研究者詳細 - 三好　亨

論文 - 三好　亨

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Increased Circulating Malondialdehyde-Modified Low-Density Lipoprotein Level Is Associated with High-Risk Plaque in Coronary Computed Tomography Angiography in Patients Receiving Statin Therapy. 国際誌

Keishi Ichikawa, Toru Miyoshi, Kazuhiro Osawa, Takashi Miki, Hiroshi Ito

Journal of clinical medicine 10 ( 7 ) 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: To evaluate the association of serum malondialdehyde low-density lipoprotein (MDA-LDL), an oxidatively modified LDL, with the prevalence of high-risk plaques (HRP) determined with coronary computed tomography angiography (CTA) in statin-treated patients. METHODS: This study was a single-center retrospective cohort comprising 268 patients (mean age 67 years, 58% men) with statin therapy and who underwent coronary CTA for suspected stable coronary artery disease. Patients were classified into two groups according to median MDA-LDL level or median LDL-C level. Coronary CTA-verified HRP was defined when two or more characteristics, including positive remodeling, low-density plaques, and spotty calcification, were present. RESULTS: Patients with HRP had higher MDA-LDL (p = 0.011), but not LDL-C (p = 0.867) than those without HRP. High MDA-LDL was independently associated with HRP (odds ratio 1.883, 95% confidential interval 1.082-3.279) after adjustment for traditional risk factors. Regarding incremental value of MDA-LDL for predicting CTA-verified HRP, addition of serum MDA-LDL levels to the baseline model significantly increased global chi-square score from 26.1 to 32.8 (p = 0.010). CONCLUSIONS: A high serum MDA-LDL level is an independent predictor of CTA-verified HRP, which can lead to cardiovascular events in statin-treated patients.

DOI： 10.3390/jcm10071480

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Higher oxidized high-density lipoprotein to apolipoprotein A-I ratio is associated with high-risk coronary plaque characteristics determined by CT angiography. 国際誌

Kazuki Suruga, Toru Miyoshi, Kazuhiko Kotani, Keishi Ichikawa, Takashi Miki, Kazuhiro Osawa, Kentaro Ejiri, Hironobu Toda, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito

International journal of cardiology 324 193 - 198 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Oxidized high-density lipoprotein (oxHDL), unlike native HDL, is characterized by reduced cholesterol efflux capability and anti-inflammatory properties. The ratio of oxHDL to apolipoprotein A-I (oxHDL/apoAI) is a possible marker of dysfunctional HDL. The aim of this study was to evaluate the association between oxHDL/apoAI and coronary plaque characteristics that increase the likelihood of cardiovascular events as determined by coronary computed tomography (CT) angiography. METHODS: A total of 297 patients (mean age; 67 years, men; 63%) who underwent coronary CT angiography for suspected stable coronary artery disease (CAD) were included. High-risk plaques (HRP) were defined by three characteristics: positive remodeling; low-density plaques; and spotty calcification. Significant stenosis was defined as a luminal narrowing of >70%. Serum concentrations of oxHDL were measured using an enzyme-linked immunosorbent assay. RESULTS: Patients with higher oxHDL/ApoAI showed significantly greater prevalence of HRP (p = 0.03) and significant stenosis (p < 0.01) compared with patients with low oxHDL/ ApoAI. The multivariate logistic analysis demonstrated that oxHDL/ApoAI significantly associated with the presence of HRP and significant coronary stenosis (p = 0.01 and < 0.01). In the follow-up study including 243 patients for a median period of 1.8 years, univariate cox regression analysis showed that oxHDL/ApoAI, HRP and significant stenosis were significant predictors of cardiovascular events. CONCLUSIONS: A high oxHDL/apoAI was associated with the presence of HRP and significant stenosis determined by coronary CT angiography, which can lead to cardiovascular events in patients with suspected stable CAD.

DOI： 10.1016/j.ijcard.2020.09.060

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Possible Protective Effect of Remote Ischemic Preconditioning on Acute Kidney Injury Following Elective Percutaneous Coronary Intervention: Secondary Analysis of a Multicenter, Randomized Study.

Hiroaki Otsuka, Toru Miyoshi, Kentaro Ejiri, Kunihisa Kohno, Makoto Nakahama, Masayuki Doi, Mitsuru Munemasa, Masaaki Murakami, Kazufumi Nakamura, Hiroshi Ito

Acta medica Okayama 75 ( 1 ) 45 - 53 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Remote ischemic preconditioning (RIPC) is a promising strategy for protecting against ischemic reperfusion injury. This study is a secondary analysis of a randomized study that aimed to evaluate the effect of RIPC on the early increase in serum creatinine (SCr) following percutaneous coronary intervention (PCI), which is associ-ated with contrast-induced acute kidney injury. Patients with stable angina undergoing elective PCI were assigned to control, RIPC, and continuous infusion of nicorandil (nicorandil) groups. The endpoint of this study was the incidence of the early increase in SCr, a predictor of contrast-induced acute kidney injury, which was defined as either a > 20% or absolute increase by 0.3 mg/dl of SCr levels after 24 h of PCI. This study included 220 patients for whom a dataset of SCr values was available. The incidence of the early increase in SCr was significantly lower in the RIPC than in the control (1.3% vs 10.8%, p = 0.03) group, but was not significantly different between the nicorandil and control groups. In multivariate analysis, RIPC remained a significant fac-tor associated with a reduction in the incidence of early increase in SCr. RIPC reduces the incidence of early increase in SCr in patients with stable angina following elective PCI.

DOI： 10.18926/AMO/61433

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High Plasma Docosahexaenoic Acid Associated to Better Prognoses of Patients with Acute Decompensated Heart Failure with Preserved Ejection Fraction. 国際誌

Naoaki Matsuo, Toru Miyoshi, Atsushi Takaishi, Takao Kishinoue, Kentaro Yasuhara, Masafumi Tanimoto, Yukari Nakano, Nobuhiko Onishi, Masayuki Ueeda, Hiroshi Ito

Nutrients 13 ( 2 ) 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

The clinical relevance of polyunsaturated fatty acids (PUFAs) in heart failure remains unclear. The aim of this study was to investigate the association between PUFA levels and the prognosis of patients with heart failure with preserved ejection fraction (HFpEF). This retrospective study included 140 hospitalized patients with acute decompensated HFpEF (median age 84.0 years, 42.9% men). The patients' nutritional status was assessed, using the geriatric nutritional risk index (GNRI), and their plasma levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and dihomo-gamma-linolenic acid (DGLA) were measured before discharge. The primary outcome was all-cause mortality. During a median follow-up of 23.3 months, the primary outcome occurred in 37 patients (26.4%). A Kaplan-Meier analysis showed that lower DHA and DGLA levels, but not EPA or AA levels, were significantly associated with an increase in all-cause death (log-rank; p < 0.001 and p = 0.040, respectively). A multivariate Cox regression analysis also revealed that DHA levels were significantly associated with the incidence of all-cause death (HR: 0.16, 95% CI: 0.06-0.44, p = 0.001), independent of the GNRI. Our results suggest that low plasma DHA levels may be a useful predictor of all-cause mortality and potential therapeutic target in patients with acute decompensated HFpEF.

DOI： 10.3390/nu13020371

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Secular Decreasing Trend in Plasma Eicosapentaenoic and Docosahexaenoic Acids among Patients with Acute Coronary Syndrome from 2011 to 2019: A Single Center Descriptive Study. 国際誌

Tomoaki Okada, Toru Miyoshi, Masayuki Doi, Kosuke Seiyama, Wataru Takagi, Masahiro Sogo, Kazumasa Nosaka, Masahiko Takahashi, Keisuke Okawa, Hiroshi Ito

Nutrients 13 ( 1 ) 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Despite intensive lipid-lowering interventions, patients treated with statins develop atherosclerotic cardiovascular disease (ASCVD), and these patients have an increased risk of developing recurrent cardiovascular events during follow-up. Therefore, there is a need to focus on the residual risks in patients in statin therapy to further reduce ASCVD. The aim of this study was to retrospectively investigate the 10-year trend (2011-2019) regarding changes in polyunsaturated fatty acids (PUFAs) in patients with acute coronary syndrome (ACS) in a single center. We included 686 men and 203 women with ACS admitted to Kagawa Prefectural Central Hospital. Plasma PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and dihomo-γ-linolenic acid (DGLA), were measured at admission for suspected ACS. A secular decreasing trend in the levels of EPA and DHA and the EPA/AA ratio, but not of AA and DGLA, was observed. The analyses based on age (>70 or <70 years) and sex showed that the decreasing trend in the levels of EPA and DHA did not depend on age and remained significant only in men. Further studies are needed to obtain robust evidence to justify that the administration of n-3 PUFA contributes to the secondary prevention of ACS.

DOI： 10.3390/nu13010253

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Prognostic value of non-alcoholic fatty liver disease for predicting cardiovascular events in patients with diabetes mellitus with suspected coronary artery disease: a prospective cohort study. 国際誌

Keishi Ichikawa, Toru Miyoshi, Kazuhiro Osawa, Takashi Miki, Hironobu Toda, Kentaro Ejiri, Masatoki Yoshida, Yusuke Nanba, Masashi Yoshida, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito

Cardiovascular diabetology 20 ( 1 ) 8 - 8 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Risk stratification of cardiovascular events in patients with type 2 diabetes mellitus (T2DM) has not been established. Coronary artery calcium score (CACS) and non-alcoholic fatty liver disease (NAFLD) are independently associated with cardiovascular events in T2DM patients. This study examined the incremental prognostic value of NAFLD assessed by non-enhanced computed tomography (CT) in addition to CACS and Framingham risk score (FRS) for cardiovascular events in T2DM patients. METHODS: This prospective pilot study included 529 T2DM outpatients with no history of cardiovascular disease who underwent CACS measurement because of suspected coronary artery disease. NAFLD was defined on CT images as a liver:spleen attenuation ratio < 1.0. Cardiovascular events were defined as cardiovascular death, nonfatal myocardial infarction, late coronary revascularization, nonfatal stroke, or hospitalization for heart failure. RESULTS: Among 529 patients (61% men, mean age 65 years), NAFLD was identified in 143 (27%). Forty-four cardiovascular events were documented during a median follow-up of 4.4 years. In multivariate Cox regression analysis, NAFLD, CACS, and FRS were associated with cardiovascular events (hazard ratios and 95% confidence intervals 5.43, 2.82-10.44, p < 0.001; 1.56, 1.32-1.86, p < 0.001; 1.23, 1.08-1.39, p = 0.001, respectively). The global χ2 score for predicting cardiovascular events increased significantly from 27.0 to 49.7 by adding NAFLD to CACS and FRS (p < 0.001). The addition of NAFLD to a model including CACS and FRS significantly increased the C-statistic from 0.71 to 0.80 (p = 0.005). The net reclassification achieved by adding CACS and FRS was 0.551 (p < 0.001). CONCLUSIONS: NAFLD assessed by CT, in addition to CACS and FRS, could be useful for identifying T2DM patients at higher risk of cardiovascular events.

DOI： 10.1186/s12933-020-01192-4

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Lack of collagen α6(IV) chain in mice does not cause severe-to-profound hearing loss or cochlear malformation, a distinct phenotype from nonsyndromic hearing loss with COL4A6 missense mutation. 国際誌

Shaoying Tang, Tomoko Yonezawa, Yukihide Maeda, Mitsuaki Ono, Takahiro Maeba, Toru Miyoshi, Ryusuke Momota, Yasuko Tomono, Toshitaka Oohashi

PloS one 16 ( 4 ) e0249909 2021年

記述言語：英語掲載種別：研究論文（学術雑誌）

Congenital hearing loss affects 1 in every 1000 births, with genetic mutations contributing to more than 50% of all cases. X-linked nonsyndromic hereditary hearing loss is associated with six loci (DFNX1-6) and five genes. Recently, the missense mutation (c.1771G>A, p.Gly591Ser) in COL4A6, encoding the basement membrane (BM) collagen α6(IV) chain, was shown to be associated with X-linked congenital nonsyndromic hearing loss with cochlear malformation. However, the mechanism by which the COL4A6 mutation impacts hereditary hearing loss has not yet been elucidated. Herein, we investigated Col4a6 knockout (KO) effects on hearing function and cochlear formation in mice. Immunohistochemistry showed that the collagen α6(IV) chain was distributed throughout the mouse cochlea within subepithelial BMs underlying the interdental cells, inner sulcus cells, basilar membrane, outer sulcus cells, root cells, Reissner's membrane, and perivascular BMs in the spiral limbus, spiral ligament, and stria vascularis. However, the click-evoked auditory brainstem response analysis did not show significant changes in the hearing threshold of Col4a6 KO mice compared with wild-type (WT) mice with the same genetic background. In addition, the cochlear structures of Col4a6 KO mice did not exhibit morphological alterations, according to the results of high-resolution micro-computed tomography and histology. Hence, loss of Col4a6 gene expression in mice showed normal click ABR thresholds and normal cochlear formation, which differs from humans with the COL4A6 missense mutation c.1771G>A, p.Gly591Ser. Therefore, the deleterious effects in the auditory system caused by the missense mutation in COL4A6 are likely due to the dominant-negative effects of the α6(IV) chain and/or α5α6α5(IV) heterotrimer with an aberrant structure that would not occur in cases with loss of gene expression.

DOI： 10.1371/journal.pone.0249909

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Early Initiation of Evolocumab Markedly Reduces Low-Density Lipoprotein Cholesterol Levels After Myocardial Infarction. 国際誌

Tomoaki Okada, Masayuki Doi, Toru Miyoshi, Kazumasa Nosaka, Satoshi Taya, Keisuke Yamamoto, Ai Sakamoto, Satoko Ugawa, Ryu Tsushima, Hiroshi Ito

JACC. Cardiovascular interventions 13 ( 24 ) 2944 - 2946 2020年12月

Correction to: Combination therapy with pemafibrate (K-877) and pitavastatin improves vascular endothelial dysfunction in dahl/salt-sensitive rats fed a high-salt and high-fat diet. 国際誌

Masatoki Yoshida, Kazufumi Nakamura, Toru Miyoshi, Masashi Yoshida, Megumi Kondo, Kaoru Akazawa, Tomonari Kimura, Hiroaki Ohtsuka, Yuko Ohno, Daiji Miura, Hiroshi Ito

Cardiovascular diabetology 19 ( 1 ) 213 - 213 2020年12月

Improvement in renal and endothelial function after catheter ablation in patients with persistent atrial fibrillation 査読

Okawa K, Miyoshi T, Sogo M, Hara S, Sudo Y, Ugawa S, Takahashi M, Doi M, Morita H, Ito H

J Cardiol 76 ( 6 ) 610 - 617 2020年12月

Improvement in renal and endothelial function after catheter ablation in patients with persistent atrial fibrillation. 国際誌

Keisuke Okawa, Toru Miyoshi, Masahiro Sogo, Shohei Hara, Yuya Sudo, Satoko Ugawa, Masahiko Takahashi, Masayuki Doi, Hiroshi Morita, Hiroshi Ito

Journal of cardiology 76 ( 6 ) 610 - 617 2020年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Cardiovascular events in patients with atrial fibrillation (AF) can be lowered by catheter ablation. We hypothesized the underlying mechanism was improvement in renal and endothelial function corresponding to AF burden, and investigated whether restoration of sinus rhythm (SR) after ablation affected these functions according to AF type. METHODS AND RESULTS: We prospectively measured estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), and reactive hyperemia index (RHI) in 358 consecutive patients with AF before and 6 and 12 months after the ablation. For each AF type [paroxysmal AF (PAF), n = 229, and persistent AF (PeAF), n = 129], we evaluated changes in these markers and influence of chronic kidney disease (CKD). The eGFR and natural logarithm-transformed (ln) UACR improved at 6 months in the PeAF group (68.7 ± 18.7-71.8 ± 18.9 mL/min/1.73 m2, p = 0.003 and 3.1±1.6 to 2.8±1.5, p < 0.001, respectively) and remained unchanged in the PAF group. Among the PeAF patients, recurrent AF was identified in 41, but only transiently in 38 patients. PeAF at baseline independently predicted increased eGFR [odds ratio (OR)=2.13, 95 % confidence interval (CI) 1.35-3.40, p = 0.001] and decreased UACR (OR=1.94, 95 % CI 1.05-3.58, p = 0.033). In the PeAF patients with CKD, ln-RHI significantly increased at 6 months after the ablation, and the change (Δ) in ln-RHI was significantly correlated with the ΔeGFR (r=0.35, p = 0.03). CONCLUSIONS: SR restoration after ablation was associated with an improved eGFR and UACR in PeAF patients, but not PAF patients. In PeAF patients with CKD, an improved endothelial function after ablation was associated with an improved renal function.

DOI： 10.1016/j.jjcc.2020.07.002

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Cardio-Ankle Vascular Index and Atrial Remodeling for Atrial Fibrillation 査読

Miyoshi T

J Atheroscler Thromb 2020年11月

Chemoradiation therapy for non-small cell lung cancer exacerbates thoracic aortic calcification determined by computed tomography 査読

Miki T, Miyauchi S, Miyoshi T, Yoshida M, Ichikawa K, Soh J, Nakamura K, Kiura K, Kanazawa S, Toyooka S, Ito H

Heart Vessels 35 ( 10 ) 1401 - 1408 2020年10月

Ischemic Myocardial Burden Subtended by Computed Tomography-Derived Fractional Flow Reserve (APPROACHFFRCT): An Exploratory Analysis on Diagnostic Performance 査読

Ihdayhid AR, Norgaard BL, Achenbach S, Khav N, Gaur S, Leipsic J, Nerlekar N, Osawa K, Miyoshi T, Jensen JM, Kimura T, Shiomi H, Erglis A, Oldroyd KG, Botker HE, Narula J, Ko BS

JACC Cardiovasc Imaging 13 ( 10 ) 2264 - 2267 2020年10月

Ischemic Myocardial Burden Subtended by Computed Tomography-Derived Fractional Flow Reserve (APPROACHFFRCT): An Exploratory Analysis on Diagnostic Performance. 国際誌

Abdul Rahman Ihdayhid, Bjarne L Norgaard, Stephan Achenbach, Nancy Khav, Sara Gaur, Jonathan Leipsic, Nitesh Nerlekar, Kazuhiro Osawa, Toru Miyoshi, Jesper M Jensen, Takeshi Kimura, Hiroki Shiomi, Andrejs Erglis, Keith G Oldroyd, Hans Erik Botker, Jagat Narula, Brian S Ko

JACC. Cardiovascular imaging 13 ( 10 ) 2264 - 2267 2020年10月

Chemoradiation therapy for non-small cell lung cancer exacerbates thoracic aortic calcification determined by computed tomography.

Takashi Miki, Shunsaku Miyauchi, Toru Miyoshi, Masashi Yoshida, Keishi Ichikawa, Junichi Soh, Kazufumi Nakamura, Katsuyuki Kiura, Susumu Kanazawa, Shinichi Toyooka, Hiroshi Ito

Heart and vessels 35 ( 10 ) 1401 - 1408 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Preoperative chemoradiation therapy (CRT) has been considered as an effective treatment for non-small cell lung cancer. However, there is concern that CRT progresses atherosclerosis in cancer survivors. This study sought to determine if preoperative CRT exacerbated thoracic aortic calcification (TAC) detected by computed tomography (CT) in patients with lung cancer. Among 473 patients who underwent surgery for lung cancer at Okayama University Hospital between 2011 and 2015, 34 patients undergoing preoperative CRT and surgery (CRT group) and 33 matched patients undergoing initial surgery (non-CRT group) were analyzed and compared. The volume of TAC between the 2nd and 12th thoracic vertebrae was quantitatively measured by CT at baseline and 1-year follow-up. Patients in the CRT group (62 ± 7 years old, 74% male) received cisplatin chemotherapy with docetaxel or vinorelbine and radiation therapy (mean 47.3 ± 4.0 Gy). The percent change in TAC volume was significantly greater in the CRT compared with the non-CRT group (58.7%, 95% confidence interval [CI] 41.7-75.7% vs. 27.2%, 95% CI 9.9-44.4%; p = 0.01). Multivariate logistic regression analysis identified CRT as an independent factor associated with greater TAC progression (> the median value) (odds ratio 3.63, 95% CI 1.19-11.08; p = 0.02). In conclusion, preoperative CRT for lung cancer exacerbates TAC. Follow-up of such patients should thus include careful longitudinal assessment for cardiovascular disease.

DOI： 10.1007/s00380-020-01611-2

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Combination therapy with pemafibrate (K-877) and pitavastatin improves vascular endothelial dysfunction in dahl/salt-sensitive rats fed a high-salt and high-fat diet 査読

Yoshida M, Nakamura K, Miyoshi T, Yoshida M, Kondo M, Akazawa K, Kimura T, Ohtsuka H, Ohno Y, Miura D, Ito H

Cardiovasc Diabetol 19 ( 1 ) 149 2020年9月

Combination therapy with pemafibrate (K-877) and pitavastatin improves vascular endothelial dysfunction in dahl/salt-sensitive rats fed a high-salt and high-fat diet. 国際誌

Masatoki Yoshida, Kazufumi Nakamura, Toru Miyoshi, Masashi Yoshida, Megumi Kondo, Kaoru Akazawa, Tomonari Kimura, Hiroaki Ohtsuka, Yuko Ohno, Daiji Miura, Hiroshi Ito

Cardiovascular diabetology 19 ( 1 ) 149 - 149 2020年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Statins suppress the progression of atherosclerosis by reducing low-density lipoprotein (LDL) cholesterol levels. Pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor α modulator, is expected to reduce residual risk factors including high triglycerides (TGs) and low high-density lipoprotein (HDL) cholesterol during statin treatment. However, it is not known if statin therapy with add-on pemafibrate improves the progression of atherosclerosis. The aim of this study was to assess the effect of combination therapy with pitavastatin and pemafibrate on lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats. METHODS: Seven-week-old male Dahl salt-sensitive (DS) rats were divided into the following five treatment groups (normal diet (ND) plus vehicle, high-salt and high-fat diet (HD) plus vehicle, HD plus pitavastatin (0.3 mg/kg/day), HD plus pemafibrate (K-877) (0.5 mg/kg/day), and HD plus combination of pitavastatin and pemafibrate) and treated for 12 weeks. At 19 weeks, endothelium-dependent relaxation of the thoracic aorta in response to acetylcholine was evaluated. RESULTS: After feeding for 12 weeks, systolic blood pressure and plasma levels of total cholesterol were significantly higher in the HD-vehicle group compared with the ND-vehicle group. Combination therapy with pitavastatin and pemafibrate significantly reduced systolic blood pressure, TG levels, including total, chylomicron (CM), very LDL (VLDL), HDL-TG, and cholesterol levels, including total, CM, VLDL, and LDL-cholesterol, compared with vehicle treatment. Acetylcholine caused concentration-dependent relaxation of thoracic aorta rings that were pre-contracted with phenylephrine in all rats. Relaxation rates in the HD-vehicle group were significantly lower compared with the ND-vehicle group. Relaxation rates in the HD-combination of pitavastatin and pemafibrate group significantly increased compared with the HD-vehicle group, although neither medication alone ameliorated relaxation rates significantly. Western blotting experiments showed increased phosphorylated endothelial nitric oxide synthase protein expression in aortas from rats in the HD-pemafibrate group and the HD-combination group compared with the HD-vehicle group. However, the expression levels did not respond significantly to pitavastatin alone. CONCLUSIONS: Combination therapy with pitavastatin and pemafibrate improved lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats. Pemafibrate as an add-on strategy to statins may be useful for preventing atherosclerosis progression.

DOI： 10.1186/s12933-020-01132-2

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Effect of Luseogliflozin on Heart Failure With Preserved Ejection Fraction in Patients With Diabetes Mellitus 査読

Ejiri K, Miyoshi T, Kihara H, Hata Y, Nagano T, Takaishi A, Toda H, Nanba S, Nakamura Y, Akagi S, Sakuragi S, Minagawa T, Kawai Y, Nishii N, Fuke S, Yoshikawa M, Nakamura K, Ito H; MUSCAT‐HF Study Investigators

J Am Heart Assoc 9 ( 16 ) e015103 2020年8月

Effect of Luseogliflozin on Heart Failure With Preserved Ejection Fraction in Patients With Diabetes Mellitus. 国際誌

Kentaro Ejiri, Toru Miyoshi, Hajime Kihara, Yoshiki Hata, Toshihiko Nagano, Atsushi Takaishi, Hironobu Toda, Seiji Nanba, Yoichi Nakamura, Satoshi Akagi, Satoru Sakuragi, Taro Minagawa, Yusuke Kawai, Nobuhiro Nishii, Soichiro Fuke, Masaki Yoshikawa, Kazufumi Nakamura, Hiroshi Ito

Journal of the American Heart Association 9 ( 16 ) e015103 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background Effects of sodium-glucose cotransporter 2 inhibitors on reducing hospitalization for heart failure have been reported in randomized controlled trials, but their effects on patients with heart failure with preserved ejection fraction (HFpEF) are unknown. This study aimed to evaluate the drug efficacy of luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, in patients with type 2 diabetes mellitus and HFpEF. Methods and Results We performed a multicenter, open-label, randomized, controlled trial for comparing luseogliflozin 2.5 mg once daily with voglibose 0.2 mg 3 times daily in patients with type 2 diabetes mellitus suffering from HFpEF (left ventricular ejection fraction >45% and BNP [B-type natriuretic peptide] concentrations ≥35 pg/mL) in a 1:1 randomization fashion. The primary outcome was the difference from baseline in BNP levels after 12 weeks of treatment between the 2 drugs. A total of 173 patients with diabetes mellitus and HFpEF were included. Of these, 83 patients were assigned to receive luseogliflozin and 82 to receive voglibose. There was no significant difference in the reduction in BNP concentrations after 12 weeks from baseline between the 2 groups. The ratio of the mean BNP value at week 12 to the baseline value was 0.79 in the luseogliflozin group and 0.87 in the voglibose group (percent change, -9.0% versus -1.9%; ratio of change with luseogliflozin versus voglibose, 0.93; 95% CI, 0.78-1.10; P=0.26). Conclusion In patients with type 2 diabetes mellitus and HFpEF, there is no significant difference in the degree of reduction in BNP concentrations after 12 weeks between luseogliflozin and voglibose. Registration URL: https://www.umin.ac.jp/ctr/index.htm; Unique identifier: UMIN000018395.

DOI： 10.1161/JAHA.119.015103

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