analyses using home BP indexes revealed similar relationships; however, the significance of some relationships decreased. CONCLUSION: In general Japanese men, BP indexes were associated with most of SCVDs, and BP indexes measured at different periods associated with different SCVDs assessed by MRI.

DOI： 10.5551/jat.58537

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Epidemiological Association  

BACKGROUND: The association of proteinuria and reduced estimated glomerular filtration rate (eGFR) with cognition needs more clarification. We cross-sectionally examined whether proteinuria and reduced eGFR, even in moderate stages, were independently associated with lower cognition in a community-based sample of elderly men. METHODS: Our cohort initially comprised 1,094 men aged 40-79 years from a random sample from Shiga, Japan in 2006-2008. Of 853 men who returned for the follow-up examination (2009-2014), we analyzed 561 who were ≥65 years, free of stroke, and completed the Cognitive Abilities Screening Instrument (CASI) at follow-up (higher CASI scores [range 0 to 100] indicate better cognition). Proteinuria was assessed via dipstick. eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration Equation. Participants were divided into three groups either by eGFR (≥60, 59-40, and <40 mL/min/1.73 m2) or by proteinuria (no, trace, and positive), considered normal, moderate, and advanced, respectively. Using linear regression, we computed mean CASI score, with simultaneous adjustment for proteinuria and eGFR in addition to other potential confounders. RESULTS: Significant trends of lower cognition were observed across the groups of worse proteinuria and lower eGFR independently: multivariable-adjusted mean CASI scores were 90.1, 89.3, and 88.4 for proteinuria (Ptrend = 0.029), and 90.0, 88.5, and 88.5 for eGFR (Ptrend = 0.015) in mutual-adjustment model. CONCLUSIONS: Proteinuria and reduced eGFR, even in their moderate stages, were independently associated with lower cognition in a community-based sample of elderly men. The results suggest the importance of proteinuria and low eGFR for early detection and prevention of cognitive decline.

DOI： 10.2188/jea.JE20180258

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BACKGROUND: Cognitive dysfunction has been recognized as a diabetes-related complication. Whether hyperglycemia or elevated fasting glucose are associated with cognitive decline remains controversial. We aimed to investigate the relationship between fasting glucose levels and cognitive function in diabetic and non-diabetic individuals. METHODS: Participants were Japanese diabetic (n = 191) and non-diabetic (n = 616) men, aged 46-81 years, from 2010-2014. Blood samples were taken after a 12 h fast. The Cognitive Ability Screening Instrument (CASI), with a maximum score of 100, was used for cognitive assessment. Cognitive domains of CASI were also investigated. Fractional logit regression with covariate adjustment for potential confounders was used to model cross-sectional relationships between fasting blood glucose and CASI score. RESULTS: For diabetic individuals, CASI score was 0.38 (95% confidence interval: 0.66-0.12) lower per 1 mmol/L higher fasting glucose level. Short-term memory domain also exhibited an inverse association. For non-diabetic individuals, a reverse U-shaped relationship was observed between fasting glucose and cognitive function, identifying a threshold for highest cognitive performance of 91.8 CASI score at 3.97-6.20 mmol/L (71.5-111.6 mg/dL) fasting glucose. Language ability domain displayed a similar relationship with fasting glucose. CONCLUSIONS: Elevated fasting glucose levels in diabetic men were associated with lower cognitive function, in which short-term memory was the main associated domain. Interestingly, in non-diabetic men, we identified a threshold for the inverse relationship of elevated fasting glucose with cognitive function. Contrastingly to diabetic men, language ability was the main associated cognitive domain among non-diabetic men.

DOI： 10.2188/jea.JE20180193

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

Background: Metabolic syndrome (MetS) is a global health problem. Physical activity (PA) is a known modifiable risk factor for MetS and individual MetS components. However, the role of PA could differ between sub-populations due to differences in the variability of PA and other MetS risk factors. To examine these differences, multi-country studies with standardized outcome measurement methods across cohorts are needed. Methods: Cross-sectional PA levels (total and domain specific) in healthy middle-aged (44-56 years) men in the Risk Factor Assessment among Japanese and U.S. Men in the Post-World War II Birth Cohort (ERA-JUMP) Study (n = 730; American: n = 417; Japanese: n = 313; from population-representative samples in Pittsburgh, Pennsylvania, USA, and Kusatsu, Shiga, Japan) were compared. The relationships between PA levels and MetS (overall and specific components) in/across the American and Japanese sub-cohorts (adjusting for age, smoking, and alcohol consumption) were also assessed using the same instruments (pedometer and validated questionnaire) to measure PA in both cohorts. Results: A total of 510 individuals provided complete data on PA (American: n = 265; Japanese: n = 245). The American cohort had significantly lower mean ± SD steps/day (7878 ± 3399 steps/day) vs. the Japanese cohort (9055 ± 3797 steps/day) (p < 0.001) but had significantly higher self-reported moderate-vigorous leisure PA (American: 15.9 (7.4-30.3) metabolic task equivalent hours per week (MET-h/week) vs. Japanese: 4.0 (0-11.3) MET-h/week, p < 0.0001). In both sub-cohorts, each 1000 steps/day increase was associated with lower odds of having MetS (American: OR = 0.90, 95%CI: 0.83-0.98; Japanese: OR = 0.87, 95%CI: 0.79-0.95) and the individual MetS component of high waist circumference (American: OR = 0.86, 95%CI: 0.79-0.94; Japanese: OR = 0.87, 95%CI: 0.80-0.95). In the American cohort only, higher self-reported leisure PA (Met-h/week) was associated with lower odds of MetS and high waist circumference (OR = 0.98, 95%CI: 0.97-0.99 for MetS and waist circumference, respectively). Conclusion: Higher total step counts/day had an important protective effect on MetS prevalence in both the Japanese and American cohorts, despite differences in PA levels and other MetS risk factors. The effect of steps/day (across all intensity levels) was much greater than domain-specific moderate-vigorous PA captured by questionnaire, suggesting the need for measurement tools that can best capture total movement when examining the effects of PA on MetS development.

DOI： 10.1016/j.jshs.2019.09.007

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.diabres.2020.108002

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Other Link： https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18H04074/

Language：English   Publishing type：Research paper (scientific journal)  

AIM: Computed tomography (CT) can directly provide information on body compositions and distributions, compared to anthropometric indices. It has been shown that various obesity indices are associated with carotid intima-media thickness (IMT). However, whether CT-based obesity indices are stronger than anthropometric indices in association with atherosclerosis remains to be determined in a general population. METHODS: We cross-sectionally assessed carotid IMT using ultrasound in 944 community-dwelling Japanese men free of stroke and myocardial infarction. CT image at the L4-L5 level was obtained to compute areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Anthropometric measures assessed included body mass index (BMI), waist circumference, and waist-to-hip ratio. Using multivariable linear regression, slopes of IMT per 20th to 80th percentile of each index were compared. We also compared the slope of index with simultaneous adjustment for BMI in the same model. RESULTS: Areas of VAT and SAT were positively associated with IMT, but not stronger than those of anthropometric indices in point estimates. Among all obesity indices, BMI was strongest in association with IMT after adjusting for age and lifestyle factors or further adjusting for metabolic factors. In simultaneous adjustment models, BMI, but not CT-based indices, remained significant and showed the strongest association. CONCLUSIONS: In community-dwelling Japanese men, anthropometric obesity indices, BMI in particular, were more strongly associated with carotid atherosclerosis than CT-based obesity indices. The association of general obesity with carotid atherosclerosis was strong and adding CT-based obesity measure did not considerably influence in the association.

DOI： 10.5551/jat.47977

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMJ  

<sec><title>Objective</title>This cross-sectional study examined whether contrasting distributions of nuclear magnetic resonance (NMR)-measured lipoproteins contribute to differences in the prevalence of subclinical atherosclerosis measured using coronary artery calcium (CAC) between the two groups of middle-aged males: the US-residing Caucasian (US-White) and Japan-residing Japanese (Japanese).

</sec><sec><title>Methods</title>In a population-based study of 570 randomly selected asymptomatic men aged 40–49 years (270 US-White and 300 Japanese), we examined the relationship between race/ethnicity, NMR-measured lipoproteins and CAC (measured by Electron Beam CT and quantified using the Agatston method) using multivariable robust Poisson regression adjusting for traditional and novel risk factors for coronary heart disease (CHD).

</sec><sec><title>Results</title>The US-White compared with the Japanese had significantly different NMR-measured lipoprotein particle distributions. The US-White had a significantly higher prevalence of CAC≥10 (CAC-prevalence) compared with the Japanese adjusting for CHD risk factors (prevalence ratio (PR)=2.10; 95% CI=1.24 to 3.48), and this difference was partially attenuated (~18%) with further adjustment for lipoprotein levels (PR=1.73; 95% CI=1.02 to 3.08). There was no reclassification improvement with further addition of lipoproteins particle concentrations/size to a model that already included traditionally measured lipids (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), cardiovascular risk factors, and inflammatory markers (net reclassification improvement index=−2% to 3%).

</sec><sec><title>Conclusions</title>Variations in the distribution of NMR-measured lipoprotein particles partially accounted for the difference in the CAC-prevalence between middle-aged US-White and Japanese men.

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DOI： 10.1136/openhrt-2019-001119

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OBJECTIVE: We conducted a cross-sectional study to clarify whether home blood pressure (HBP) is more strongly associated with coronary artery calcification (CAC) than accurately measured office blood pressure (OBP) among the general population of Japanese men. METHODS: We analyzed the data of 919 Japanese male participants who were randomly selected from general population (mean age 64.5 years). OBP was measured twice consecutively by a trained nurse using electrical device after 5 min of complete rest alone in a sitting position in a silent room. The participants were asked to measure HBP with an electrical device once in the morning during 7 consecutive days. CAC was assessed using computed tomography. Presence of CAC was defined as Agatston score at least 10. We calculated odds ratios for the presence of CAC per one SD higher OBP and HBP adjusted for age and other cardiovascular risk factors. RESULTS: The mean systolic OBP (SD) and HBP (SD) were 136.8 (19.0) and 137.2 (18.5) mmHg, respectively, without statistical difference between the two (P = 0.595). OBP and HBP were highly correlated (r = 0.74 P < 0.001). CAC was found in 454 (49.4%) participants. Multivariable-adjusted odds ratios [95% confidence interval (CI)] for the presence of CAC were comparable between OBP (1.32, 95% CI: 1.12-1.56) and HBP (1.35, 95% CI: 1.14-1.60) (P heterogeneity = 0.813). CONCLUSION: The strength of association of accurately measured OBP with CAC was comparable with that of HBP among randomly selected male general population aged 40-79 years.

DOI： 10.1097/HJH.0000000000002080

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DOI： 10.5551/jat.ER17244

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Other Link： http://orcid.org/0000-0002-3283-8196

Language：English  

BACKGROUND: Excessive alcohol intake has been shown to be associated with cardiovascular disease via metabolic pathways. However, the relationship between alcohol intake and obesity has not been fully elucidated. We aimed to examine the association of alcohol consumption with fat deposition and anthropometric measures. METHODS: From 2006-2008, we conducted a cross-sectional study in a population-based sample of Japanese men aged 40 through 79 years. Areas of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated using computed tomography imaging. Based on a questionnaire, we classified participants into five groups according to weekly alcohol consumption, excluding former drinkers: non-drinkers (0 g/week), 0.1-160.9, 161-321.9, 322-482.9, and ≥483 g/week. Multivariable linear regression was used to estimate adjusted means of obesity indices for each group. RESULTS: We analyzed 998 men (mean age and body mass index [BMI], 63.8 years and 23.6 kg/m2, respectively). Higher weekly alcohol consumption was strongly and significantly associated with higher abdominal VAT area, percentage of VAT, and VAT-to-SAT ratio (all P for trend <0.001), and also with waist circumferences and waist-to-hip ratio (P for trend = 0.042 and 0.007, respectively). These associations remained significant after further adjustment for BMI, whereas alcohol consumption had no significant association with abdominal SAT area. CONCLUSIONS: Higher alcohol consumption was associated with higher VAT area, VAT%, and VAT-to-SAT ratio, independent of confounders, including BMI, in general Japanese men. These results suggest that alcohol consumption may have a potential adverse effect on visceral fat deposition.

DOI： 10.2188/jea.JE20170191

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Atherosclerosis Society  

AIMS: Calcification in the coronary and aortic arteries has been linked to cardiovascular morbidity and mortality. The pathophysiological influence of aortic artery calcification (AAC) differs from that of coronary artery calcification (CAC). We aimed to compare the relationships between CAC and AAC and cardiovascular disease (CVD) risk factors. METHODS: We examined a random sample of 1035 Japanese men aged 40-79 years. CAC and AAC were measured by computed tomography and scored according to the Agatston method. Using a logistic regression, we calculated the odds ratio (OR) as being in the highest quintile (Q5) of the calcification score compared to the lower quintiles (Q1-Q4) per 1 standard deviation higher CVD risk factor. Models were simultaneously adjusted for age, body mass index (BMI), systolic blood pressure, smoking (pack-year), alcohol intake, hemoglobin A1c, uric acid, estimated glomerular filtration rate (eGFR), serum lipids, and C-reactive protein. Differences in ORs were investigated using a generalized estimating equation. We performed a multiple linear regression using log-transformed CAC and AAC values as dependent variables. RESULTS: CAC and AAC were independently associated with age (OR, 95% CI: 2.30 [1.77-2.98] for CAC and 3.48 [2.57-4.73] for AAC), p for difference ＜0.001), systolic blood pressure (1.29 [1.08-1.53] and 1.28 [1.07-1.54], p for difference=0.270), and smoking (1.22, [1.04-1.43] and 1.34 [1.13-1.58]) p for difference=0.071). Alcohol correlated with AAC only (1.17 [0.97-1.41] for CAC and 1.42 [1.16-1.73] for AAC, p for difference= 0.020). CONCLUSIONS: CAC and AAC were associated with similar CVD risk factors. The strength of association slightly differed between CAC and AAC.

DOI： 10.5551/jat.44784

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Circulation Society  

BACKGROUND: Pericardial fat volume (PFV), defined as the volume of ectopic fat in and around the heart, is associated with the atherosclerotic process in coronary arteries. The magnitude of change in PFV over time and the factors affecting this change in a general population, however, have not been investigated. Methods and Results: Cardiac computed tomography (CT) was carried out at baseline and at follow-up in 623 Japanese men aged 40-79 years without a history of cardiovascular disease who were selected randomly in Kusatsu (Shiga, Japan). PFV was measured on cardiac CT in a qualified laboratory. Age, heart rate, triglycerides, and obesity measurements (weight, body mass index, and waist circumference) were significantly and positively associated with PFV at baseline. Over an average interval of 4.7 years, median PFV increased significantly from 64.1 cm3 (IQR, 47.2-90.0 cm3) to 73.6 cm3 (IQR, 53.3-98.1 cm3; P<0.001). Current smoking and heart rate were significantly and independently associated with changes in PFV (B=3.336, P<0.001 and B=6.409, P=0.003, respectively). CONCLUSIONS: PFV increased significantly over time in a population-based observational study of Japanese men. PFV change was significantly and independently associated with smoking status and heart rate, suggesting that quitting smoking might help reduce PFV, which could be expected to decrease the risk of coronary artery disease.

DOI： 10.1253/circj.cj-18-0153

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ireland Ltd  

Background: Carotid plaque has emerged as a marker of coronary heart disease (CHD) risk. Comparison of carotid plaque burden between different race/ethnic groups may provide a relative estimate of their future CHD risk. Methods: We conducted a population-based study among apparently healthy middle-aged men aged 40–49 years (ERA JUMP study (n = 924)) and recruited 310 Whites in Pittsburgh, US, 313 Japanese in Otsu, Japan, and 301 Koreans in Ansan, South Korea. The number of carotid plaque and CHD risk factors was assessed using a standardized protocol across all centers. The burden of carotid plaque was compared between race/ethnic groups after adjustment for age and BMI, and after multivariable adjustment for other CHD risk factors using marginalized zero-inflated Poisson regression models. Cross-sectional associations of risk factors with plaque were examined. Results: Whites (22.8%) had more than four-fold higher prevalence (p &lt
0.01) of carotid plaque than Japanese men (4.8%) while the prevalence among Koreans was 10.6%. These differences remained significant after adjustment for age, BMI as well as other risk factors – incidence density ratio (95% confidence interval) for plaque was 0.13 (0.07, 0.24) for Japanese and 0.32 (0.18, 0.58) for Koreans as compared to Whites. Age, hypertension and diabetes were the only risk factors significantly associated with presence of carotid plaque in the overall population. Conclusion: Whites have significantly higher carotid plaque burden than men in Japan and Korea. Lower carotid plaque burden among Japanese and Koreans is independent of traditional CVD risk factors.

DOI： 10.1016/j.ijcard.2018.03.010

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DOI： 10.1016/j.atherosclerosis.2018.07.039

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

BACKGROUND/OBJECTIVES:Clinical trials of eicosapentaenoic acid (EPA) among high-risk groups in Japan in which consumption of mairne-omega-3 fatty acids (OM3) is much higher than other countries showed slower progression of coronary atherosclerosis. We aimed to determine the cross-sectional associations of coronary artery calcification (CAC) and calcium density with OM3, EPA, and docosahexaenoic acid (DHA), two principal OM3, in the general population in Japan. SUBJECTS/METHODS:The Shiga Epidemiological Study of Subclinical Atherosclerosis examined a population-based sample of 1074 men aged 40-79 in 2006-08 for computed tomography-measured CAC score (CCS), a well-established biomarker of coronary atherosclerosis, CAC density score (CDS), a potential marker of plaque stabilization, serum levels of OM3, and risk factors. RESULTS:Prevalence of CCS > 0, ≥ 100, and ≥ 300 was 65.8%, 25.9%, and 12.9%, respectively; the mean (SD) OM3, EPA, and DHA were 10.1% (3.2), 3.2% (1.7), and 5.9% (1.6), respectively. Odds ratios (95% CI, p-value) of CCS 0, 100, and 300 in ordinal logistic regression associated with 1 SD increase of OM3, EPA, and DHA were 0.91 (0.81-1.03, p = 0.12), 0.99 (0.88-1.11, p = 0.87) and 0.84 (0.74-0.94, p = < 0.01), respectively. The inverse association of DHA with CCS remained significant in multivariate-adjusted model: odds ratio of 0.87 (0.77-0.99, p = 0.03). Blood levels of OM3, EPA, or DHA did not have any significant associations with CDS. CONCLUSIONS:DHA but not EPA had a significant inverse association with coronary atherosclerosis in the general population with high levels of OM3. Future trials are warranted comparing the effect of high-dose DHA and EPA on atherosclerosis and cardiovascular outcomes.

DOI： 10.1038/s41430-018-0242-7

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Other Link： http://www.nature.com/articles/s41430-018-0242-7

Language：English   Publishing type：Research paper (scientific journal)  

AIM: The clinical significance of coronary artery calcification (CAC) is not fully determined in general East Asian populations where background coronary heart disease (CHD) is less common than in USA/Western countries. We cross-sectionally assessed the association between CAC and estimated CHD risk as well as each major risk factor in general Japanese men. METHODS: Participants were 996 randomly selected Japanese men aged 40-79 y, free of stroke, myocardial infarction, or revascularization. We examined an independent relationship between each risk factor used in prediction models and CAC score ≥100 by logistic regression. We then divided the participants into quintiles of estimated CHD risk per prediction model to calculate odds ratio of having CAC score ≥100. Receiver operating characteristic curve and c-index were used to examine discriminative ability of prevalent CAC for each prediction model. RESULTS: Age, smoking status, and systolic blood pressure were significantly associated with CAC score ≥100 in the multivariable analysis. The odds of having CAC score ≥100 were higher for those in higher quintiles in all prediction models (p-values for trend across quintiles ＜0.0001 for all models). All prediction models showed fair and similar discriminative abilities to detect CAC score ≥100, with similar c-statistics (around 0.70). CONCLUSIONS: In a community-based sample of Japanese men free of CHD and stroke, CAC score ≥100 was significantly associated with higher estimated CHD risk by prediction models. This finding supports the potential utility of CAC as a biomarker for CHD in a general Japanese male population.

DOI： 10.5551/jat.42416

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BACKGROUND:Abdominal fat distribution varies across groups with different races or environments. Whether environmental factors, apart from racial differences, affect abdominal fat distribution is unknown. METHODS:We compared the abdominal fat distribution of four groups; different races with similar environments (Caucasians vs. Japanese Americans), different environments with an identical race (Japanese Americans vs. Japanese), and similar races with similar environments (Japanese vs. Koreans). A population-based sample of 1212 men aged 40-49 were analyzed: 307 Caucasians and 300 Japanese Americans in the United States, 310 Japanese in Japan, and 295 Koreans in Korea. We compared the proportion of visceral adipose tissue area to total abdominal adipose tissue area (VAT%) and other factors that can affect abdominal fat distribution (smoking, alcohol use, physical activity levels, and metabolic factors). RESULTS:VAT% was significantly higher in Japanese and Koreans than in Japanese Americans and Caucasians (50.0, 48.5, 43.2, 41.0%, respectively, P < 0.001). Even after adjustment for possible confounders, the significant VAT% difference remained in comparing groups with identical race but different environments (i.e., Japanese vs. Japanese Americans). In contrast, comparing groups with different races but similar environments (i.e., Caucasians vs. Japanese Americans), VAT% was not significantly different. Comparing groups with similar races and similar environments (i.e., Japanese vs. Koreans), VAT% did not significantly differ. CONCLUSIONS:Environmental differences, apart from racial differences, affect the difference in abdominal fat distribution across different groups in middle-aged men.

DOI： 10.1089/met.2017.0132

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Language：English   Publishing type：Research paper (scientific journal)  

Data presented in this article are supplementary data to our primary article 'Association of Alcohol Consumption and Aortic Calcification in Healthy Men Aged 40-49 Years for the ERA JUMP Study' [1]. In this article, we have presented supplementary tables showing the independent association of alcohol consumption with coronary artery calcification using Tobit conditional regression and ordinal logistic regression.

DOI： 10.1016/j.dib.2018.02.032

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Atherosclerosis Society  

AIM:We aimed to investigate the association between reduced lung function and cerebral small vessel diseases via cranial magnetic resonance imaging (MRI) in the cross-sectional study of the general Japanese population. METHODS:We recruited participants aged ≥40 years from the general population of a single city in Japan. We clarified the comorbidities and treatments, smoking habits, second-hand smoke exposure, current alcohol consumption, education level, exercise habits, and occupation. The pulmonary function test was performed to assess the forced expiratory volume in 1 second (FEV1) % predicted and forced vital capacity (FVC) % predicted values. Cranial MRI was performed to evaluate the white matter lesions (WMLs) and lacunar infarcts. We examined the association of the WMLs and lacunar infarcts with a 1-standard deviation (SD) lower in the FEV1 % predicted and FVC % predicted, on the basis of the smoking status. RESULTS:A total of 473 men were examined. The association of WMLs and lacunar infarcts with the spirometry-based indices were significant only in never smokers. The association between lung function impairment and cerebral small vessel disease did not change after further adjusting for second-hand smoke exposure. CONCLUSION:In a community-based sample of Japanese men, we found an association between reduced lung function and WMLs and lacunar infarcts in never smokers.

DOI： 10.5551/jat.42127

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Atherosclerosis Society  

<p>Aim: There are few data regarding associations between sleep duration and subclinical atherosclerosis in Japan. The aim of this study was to evaluate associations of self-reported sleep duration with calcification in the coronary arteries (CAC) and carotid intima media thickness (IMT) in Japanese men.</p><p>Methods: This was a cross-sectional survey of 1093 randomly selected men from Kusatsu City, Japan. Average sleep duration on weekdays was estimated through questionnaire; CAC by computed tomography; and carotid IMT by ultrasonography.</p><p>Results: The prevalence of CAC was 50.0% for participants with sleep duration ＜5.5 h, 43.9% with 5.5–6.4 h, 50.0% with 6.5–7.4 h, 49.3% with 7.5–8.4 h, and 62.5% with ≥8.5 h. In univariate analysis, participants with sleep duration ≥8.5 h had significantly higher prevalence of CAC than those with 6.5–7.4 h (p=0.043). After adjustment for age and other risk factors, however, the association was not significant (p=0.776). The average IMT was 0.85 mm for participants with sleep duration ＜5.5 h, 0.83 mm with 5.5–6.4 h, 0.85 mm with 6.5–7.4 h, 0.88 mm with 7.5–8.4 h, and 0.90 mm with ≥8.5 h. None of the differences in IMT observed in crude or multivariable-adjusted analyses was significant (all p＞0.1).</p><p>Conclusion: Self-reported sleep duration was not associated with increased CAC or carotid IMT in a general population of Japanese men.</p>

DOI： 10.5551/jat.40527

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ireland Ltd  

Background and aims Several studies have reported a significant inverse association of light to moderate alcohol consumption with coronary heart disease (CHD). However, studies assessing the relationship between alcohol consumption and atherosclerosis have reported inconsistent results. The current study was conducted to determine the relationship between alcohol consumption and aortic calcification. Methods We addressed the research question using data from the population-based ERA-JUMP Study, comprising of 1006 healthy men aged 40–49 years, without clinical cardiovascular diseases, from four race/ethnicities: 301 Whites, 103 African American, 292 Japanese American, and 310 Japanese in Japan. Aortic calcification was assessed by electron-beam computed tomography and quantified using the Agatston method. Alcohol consumption was categorized into four groups: 0 (non-drinkers), ≤1 (light drinkers), &gt
1 to ≤3 (moderate drinkers) and &gt
3 drinks per day (heavy drinkers) (1 drink = 12.5 g of ethanol). Tobit conditional regression and ordinal logistic regression were used to investigate the association of alcohol consumption with aortic calcification after adjusting for cardiovascular risk factors and potential confounders. Results The study participants consisted of 25.6% nondrinkers, 35.3% light drinkers, 23.5% moderate drinkers, and 15.6% heavy drinkers. Heavy drinkers [Tobit ratio (95% CI) = 2.34 (1.10, 4.97)
odds ratio (95% CI) = 1.67 (1.11, 2.52)] had significantly higher expected aortic calcification score compared to nondrinkers, after adjusting for socio-demographic and confounding variables. There was no significant interaction between alcohol consumption and race/ethnicity on aortic calcification. Conclusions Our findings suggest that heavy alcohol consumption may be an independent risk factor for atherosclerosis.

DOI： 10.1016/j.atherosclerosis.2017.11.017

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CAMBRIDGE UNIV PRESS  

Equol, a metabolite of the dietary isoflavone daidzein, is produced by the action of gut bacteria in some individuals who are termed as equol-producers. It is proposed to have stronger atheroprotective properties than dietary isoflavones. We examined a cross-sectional association of dietary isoflavones and equol-producer status with coronary artery calcification (CAC), a biomarker of coronary atherosclerosis, among men in Japan. A population-based sample of 272 Japanese men aged 40-49 years recruited from 2004 to 2007 was examined for serum isoflavones, serum equol, CAC and other factors. Equol-producers were classified as individuals having a serum level of equol &gt;83 nm. The presence of CAC was defined as a coronary Ca score 10 Agatston units. The associations of dietary isoflavones and equol-producers with CAC were analysed using multiple logistic regression. The median of dietary isoflavones, equol and CAC were 5127 (interquartile range (IQR) 1941, 11700), 91 (IQR 010, 331) and 00 (IQR 00, 10) nm, respectively. Prevalence of CAC and equol-producers was 96 and 160 %, respectively. Dietary isoflavones were not significantly associated with CAC. After multivariable adjustment, the OR for the presence of CAC in equol-producers compared with equol non-producers was 010 (95 % CI 001, 090, P&lt;004). Equol-producers had significantly lower CAC than equol non-producers, but there was no significant association between dietary isoflavones and CAC, suggesting that equol may be a key factor for atheroprotective properties of isoflavones in Japanese men. This finding must be confirmed in larger studies or clinical trials of equol that is now available as a dietary supplement.

DOI： 10.1017/S000711451600458X

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective: A few studies have examined the longitudinal association of blood pressure (BP) with arterial stiffness progression, and the results were inconsistent. The objective of this study was to investigate the roles of initial BP and its longitudinal change on the progression of arterial stiffness measured using brachial-ankle pulse wave velocity (baPWV).
Method: Study participants (n = 656) were from population-based samples of healthy men aged 40-49 years at baseline (213 White Americans, 47 AfricanAmericans, 152 Japanese Americans and 244 Japanese in Japan). BP measures, baPWV and other factors were examined at baseline and 4-7 years later. General linear regression was applied for statistical analyses.
Result: Annual change in SBP (standardized coefficient: 0.33, P&lt;0.001), but not its baseline level (standardized coefficient: 0.03, P = 0.495), had a positive significant association with the progression of baPWV after adjusting for a wide range of standard cardiovascular risk factors. Similarly, annual changes in DBP (standardized coefficient: 0.35, P&lt;0.001), pulse pressure (standardized coefficient: 0.15, P = 0.001) and mean arterial pressure (standardized coefficient: 0.37, P&lt;0.001) were positively associated with the progression of baPWV. None of the baseline measures were related to the progression of baPWV.
Conclusion: Our findings imply that, regardless of initial BP, effective monitoring and controlling of BP is important to slow down arterial wall stiffening and hence reduce cardiovascular risk.

DOI： 10.1097/HJH.0000000000001144

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Studies from Western countries suggest that smokers tend to display greater abdominal obesity than non-smokers, despite showing lower weight. Whether this holds true in a leaner population requires clarification. Using indices of abdominal obesity including visceral adipose tissue, we examined whether lifetime cigarette smoking is associated with unfavorable fat distribution among Japanese men. From 2006 to 2008, we conducted a cross-sectional investigation of a community-based sample of Japanese men at 40-64 years old, free of cardiovascular diseases and cancer. Areas of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated using computed tomography. We divided participants into four groups: never-smokers; and tertiles of pack-years of smoking among ever-smokers. Using multivariable linear regression, we calculated adjusted means of obesity indices (VAT, SAT, VAT-SAT ratio [VSR], and waist-hip ratio [WHR]) for each group, and mean differences between consecutive groups. We analyzed 513 men (median age, 58.2 years; current smokers, 40.1%). Two-thirds showed body mass index (BMI) < 25 kg/m(2) (median, 23.5 kg/m(2)). Overall, greater lifetime smoking group was associated with greater WHR and VSR. On average, one higher smoking group was associated with 0.005 higher WHR (95% CI, 0.001-0.008; P = 0.005) and 0.041 greater VSR (95% CI, 0.009-0.073; P = 0.012) after adjustment for potential confounders, including BMI. In this sample of relatively lean Japanese men, greater lifetime smoking was associated with a metabolically more adverse fat distribution. Although smoking is commonly associated with lower BMI, minimizing the amount of lifetime smoking should be advocated.

DOI： 10.1016/j.pmedr.2016.06.013

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Background and aims: While alcohol consumption is known to increase plasma high-density lipoprotein (HDL) cholesterol levels, its relationship with low-density lipoprotein (LDL) cholesterol levels is unclear. Aldehyde dehydrogenase 2 (ALDH2) is a rate-controlling enzyme in alcohol metabolism, but a large number of Japanese people have the inactive allele. Here, we conducted a Mendelian randomization analysis using the ALDH2 genotype to clarify a causal role of alcohol on circulating cholesterol levels and lipoprotein particle numbers.
Methods: This study was conducted in three independent general Japanese populations (men, n = 2289; women, n = 1940; mean age 63.3 +/- 11.2 years). Alcohol consumption was assessed using a questionnaire. Lipoprotein particle numbers were determined by nuclear magnetic resonance spectroscopy.
Results: Alcohol consumption increased linearly in proportion to the number of subjects carrying the enzymatically active *1 allele in men (p &lt; 0.001). The *1 allele was also positively associated with HDL cholesterol level (adjusted mean +/- standard error, *1*1: 60 +/- 0.5, *1*2: 56 +/- 0.6, *2*2: 55 +/- 1.3 mg/dl, p &lt; 0.001) and inversely associated with LDL cholesterol level (116 +/- 0.9, 124 +/- 1.1, 130 +/- 2.6 mg/dl, p &lt; 0.001). The *1 allele was also positively associated with HDL particle numbers (per-allele: 2.60 +/- 0.32 mmol/l, p &lt; 0.001) and inversely associated with LDL particle numbers (-67.8 +/- 19.6 nmol/l, p = 0.001). Additional Mendelian randomization analysis failed to clarify the involvement of cholesteryl ester transfer protein in alcohol-related changes in lipoprotein cholesterol levels. No significant association was observed in women, presumably due to their small amount of alcohol intake.
Conclusions: Alcohol consumption has a causal role in not only increasing HDL cholesterol levels but also decreasing LDL cholesterol levels and particle numbers. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.atherosclerosis.2016.08.021

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Language：English   Publisher：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.ijcard.2016.08.215

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

BACKGROUND: Low-density lipoprotein particle (LDL-P) has recently been found to be a stronger predictor of cardiovascular disease (CVD) than LDL-cholesterol (LDL-C).
OBJECTIVES: Whether LDL-P is associated with subclinical atherosclerosis, independent of LDLC, as well as other lipid measures has not been fully examined. We aimed to analyze LDL-P associations with measures of subclinical atherosclerosis.
METHODS: We examined 870 Japanese men randomly selected from Kusatsu City, Shiga, Japan, aged 40-79 years from 2006-2008, free of clinical CVD and not using lipid-lowering medication. Cross-sectional associations of lipid measures with carotid intima-media thickness (cIMT) and coronary artery calcification (CAC; &gt;0 Agatston score) were examined.
RESULTS: LDL-P was significantly positively associated with cIMT and maintained this association after adjustments for LDL-C and other lipid measures. Although these lipid measures were positively associated with cIMT, model adjustment for LDL-P removed any significant relationships. Higher LDL-P was associated with a significantly higher odds ratio of CAC and further adjustment for LDL-C did not affect this relationship. In contrast, the LDL-C association with CAC was no longer significant after adjustment for LDL-P. Other lipid measures attenuated associations of LDL-P with CAC. Likewise, associations of these measures with CAC were attenuated when model adjustments for LDL-P were made.
CONCLUSIONS: In a community-based sample of Japanese men, free of clinical CVD, LDL-P was a robust marker for subclinical atherosclerosis, independent of LDL-C and other lipid measures. Associations of LDL-C and other lipid measures with either cIMT or CAC were generally not independent of LDL-P. (C) 2016 National Lipid Association. All rights reserved.

DOI： 10.1016/j.jacl.2015.12.027

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Objective: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme predominantly bound to low-density lipoprotein (LDL). Lp-PLA2 is recognized as playing a key role in inflammatory processes and the development of atherosclerosis. This study aimed to investigate whether Lp-PLA2 is related to subclinical atherosclerosis, independently from traditional risk factors, in a general Japanese population by analyses of both the observational study and Mendelian randomization using V279F polymorphism.
Methods and results: We cross-sectionally examined community-based sample of 929 Japanese men aged 40-79 years, without statin treatment, who were randomly selected from the resident registration. Multiple regression analyses of Lp-PLA2 activity and concentration were undertaken separately for men aged 40-49 years and 50-79 years, to clarify interactions of age and Lp-PLA2. Lp-PLA2 activity for men aged 50-79 years was significantly and positively related to intima-media thickness (IMT) (P = 0.013) and plaque index (P = 0.008) independent of traditional risk factors including small LDL particles, but not to coronary artery calcification (CAC) score. Associations with Lp-PLA2 concentration were qualitatively similar to those of activity. Corresponding relationships were not observed in men aged 40e49 years. Mendelian randomization analyses based on V279F genotype did not show any significant associations with subclinical atherosclerosis, although the homozygote and heterozygote of V279F showed low LpPLA2 activity and concentration.
Conclusions: Lp-PLA2 activity in Japanese men aged 50-79 years was associated significantly and positively with IMT and plaque in the carotid artery but Mendelian randomization did not support that LpPLA2 is a causative factor for subclinical atherosclerosis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.atherosclerosis.2015.12.027

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPANESE CIRCULATION SOC  

Background: In children with long QT syndrome (LQTS), risk factors for cardiac events have been reported, but age-, gender-and genotype-related differences in prognosis remain unknown in Asian countries.
Methods and Results: The study examined clinical prognosis at age between 1 and 20 years in 496 LQTS patients who were genotyped as either of LQT1-3 (male, n=206). Heterozygous mutations were observed in 3 major responsible genes: KCNQ1 in 271, KCNH2 in 192, and SCN5A in 33 patients. LQTS-associated events were classified into 3 categories: (1) syncope (n=133); (2) repetitive torsade de pointes (TdP, n=3); and (3) cardiopulmonary arrest (CPA, n=4). The risk of cardiac events was significantly lower in LQT1 girls than boys &lt;= 12 years (HR, 0.55), whereas LQT2 female patients &gt;= 13 years had the higher risk of cardiac events than male patients (HR, 4.60). Patients in the repetitive TdP or CPA group included 1 LQT1 female patient, 1 LQT2 male patient, and 5 LQT2 female patients. All LQT2 patients in these groups had TdP repeatedly immediately after the antecedent event. In addition, all 5 female LQT2 patients in these groups had the event after or near puberty.
Conclusions: Female LQT2 children might have repeated TdP shortly after prior events, especially after puberty.

DOI： 10.1253/circj.CJ-15-0933

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

BACKGROUND: The serum level of LOX-1 ligand containing ApoB (LAB) may reflect atherogenicity better than usual lipid parameters; however, the relationship between LAB and carotid intima-media thickness (IMT) was not clear even in Asian populations.
METHODS: A total of 992 community-dwelling Japanese men, aged 40 to 79 years, were enrolled in the present study. Serum LAB levels were measured by enzyme-linked immunosorbent assays (ELISAs) with recombinant LOX-1 and monoclonal anti-apolipoprotein B antibody.
RESULTS: Serum LAB levels (median [interquartile range], mu g cs/L) were 5341 mu g cs/L (4093-7125). The mean average IMT of the common carotid artery was highest in the fourth LAB quartile (842 mu m) compared with the first quartile (797 mu m) after adjustment for age, high-density lipoprotein cholesterol, triglyceride, body mass index, hypertension, diabetes, high sensitivity C-reactive protein, smoking, and alcohol drinking. However, this statistically significant difference was lost after further adjustment for total cholesterol (TC). After stratification using the combination of median LAB and hypercholesterolemia (serum TC &gt;= 6.21 mmol/L and/or lipid-lowering medication), the adjusted mean average IMT (standard error) in the high LAB/hypercholesterolemia group was 886 mu m (12.7), 856 mu m (16.7) in the low LAB/hypercholesterolemia group, and 833 mu m (8.4) in the low LAB/normal cholesterol group (P = .004). After further adjustment for TC, mean average IMT in the high LAB group was significantly higher than that measured in the low LAB group in hypercholesterolemic participants not taking lipid-lowering medication.
CONCLUSION: Serum LAB was associated with an increased carotid IMT in Japanese men, especially those with hypercholesterolemia. (C) 2016 National Lipid Association. All rights reserved.

DOI： 10.1016/j.jacl.2015.10.010

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

BackgroundJ wave, or early repolarization has recently been associated with an increased risk of lethal arrhythmia and sudden death, both in idiopathic ventricular fibrillation and in the general population. Hypercalcemia is one of the causes of J point and ST segment elevation, but the relationship has not been well studied. The aim of this study was to examine the effects of hypercalcemia on J point elevation.
MethodsElectrocardiographic findings were compared in 89 patients with hypercalcemia and 267 age- and sex-matched healthy controls with normocalcemia. The association of J point elevation with arrhythmia events in patients with hypercalcemia was also studied.
ResultsThe PR interval and the QRS duration were longer in patients with hypercalcemia than in normocalcemic controls. Both the QT and the corrected QT intervals were shorter in patients with hypercalcemia compared with normocalcemic controls. Conduction disorders, ST-T abnormalities, and J point elevation were more common in patients with hypercalcemia than normocalcemic controls. Following the resolution of hypercalcemia, the frequency of J point elevation decreased to a level similar to that noted in controls. During hospitalization, no arrhythmia event occurred in patients with hypercalcemia.
ConclusionHypercalcemia was associated with J point elevation.

DOI： 10.1111/anec.12303

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Atherosclerosis Society  

Aim: Pulse wave velocity (PWV is a simple and valid clinical method for assessing arterial stiffness. Coronary artery calcification (CAC is an intermediate stage in the process leading to overt cardiovascular disease (CVD and an established determinant of coro nary artery disease. This study aimed to examine the association between PWV and CAC in a population-based sample of Japanese men. Methods: This is a cross-sectional study of 986 randomly selected men aged 40-79 years from Shiga, Japan. CVD-free participants were examined from 2006 to 2008. Brachial-ankle PWV (baPWV was measured using an automatic waveform analyzer. CAC was assessed using computed tomography. Agatston scores ≥ 10 were defined as the presence of CAC. Results: Prevalence of CAC progressively increased with rising levels of baPWV: 20.6%, 41.7%, 56.3%, and 66.7% across baPWV quartiles ＜1378, 1378-1563, 1564-1849, and ＞1849 cm/s (P＜ 0.001 for trend. Associations remained significant after adjusting for age and other factors, including body mass index, systolic blood pressure, pulse rate, total and high-density lipoprotein cholesterol, hemoglobin A1c, drinking, smoking and exercise status, and the use of medication to treat hypertension, dyslipidemia and diabetes (P= 0.042 for trend. The optimal cutoff level of baPWV to detect CAC was 1612 cm/s using receiver operating characteristic curve analysis. Conclusions: Arterial stiffness as defined by an elevated baPWV is associated with an increased prevalence of CAC in a general population-based setting among Japanese men.

DOI： 10.5551/jat.30247

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Background: Brachial-ankle pulse wave velocity (baPWV) is a simple and reproducible measure of arterial stiffness and is extensively used to assess cardiovascular disease (CVD) risk in eastern Asia. We examined whether baPWV is associated with coronary atherosclerosis in an international study of healthy middle-aged men.
Methods: A population-based sample of 1131men aged 40-49 years was recruited - 257 Whites and 75 Blacks in Pittsburgh, US, 228 Japanese-Americans in Honolulu, US, 292 Japanese in Otsu, Japan, and 279 Koreans in Ansan, Korea. baPWV was measured with an automated waveform analyzer (VP2000, Omron) and atherosclerosis was examined as coronary artery calcification (CAC) by computed-tomography (GE-Imatron EBT scanner). Association of the presence of CAC (defined as &gt;= 10 Agatston unit) was examined with continuous measure as well as with increasing quartiles of baPWV.
Results: As compared to the lowest quartile of baPWV, the multivariable-adjusted odds ratio (95% Confidence Interval [CI]) for the presence of CAC in the combined sample was 1.70 (0.98, 2.94) for 2nd quartile, 1.88 (1.08, 3.28) for 3rd quartile, and 2.16 (1.19, 3.94) for 4th quartile (p-trend = 0.01). The odds for CAC increased by 19% per 100 cm/s increase (p &lt; 0.01), or by 36% per standard-deviation increase (p &lt; 0.01) in baPWV. Similar effect-sizes were observed in individual races, and were significant among Whites, Blacks and Koreans.
Conclusion: baPWV is cross-sectionally associated with CAC among healthy middle-aged men. The association was significant in Whites and Blacks in the US, and among Koreans. Longitudinal studies are needed to determine its CVD predictive ability. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ijcard.2015.04.020

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ireland Ltd  

The association of high-density lipoprotein particle (HDL-P) with atherosclerosis may be stronger than that of HDL-cholesterol (HDL-C) and independent of conventional cardiovascular risk factors. Whether associations persist in populations at low risk of coronary heart disease (CHD) remains unclear. This study examines the associations of HDL-P and HDL-C with carotid intima-media thickness (cIMT) and plaque counts among Japanese men, who characteristically have higher HDL-C levels and a lower CHD burden than those in men of Western populations. Methods: We cross-sectionally examined a community-based sample of 870 Japanese men aged 40-79 years, free of known clinical cardiovascular disease (CVD) and not on lipid-lowering medication. Participants were randomly selected among Japanese living in Kusatsu City in Shiga, Japan. Results: Both HDL-P and HDL-C were inversely and independently associated with cIMT in models adjusted for conventional CHD risk factors, including low-density lipoprotein cholesterol (LDL-C) and diabetes. HDL-P maintained an association with cIMT after further adjustment for HDL-C (P&lt
0.01), whereas the association of HDL-C with cIMT was noticeably absent after inclusion of HDL-P in the model. In plaque counts of the carotid arteries, HDL-P was significantly associated with a reduction in plaque count, whereas HDL-C was not. Conclusion: HDL-P, in comparison to HDL-C, is more strongly associated with measures of carotid atherosclerosis in a cross-sectional study of Japanese men. Findings demonstrate that, HDL-P is a strong correlate of subclinical atherosclerosis even in a population at low risk for CHD.

DOI： 10.1016/j.atherosclerosis.2015.01.031

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

BACKGROUND/OBJECTIVES: Higher volumes of ectopic cardiovascular fat (ECF) are associated with greater risk of coronary heart disease (CHD). Identifying factors that are associated with ECF volumes may lead to new preventive efforts to reduce risk of CHD. Significant racial/ethnic differences exist for overall and central adiposity measures, which are known to be associated with ECF volumes. Whether racial/ethnic differences also exist for ECF volumes and their associations with these adiposity measures remain unclear.
SUBJECTS/METHODS: Body mass index (BMI), computerized tomography-measured ECF volumes (epicardial, pericardial and their summation) and visceral adipose tissue (VAT) were examined in a community-based sample of 1199 middle-aged men (24.2% Caucasians, 7.0% African-Americans, 23.6% Japanese-Americans, 22.0% Japanese, 23.2% Koreans).
RESULTS: Significant racial/ethnic differences existed in ECF volumes and their relationships with BMI and VAT. ECF volumes were the highest among Japanese-Americans and the lowest among African-Americans. The associations of BMI and VAT with ECF differed by racial/ethnic groups. Compared with Caucasians, for each 1-unit increase in BMI, African-Americans had lower, whereas Koreans had higher increases in ECF volumes (P-values &lt; 0.05 for both). Meanwhile, compared with Caucasians, for each 1-unit increase in log-transformed VAT, African-Americans, Japanese-Americans and Japanese had similar increases, whereas Koreans had a lower increase in ECF volumes (P-value &lt; 0.05).
CONCLUSIONS: Racial/ethnic groups differed in their propensity to accumulate ECF at increasing level of overall and central adiposity. Future studies should evaluate whether reducing central adiposity or overall weight will decrease ECF volumes more in certain racial/ethnic groups. Evaluating these questions might help in designing race-specific prevention strategy of CHD risk associated with higher ECF.

DOI： 10.1038/ijo.2014.154

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

At the same level of BMI, white people have less visceral adipose tissue (VAT) and are less susceptible to developing type 2 diabetes than Japanese people. No previous population-based studies have compared insulin resistance and insulin secretion between these two races in a standardised manner that accounts for VAT. We compared HOMA-IR, HOMA of beta cell function (HOMA-beta%) and disposition index (DI) in US white men and Japanese men in Japan.
We conducted a population-based, cross-sectional study, comprising 298 white men and 294 Japanese men aged 40-49 years without diabetes. Insulin, glucose, VAT and other measurements were performed at the University of Pittsburgh. We used ANCOVA to compare geometric means of HOMA-IR, HOMA-beta% and DI, adjusting for VAT and other covariates.
White men had higher HOMA-IR, HOMA-beta% and DI than Japanese men, and the difference remained significant (p &lt; 0.01) after adjusting for VAT (geometric mean [95% CI]): 3.1 (2.9, 3.2) vs 2.5 (2.4, 2.6), 130.8 (124.6, 137.3) vs 86.7 (82.5, 91.0), and 42.4 (41.0, 44.0) vs 34.8 (33.6, 36.0), respectively. Moreover, HOMA-IR, HOMA-beta% and DI were significantly higher in white men even after further adjustment for BMI, impaired fasting glucose and other risk factors.
The higher VAT-adjusted DI in white men than Japanese men may partly explain lower susceptibility of white people than Japanese people to developing type 2 diabetes. The results, however, should be interpreted with caution because the assessment of insulin indices was made using fasting samples and adjustment was not made for baseline glucose tolerance. Further studies using formal methods to evaluate insulin indices are warranted.

DOI： 10.1007/s00125-014-3414-6

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN ATHEROSCLEROSIS SOC  

Aim: To examine whether the inflammatory markers C-reactive protein (CRP) and fibrinogen are associated with biomarkers of atherosclerosis [carotid intima-media thickness (IMT) and coronary artery calcification (CAC)] in the general male population, including Asians.
Methods: Population-based samples of 310 Japanese, 293 Japanese-American and 297 white men 40-49 years of age without clinical cardiovascular disease underwent measurement of IMT, CAC and the CRP and fibrinogen levels as well as other conventional risk factors using standardized methods. Statistical associations between the variables were evaluated using multiple linear or logistic regression models.
Results: The Japanese group had significantly lower levels of inflammatory markers and subclinical atherosclerosis than the Japanese-American and white groups (P-values all &lt; 0.001). The mean level of CRP was 0.66 vs. 1.11 and 1.47 mg/L, while that of fibrinogen was 255.0 vs. 313.0 and 291.5 mg/dl, respectively. In addition, the mean carotid IMT was 0.61 vs. 0.73 and 0.68 mm, while the mean prevalence of CAC was 11.6% vs. 32.1% and 26.3%, respectively. Body mass index (BMI) showed significant positive associations with both the CRP and fibrinogen levels. Although CRP showed a significant positive association with IMT in the Japanese men, this association became non-significant following adjustment for traditional risk factors or BMI. In all three populations, CRP was not found to be significantly associated with the prevalence of CAC. Similarly, fibrinogen did not exhibit a significant association with either IMT or the prevalence of CAC.
Conclusions: The associations between inflammatory markers and subclinical atherosclerosis may merely reflect the strong associations between BMI and the levels of inflammatory markers and incidence of subclinical atherosclerosis in both Eastern and Western populations.

DOI： 10.5551/jat.23580

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Authorship：Lead author,　Corresponding author   Language：English   Publisher：Elsevier Ireland Ltd  

DOI： 10.1016/j.ijcard.2015.02.028

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS INC  

The incidence of coronary heart disease in the United States has declined, and prevalences of several coronary disease risk factors have become comparable to those in Japan. Therefore, the burden of coronary atherosclerosis may be closer among younger persons in the 2 countries. We aimed to compare prevalences of coronary atherosclerosis, measured with coronary artery calcium scores, between men in the 2 countries by age group (45-54, 55-64, or 65-74 years). We used community-based samples of Caucasian men in the United States (2000-2002; n = 1,067) and Japanese men in Japan (2006-2008; n = 832) aged 45-74 years, stratifying them into groups with 0, 1, 2, or &gt;= 3 of the following risk factors: current smoking, overweight, diabetes, dyslipidemia, and hypertension. We calculated adjusted odds ratios of US Caucasian men's having Agatston scores of &gt;= 10, &gt;= 100, and &gt;= 400 with reference to Japanese men. Overall, the odds of Caucasian men having each Agatston cutoff point were greater. The ethnic difference, however, became smaller in younger age groups. For example, adjusted odds ratios for Caucasian men's having an Agatston score of &gt;= 100 were 2.05, 2.43, and 3.86 among those aged 45-54, 55-64, and 65-74 years, respectively. Caucasian men in the United States had a higher burden of coronary atherosclerosis than Japanese men, but the ethnic difference was smaller in younger age groups.

DOI： 10.1093/aje/kwu169

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Background: Dietary intake of long-chain n-3 PUFA (LCn3FA) among Japanese is generally higher than that in Western populations. However, little is known whether an inverse association of LCn3FA with cardiovascular disease (CVD) risk exists in a population with higher LCn3FA intake.
Objective: To investigate the association between LCn3FA intake and the long-term risk of CVDs in a Japanese general population.
Methods: We followed-up a total of 9190 individuals (56.2% women, mean age 50.0 years) randomly selected from 300 areas across Japan and free from CVDs at baseline. Dietary LCn3FA intake was estimated using household weighed food records. Cox models were used to calculate multivariate-adjusted hazard ratios (HR) and confidence intervals (CI) according to sex specific quartiles of LCn3FA intake.
Results: During 24-year follow-up (192,897 person-years), 879 cardiovascular deaths were observed. The median daily intake of LCn3FA was 0.37% kcal (0.86 g/day). Adjusted HR for CVD mortality was lower in the highest quartile of LCn3FA intake (HR 0.80; 95% CI 0.66-0.96) compared with the lowest quartile, and the trend was statistically significant (P = 0.038). The similar but statistically non-significant trends were observed for coronary heart disease death and stroke death. In analyses by age groups, the inverse associations of LCn3FA intake with the risk of total CVD death and stroke death were significant in younger individuals (30-59 years at baseline).
Conclusion: LCn3FA intake was inversely and independently associated the long-term risk of total CVD mortality in a representative sample of Japanese with high LCn3FA intake. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.atherosclerosis.2013.11.073

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AIM:To examine whether subclinical atherosclerosis of the carotid arteries is concordant with the categories in the 2012 atherosclerosis prevention guidelines proposed by the Japan Atherosclerosis Society (JAS guidelines 2012), which adopted the estimated 10-year absolute risk of coronary artery disease (CAD) death in the NIPPON DATA80 Risk Assessment Chart. METHODS:Between 2006 and 2008, 868 Japanese men 40 to 74 years of age without a history of cardiovascular disease were randomly selected from Kusatsu City, Japan. The intima media thickness (IMT) and plaque number from the common to internal carotid arteries were investigated using ultrasonography. The absolute risk of CAD death was estimated based on the individual risk factor data, and the mean IMT and plaque number in Categories Ⅰ, Ⅱ and Ⅲ of the guidelines were examined. RESULTS:The estimated 10-year absolute risk of CAD was directly related to the IMT (mean IMT (mean ± SD) (mm) for a 10-year absolute risk of ≥ 2.0% and ≥ 5.0%: 0.88 ± 0.18 and 0.95 ± 0.19, respectively) and the plaque number. These results are compatible with the categories described by the guidelines (mean IMT (mean ± SD) (mm) for Categories Ⅰ, Ⅱ, and Ⅲ: 0.70 ± 0.11, 0.81 ± 0.16 and 0.88 ± 0.18, respectively; mean plaque number: 0.9, 2.1 and 3, respectively). These findings were similar for Category Ⅲ participants with or without DM and CKD. CONCLUSIONS:Subclinical atherosclerosis of the carotid arteries is concordant with the 10-year absolute risk of CAD and the categories in the JAS guidelines 2012.

DOI： 10.5551/jat.17244

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DOI： 10.1253/circj.cj-13-0270

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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BACKGROUND:An early repolarization pattern, characterized by an elevation of the QRS-ST junction (J-point) on 12-lead electrocardiography (ECG) is associated with cardiac and sudden death. However, little is known about the prognostic significance of J-point elevation for various disease-specific cardiovascular outcomes, including coronary artery disease (CAD). METHODS AND RESULTS:To investigate the association between the presence of J-point elevation≥0.1 mV and various disease-specific cardiovascular outcomes, we conducted a 15-year prospective study in a representative general Japanese population of 7,630 individuals (41% men, mean age 52.4 years) who participated in the National Survey of Circulatory Disorders. Cox models were used to estimate the hazard ratios (HRs) adjusted for possible confounding factors. J-point elevation was present in 264 individuals (3.5%) and was associated with an increased risk of cardiac death (adjusted HR, 2.54; 95% confidence interval [CI] 1.40-4.58; P=0.002) and death from CAD (adjusted HR, 4.66; 95% CI 2.30-9.46; P<0.001). In a subgroup analysis by age, the association between J-point elevation and cardiovascular outcomes was more remarkable in middle-aged (<60 years) than in older individuals (≥60 years) (all P for interaction<0.05). CONCLUSIONS:J-point elevation on standard 12-lead ECG was an independent predictor of cardiac death and death from CAD in a representative sample of the general Japanese population, particularly among the middle-aged.

DOI： 10.1253/circj.cj-12-1273

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Authorship：Lead author,　Corresponding author  

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: In Western populations, blood pressure (BP) measured at baseline has been reported to predict long-term (over 20 years) risk of mortality from cardiovascular diseases (CVDs). However, corresponding evidence is scarce in Asia where stroke is dominant. We investigated the association between baseline BP and 24-year mortality risk due to CVD, in a representative Japanese general population. METHODS: We followed up a nationwide sample of 8592 Japanese, aged 30 years or above without a history of CVD and antihypertensive medication at baseline, for 24 years. Hazard ratios for CVD mortality in BP categories defined according to JCN7 criteria were estimated using Cox model adjusted for potential confounding factors with normal BP treated as the reference category. RESULTS: We observed 689 CVD deaths. Hazard ratios for CVD mortality were progressively and significantly increased from the category of prehypertension. Population-attributable fraction (PAF) demonstrated that 43 and 48% of CVD and stroke deaths were explained by non-normal BP at baseline. Hazard ratios and PAF were remarkably higher in younger participants (aged 30-59 years) than those in the elderly (aged 60 years or above). Particularly, in younger men, 81% of CVD deaths were explained by non-normal BP. In sensitivity analysis, participants with antihypertensive medication showed the highest hazard ratio for CVD morality compared with the other categories. CONCLUSIONS: BP levels above normal at baseline retained significant relative and absolute risks of CVD and stroke mortality during 24 years. Long-lasting burden of non-normal BP particularly in younger individuals suggests the importance of primary prevention of high BP from younger generation.

DOI： 10.1097/HJH.0b013e328359a9f7

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Language：Japanese  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2010&ichushi_jid=J02269&link_issn=&doc_id=20110113250004&doc_link_id=10.14961%2Fcra.22.389&url=https%3A%2F%2Fdoi.org%2F10.14961%2Fcra.22.389&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publisher：(株)東京医学社  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00714&link_issn=&doc_id=20230912090002&doc_link_id=10.24479%2Fkd.0000000834&url=https%3A%2F%2Fdoi.org%2F10.24479%2Fkd.0000000834&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Authorship：Lead author,　Corresponding author   Language：Japanese   Publisher：(一社)日本循環器病予防学会  

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Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publisher：(株)日本臨床社  

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Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publisher：(一社)日本循環器病予防学会  

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Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publisher：(一社)日本疫学会  

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publisher：(一社)日本アルコール・アディクション医学会  

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Language：Japanese   Publisher：日本公衆衛生学会  

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (international conference proceedings)  

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Language：Japanese   Publisher：(株)診断と治療社  

＜Headline＞1 国民の収縮期血圧平均値は、男女ともいずれの年齢階級においても過去約60年で大きく低下した一方、拡張期血圧平均値は、特に60歳未満の男性では低下傾向が明らかではない。2 高血圧有病率は依然高く、50歳以上の男性、60歳以上の女性ではおおよそ60%以上である状態が続いている。3 高血圧管理率は改善傾向にあるものの、男性では約40%、女性では約45%にとどまっており、現在のところ降圧薬内服者の半数以上は管理不十分である。4 2017年の高血圧者の推計数は計4,300万人、うち3,100万人(72%)が管理不良であった。5 日本国民の血圧水準、高血圧有病率、および高血圧管理率をさらに改善させるには、高血圧者に対するハイリスクアプローチと、国民全体でのポピュレーションアプローチを組み合わせた総合的な対策の積極的な推進が重要である。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J00697&link_issn=&doc_id=20200422190004&doc_link_id=%2Fae4digta%2F2020%2F010804%2F006%2F0445-0451%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae4digta%2F2020%2F010804%2F006%2F0445-0451%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(株)日本臨床社  

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Authorship：Lead author   Language：English   Publishing type：Article, review, commentary, editorial, etc. (international conference proceedings)  

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (international conference proceedings)  

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞はじめに 循環器疾患の古典的なリスク因子である肥満,高血圧,糖尿病,脂質異常症が合併しやすいことは以前から知られていた.現在では,腹部肥満,特に内臓脂肪型肥満(インスリン抵抗性)を基盤として,血圧上昇,血糖高値,脂質異常が集積した病態が「メタボリックシンドローム」(metabolic syndrome)と定義されている.肥満が原因となって,先述のリスク因子が軽度でも集積して存在すると循環器疾患リスクが高くなることが知られており,メタボリックシンドロームは循環器疾患の一次予防において重要な概念となっている.わが国では,欧米諸国と比較して肥満者割合が依然として低い一方で,肥満を伴わないリスク因子保有・集積者における循環器疾患リスクがメタボリックシンドローム有所見者のそれと同等か,それよりも高いことが報告されるなど,非肥満者におけるリスク因子保有・集積の重要性が認識されている.本稿は,リスク因子の集積に焦点を当て,わが国の疫学研究成果を踏まえて循環器疾患への影響を検討する.さらに,循環器疾患一次予防に関する包括的なリスク評価と,公衆衛生上の対策について概説する.

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00447&link_issn=&doc_id=20190507110008&doc_link_id=10.11477%2Fmf.1401209138&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1401209138&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Authorship：Lead author,　Last author,　Corresponding author   Language：English   Publishing type：Article, review, commentary, editorial, etc. (international conference proceedings)  

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Coronary artery calcium, quantified by computed tomography scanning, is one of the well-known measures of subclinical atherosclerosis. Coronary artery calcium is considered an end result from the long-term exposure to risk factors. CAC has been shown to improve risk stratification in asymptomatic individuals with intermediate-risk(e.g., an option to facilitate decision making)for primary prevention of atherosclerotic cardiovascular disease in the US/western countries. Coronary artery calcium also represents a surrogate of atherosclerosis burden. However, the lack of evidence regarding issues such as costs or radiation exposure related to measuring coronary artery calcium warrants further studies.

DOI： 10.20837/4201902215

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Language：Japanese   Publisher：(株)医薬ジャーナル社  

＜文献概要＞潜在性動脈硬化指標の一つとして,単純CTにより定量的に評価された冠動脈石灰化がある。一次予防において,危険因子への長期曝露の結果である冠動脈石灰化所見を用いることで,有効に動脈硬化性心血管病の発症を予測し,中等度リスク保有者の管理において治療方針の決定などリスクの層別化を行い得る可能性が検討されている。また,冠動脈石灰化は動脈硬化進展マーカーとしても用いられる。一方,冠動脈石灰化測定の費用対効果や放射線被曝の問題などでは確定的な結論が得られていない。一次予防における冠動脈石灰化の有用性の確立のために,わが国を含む冠動脈石灰化に関する研究の更なる発展およびエビデンスの集積が望まれる。

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J02593&link_issn=&doc_id=20190204290010&doc_link_id=10.20837%2F4201902215&url=https%3A%2F%2Fdoi.org%2F10.20837%2F4201902215&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：Japanese   Publisher：(NPO)日本高血圧学会  

J-GLOBAL

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publisher：(一社)日本循環器病予防学会  

日本における衛生統計・地域の疫学調査成績や国際比較を通じて、心疾患の中でも死亡率が高く疫学的知見の豊富な冠動脈疾患を中心に、その危険因子も含めて時代的な推移を概説した。心疾患全体での粗死亡率が上昇している一方、急性心筋梗塞を含む冠動脈疾患の粗死亡率は必ずしも上昇していない。また、冠動脈疾患を年齢調整死亡率で比較すると、日本は依然男女とも世界の中で最低水準と考えられた。一方で、急性心筋梗塞罹患率の都市部、男性における増加傾向が一部の疫学研究から示されており、その死亡率も近い将来上昇傾向に転じる可能性が懸念された。

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Language：English   Publisher：島根大学医学部  

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Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publisher：(公財)上原記念生命科学財団  

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Language：Japanese   Publisher：(株)メジカルビュー社  

喫煙は動脈硬化性心血管病(atherosclerotic cardiovascular disease;ASCVD)に対する最大の予防可能な危険因子である。ASCVD発症前の一般健常集団において、喫煙習慣(現在喫煙・禁煙)、特に現在喫煙は、冠動脈・頸動脈・大動脈・末梢動脈を含む全身の潜在性動脈硬化の進展と強固に関連し、これらの進展は生涯喫煙量(pack-year)の多い喫煙者・禁煙者ほど大きく、一方、早期に禁煙した禁煙者ほど生涯非喫煙者に近づくものと考えられる。欧米諸国と比較して依然喫煙率が高いわが国におけるASCVDのさらなる予防のためには、防煙ならびに喫煙者における早期の禁煙の積極的な推進が重要である。(著者抄録)

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Language：Japanese   Publisher：(株)先端医学社  

高血圧は、冠動脈疾患を含む心血管病の代表的な危険因子であり、日常診療で最もよく遭遇する疾患である。人口の急速な高齢化や生活習慣の欧米化の進展に伴い、都市部を中心とした冠動脈疾患発症率の増加および、とくに男性における高血圧有病率の上昇が今後懸念され、またアジア人では冠動脈疾患に対する高血圧の寄与度は大きいことから、わが国における冠動脈疾患予防に関して、高血圧対策が重要であると再認識する必要がある。至適血圧を超えて血圧が高くなるほど冠動脈疾患の死亡・発症リスクは高くなり、わが国における冠動脈疾患死亡の50%以上が至適血圧を超える血圧高値に起因するものと推定される。ポピュレーションアプローチを用いて国民全体の収縮期血圧平均値を4mmHg低下させることにより、冠動脈疾患死亡数が年間約5千人減少すると推計される。(著者抄録)

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Language：Japanese   Publisher：(株)南山堂  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J00821&link_issn=&doc_id=20160314060002&doc_link_id=%2Faf5thrpc%2F2016%2F009803%2F003%2F0333-0336%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faf5thrpc%2F2016%2F009803%2F003%2F0333-0336%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(株)日本医事新報社  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J03097&link_issn=&doc_id=20150312220004&doc_link_id=%2Fap4heard%2F2015%2F001904%2F005%2F0361-0369%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fap4heard%2F2015%2F001904%2F005%2F0361-0369%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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Language：Japanese   Publisher：大道学館出版部  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J01556&link_issn=&doc_id=20140124490001&doc_link_id=%2Fam3daidc%2F2014%2F009101%2F001%2F0001-0008%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fam3daidc%2F2014%2F009101%2F001%2F0001-0008%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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J-GLOBAL

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大動脈弁石灰化(AVC)と核磁気共鳴(NMR)で測定したリポ蛋白粒子との関連について、AVCと脂質の標準指標との関連と比較検討した。リポ蛋白粒子[低比重リポ蛋白(LDL)粒子(nmol/L)および高比重リポ蛋白(HDL)粒子(μmol/L)]と、LDLコレステロール(LDL-C)およびHDLコレステロール(HDL-C)(いずれもmg/dL)について検討した。2006年〜2008年に滋賀県草津市在住者から40〜79歳の日本人男性を無作為に抽出し、1094名が本研究への参加に同意した(参加率46%)。Agatstonスコア>0をAVCありと判定した。リポ蛋白粒子はNMR分光法にて測定した。脂質の第1四分位群に対する第4四分位群のAVCの多変量調整オッズ比(OR)と95%CIを求めた。874例(平均63.3±10.0歳)を解析した。AVCを認めたのは153名であった。第4四分位群のAVCの調整OR(95%CI)は、LDL粒子で2.20(1.23〜3.93)、LDL-Cで2.16(1.23〜3.78)であった。HDL粒子およびHDL-CはAVCと関連がなかった。以上から、NMRで測定したLDL粒子とAVCとの関連は、LDL-CとAVCとの関連と同等であった。

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Article, review, commentary, editorial, etc. (international conference proceedings)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

Background: Few studies have compared accurately measured office, self-measured home, and ambulatory blood pressure (BP) for asymptomatic intracranial artery stenosis (ICAS). Relationship of day-by-day or short-term variability in BP to asymptomatic ICAS remains unclear.

Objectives: To examine the association of office, home (mean value and day-by-day variability), and ambulatory BP indices (24-hour/daytime/nighttime mean values, short-term variability, nocturnal decline, and morning pressor surge) with asymptomatic ICAS.

Methods: Data on office and 7-day home BP and magnetic resonance angiography to assess ICAS were obtained in 677 men (mean age, 70.0 years) from a population-based cohort. Among them, 468 underwent 24-hour ambulatory BP monitoring. Mild- or severe-ICAS was defined as 1-49% or ≥50% stenosis, respectively, and any-ICAS as either mild or severe-ICAS.

Results: We observed mild- and severe-ICAS in 153 (22.6%) and 36 (5.3%) participants, respectively. In multivariable Poisson regression with robust error variance, higher systolic BP at office, home, or ambulatory BP monitoring was associated with the presence of any- or severe-ICAS. The associations with ICAS were comparable between office, home, and ambulatory systolic BP (all heterogeneity Ps &gt;0.1). Independent of mean systolic BP, greater nocturnal decline or morning pressor surge in systolic BP was associated with higher burden of any- or severe-ICAS.

Conclusion: The magnitude of association of BP accurately measured at office for asymptomatic ICAS was comparable with that of BP at home or ambulatory BP monitoring. Circadian BP variation based on ambulatory BP monitoring may be considered when assessing ICAS in apparently healthy individuals.

DOI： 10.1161/circ.143.suppl_1.p096

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<Highlight>●日本人男性集団において認知機能と空腹時血糖の関連を検討した。●認知機能はCASIで評価した。●糖尿病のない男性では血糖値が3.97-6.20mmol/Lの範囲で認知機能が最も高かった。●糖尿病のある男性では、血糖値が高いほど認知機能が低かった。●血糖値と認知機能との関連は糖尿病の有無により異なっていた。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J04763&link_issn=&doc_id=20200423300003&doc_link_id=10.2188%2Fjea.JE20180193&url=https%3A%2F%2Fdoi.org%2F10.2188%2Fjea.JE20180193&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(公社)日本産業衛生学会  

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Language：English   Publishing type：Article, review, commentary, editorial, etc. (international conference proceedings)   Publisher：(一社)日本動脈硬化学会  

一般日本人男性におけるMRIで評価した無症候性脳血管疾患(SCVD)と各種血圧指標、つまり収縮期血圧(SBP)、拡張期血圧(DBP)、脈圧、平均動脈圧(MAP)との関連について検討した。滋賀動脈硬化疫学研究にて第1期(2006〜2008年)と第2期(2010〜2014年)に診察室血圧と家庭血圧を測定し、第3期(2012〜2015年)にMRIを撮影した参加者616名のデータを用いた。MRI画像からSCVD[ラクナ梗塞、脳室周囲高信号域(PVH)、深部白質高信号域(DSWMH)、微小脳出血、頭蓋内動脈狭窄症(ICAS)]を評価した。多変数ロジスティック回帰分析により、診察室血圧1標準偏差増加毎のSCVDのオッズ比を推定した。家庭血圧についても同様の解析を行った。616名は第1期に平均63.6±9.2歳であった。第1期、第2期とも、診察室血圧の全指標とラクナ梗塞に関連がみられた。第1期、第2期のDBP、第1期のMAPはPVHとDSWMHと関連し、第1期のSBPはDSWMHと関連した。第2期の全血圧指標は第1期よりも微小脳出血と関連する傾向がみられ、第1期と第2期のSBP、脈圧、MAPとICASとの関連も同様であった。家庭血圧の解析で同様の結果が得られたが、有意性が低下したものもあった。以上から、一般日本人男性において血圧指標はほとんどのSCVDと関連していた。

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Authorship：Corresponding author   Language：English   Publishing type：Article, review, commentary, editorial, etc. (international conference proceedings)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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DOI： 10.1161/circ.141.suppl_1.P547

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Language：English   Publisher：Elsevier Scientific Publishers  

METHODS:In a prospective population-based study, 640 Japanese men were followed up for 5 years. The liver to spleen (L/S) ratio of the CT attenuation value was used as the liver fat accumulation index. We calculated the odds ratio (OR) and 95% confidence interval (CI) for the DM incidence of per 1 standard deviation (SD) lower L/S and those of L/S < 1.0 compared with L/S ≥ 1.0, using logistic regression models.

CiNii Article

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER DIABETES ASSOC  

DOI： 10.2337/db18-1636-P

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Language：Japanese   Publisher：(一社)日本老年医学会  

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BACKGROUND:The relationship between mutation locations in KCNQ1 which is a major gene in long QT syndrome (LQTS) and phenotype has been analyzed and used for risk stratification. Mutations in the transmembrane region (TM) or cytoplasmic-loop (C-loop) are associated with more frequent cardiac events than those in other regions. However, accumulation of LQTS type 1 (LQT1) patients poses the question of whether the location specific risk stratification is really effective. METHODS:The study cohort consisted of 67 KCNQ1 mutation carriers and 13 family members who were suspected as having LQTS due to sudden cardiac death or syncope from 36 unrelated families. The KCNQ1 mutations were L250H, V254M, H258P, and R259C located in segment 4-5 linker (C-loop), G269S, and S277L in segment 5 (TM). RESULTS:More than half of the patients with V254M or S277L suffered sudden cardiac death or syncope. In contrast, those with other mutations showed mild phenotype. In these two mutations related to severe phenotype, gender frequency and the age of onset were contrasting, 14 out of 23 patients with V254M were male, 19 out of 22 patients with S277L were female. In the patients we could confirm the age of onset, all of the patients with V254M showed symptoms at less than 15 years old, while 5 out of 12 patients with S277L suffered symptoms after 16 years old. CONCLUSION:Clinical characteristics were not specific for mutation locations but specific for respective mutations in our LQT1 patients. Patients should be evaluated by their own mutations to prevent severe cardiac events.

DOI： 10.1016/j.jjcc.2017.12.011

PubMed

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：Japanese   Publisher：(一社)日本循環器病予防学会  

【背景】客観的に評価された身体活動量がメタボリックシンドローム(MetS)発症リスクと関連するかどうか検討した研究はほとんどない。【目的】日本人一般住民男性において、歩数計を用いて評価された歩数値とMetS新規発症との関連を縦断的に検討すること。【方法】滋賀県草津市住民から無作為抽出された40-79歳男性のうちMetSを有さない525名(平均年齢64.1±9.6歳)を対象とし、5年間の前向きコホート研究(基礎調査2006-8年)を実施した。歩数は基礎調査時に土・日曜日を含む7日間連続で歩数計を用いて測定し1日平均値を求めた。MetS発症の診断は日本基準を用いて評価した。ロジスティック回帰を用いてMetS新規発症に対する歩数値に関する多変量調整相対リスク(RR)および95%信頼区間(CI)を算出した。【結果】平均追跡期間4.8±1.3年を経て、MetS新規発症者は77名(14.7%)であった。Body mass indexを含む交絡因子を調整後も歩数値とMetS発症との間に負の関連を認めた。この関連はMetS各構成要素でさらに調整しても変わらなかった(最低三分位群[5,792歩未満]と比較して、最高三分位群[10,033歩以上]のMetS発症に対するRR(95%CI)は0.34[0.17-0.72])。また、MetS発症に対する1日平均1,000歩増加あたりのRR(95%CI)は、0.87(0.78-0.96)であった。65歳未満・以上、MetS各構成要素の有無で層別に解析したが同様の傾向を認めた(全異質性P値>0.3)。【結語】MetSの好発集団とされる一般中高年男性において、客観的に評価された歩数値はMetS発症と有意な負の関連を示した。また、1日平均歩数値1,000歩増加あたりMetS発症リスクが13%低下した。本成果は健康日本21(第二次)の歩数目標値や身体活動基準2013を支持する結果である。(著者抄録)

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本循環器病予防学会  

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本循環器病予防学会