Faculty Profiles - NAKAMURA Kazufumi

Papers - NAKAMURA Kazufumi

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The number of circulating CD34-positive cells is an independent predictor of coronary artery calcification progression: Sub-analysis of a prospective multicenter study. Reviewed International journal

Keishi Ichikawa, Toru Miyoshi, Kazuhiro Osawa, Takashi Miki, Kunihisa Kohno, Kazufumi Nakamura, Yasushi Koyama, Hiroshi Ito

Cardiology journal 2022.3

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

BACKGROUND: Decreases in circulating CD34-positive cells are associated with increases in cardiovascular events. We investigated the association between the number of CD34-positive cells and the progression of coronary artery calcification (CAC), a marker of atherosclerosis, in patients with hypercholesteremia under statin therapy in a sub-analysis of a multicenter study. METHODS: In the principal study, patients with CAC scores of 1-999 were treated with pitavastatin. Measurement of CAC by non-enhanced computed tomography and a blood test were performed at baseline and at 1-year follow-up. Patients were divided into two groups: CAC progression (change in CAC score > 0) and non-progression. The number of circulating CD34-positive cells was counted using flow cytometry. RESULTS: A total of 156 patients (mean age 67 years, 55% men) were included in this sub-analysis. CD34 positive cell numbers at baseline as a continuous variable was inversely correlated with annual change in the log-transformed CAC score (r = -0.19, p = 0.02). When patients were divided into high and low CD34 groups based on the median value of 0.8 cells/μL, the adjusted change in CAC score in the low-CD34 group was significantly greater than that in the high-CD34 group (54.2% vs. 20.8%, respectively, p = 0.04). In multiple logistic analysis, a low CD34-positive cell number was an independent predictor of CAC progression, with an odds ratio of 2.88 (95% confidence interval 1.28-6.49, p = 0.01). CONCLUSIONS: Low numbers of CD34-positive cells are associated with CAC progression in patients with hypercholesterolemia under statin therapy. The number of CD34-positive cells may help to identify patients at increased cardiovascular risk.

DOI： 10.5603/CJ.a2021.0151

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Fragmented QRS as a predictor of cardiac events in patients with cardiac sarcoidosis. Reviewed International journal

Soichiro Ogura, Kazufumi Nakamura, Hiroshi Morita, Koji Nakagawa, Nobuhiro Nishii, Satoshi Akagi, Norihisa Toh, Yoichi Takaya, Masashi Yoshida, Toru Miyoshi, Atsuyuki Watanabe, Hiroshi Ito

Journal of cardiology 79 ( 3 ) 446 - 452 2022.3

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

BACKGROUND: Multiple spikes within the QRS complex, known as fragmented QRS (fQRS), are associated with the occurrences of ventricular arrhythmic events (VAEs) in patients with Brugada syndrome and hypertrophic cardiomyopathy. However, the association between fQRS and occurrence of VAEs in patients with cardiac sarcoidosis (CS) has not been elucidated. METHODS: We evaluated the associations between fQRS and cardiac events including VAEs [non-sustained ventricular tachycardia (NSVT), sustained ventricular tachycardia (VT), and ventricular fibrillation (VF)], hospitalization for heart failure, and all-cause death in 68 patients with CS (30 patients with fQRS vs. 38 patients without fQRS) over a 5-year period. RESULTS: Cardiac events occurred in 22 patients with fQRS and 18 patients without fQRS (73% vs. 47%, p=0.009). Of the cardiac events that occurred in CS patients, VAEs occurred more frequently in patients with fQRS than in patients without fQRS (VAEs: 70% vs. 45%, p=0.017; NSVT: 70% vs. 45%, p=0.010; VT: 43% vs. 18%, p=0.011, and VF: 6.7% vs. 2.6%, p=0.34), whereas there was no significant difference in hospitalization for heart failure or all-cause death between patients with and those without fQRS (hospitalization for heart failure: 6.7% vs. 5.3%, p=0.75; all-cause death: 6.7% vs. 5.3%, p=0.64). Multivariate analysis showed that fQRS in the baseline electrocardiogram was independently associated with VAEs (hazard ratio: 2.21, 95% confidence interval: 1.15-4.25, p=0.017). CONCLUSION: fQRS is a predictor of VAEs in patients with CS.

DOI： 10.1016/j.jjcc.2021.10.022

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Effects of luseogliflozin on estimated plasma volume in patients with heart failure with preserved ejection fraction. Reviewed International journal

Mitsutaka Nakashima, Toru Miyoshi, Kentaro Ejiri, 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

ESC heart failure 9 ( 1 ) 712 - 720 2022.2

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

AIMS: Sodium glucose co-transporter 2 inhibitors have diuretic effects in both patients with glycosuria and with natriuresis. We sought to assess the effect of luseogliflozin on estimated plasma volume (ePV) in patients with type 2 diabetes and heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: This study was a post-hoc analysis of the MUSCAT-HF trial (UMIN000018395), a multicentre, prospective, open-label, randomized controlled trial that assessed the effect of 12 weeks of luseogliflozin (2.5 mg, once daily, n = 83) as compared with voglibose (0.2 mg, three times daily, n = 82) on the reduction in brain natriuretic peptide (BNP) in patients with type 2 diabetes and HFpEF. The analysis compared the change in ePV calculated by the Straus formula from baseline to Weeks 4, 12, and 24, using a mixed-effects model for repeated measures. We also estimated the association between changes in ePV and changes in other clinical parameters, including BNP levels. Luseogliflozin significantly reduced ePV as compared to voglibose at Week 4 {adjusted mean group-difference -6.43% [95% confidence interval (CI): -9.11 to -3.74]}, at Week 12 [-8.73% (95%CI: -11.40 to -6.05)], and at Week 24 [-11.02% (95%CI: -13.71 to -8.33)]. The effect of luseogliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in ePV at Week 12 was significantly associated with log-transformed BNP (r = 0.197, P = 0.015) and left atrial volume index (r = 0.283, P = 0.019). CONCLUSIONS: Luseogliflozin significantly reduced ePV in patients with type 2 diabetes and HFpEF, as compared with voglibose. The reduction of intravascular volume by luseogliflozin may provide clinical benefits to patients with type 2 diabetes and HFpEF.

DOI： 10.1002/ehf2.13683

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2型糖尿病患者におけるCTを用いた冠動脈周囲脂肪の炎症イメージングによるリスク評価

市川啓之, 三好亨, 中島充貴, 西原大裕, 三木崇史, 中村一文, 森田宏, 伊藤浩

日本内科学会雑誌 111 ( 臨増 ) 158 - 158 2022.2

Incremental prognostic value of non-alcoholic fatty liver disease over coronary computed tomography angiography findings in patients with suspected coronary artery disease. Reviewed International journal

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

European journal of preventive cardiology 2022.1

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

AIMS: This study aimed to investigate additional risk stratification benefits of hepatic steatosis (HS) concurrently assessed during coronary computed tomography angiography (CTA) in a large patient cohort with suspected stable coronary artery disease (CAD). METHODS AND RESULTS: In this prospective study, 1148 Japanese outpatients without a history of CAD who underwent coronary CTA for suspected stable CAD (mean age 64 ± 14 years) were included. HS, defined on CT as a hepatic-to-spleen attenuation ratio of <1.0, was examined just before the evaluation of adverse CTA findings, defined as obstructive and/or high-risk plaque. The major adverse cardiac events (MACE) were the composite of cardiac death, acute coronary syndrome, and late revascularization. The incremental predictive value of HS was evaluated using the global χ2 test and C-statistic. HS was identified in 247 (22%) patients. During a median follow-up of 3.9 years, MACE was observed in 40 (3.5%) patients. HS was significantly associated with MACE in a model that included adverse CTA findings (hazard ratio 4.01, 95% confidence interval 2.12-7.59, P < 0.001). By adding HS to the Framingham risk score and adverse CTA findings, the global χ2 score and C-statistic significantly increased from 29.0 to 49.5 (P < 0.001) and 0.74 to 0.81 (P = 0.026), respectively. In subgroup analyses in patients with diabetes mellitus and metabolic syndrome, HS had significant additive predictive value for MACE over the Framingham risk score and adverse CTA findings. CONCLUSION: In patients with suspected stable CAD, concurrent evaluation of HS during coronary CTA enables more accurate detection of patients at higher risk of MACE.

DOI： 10.1093/eurjpc/zwab120

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Assessment of congestion and clinical outcomes in patients with chronic heart failure using shear wave elasticity Reviewed

Rie Nakayama, Yoichi Takaya, Kazufumi Nakamura, Rika Takemoto, Norihisa Toh, Hiroshi Ito

ESC Heart Failure 9 ( 2 ) 1279 - 1286 2022.1

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

Abstract

Aims

The relief of congestion is essential for the prevention of worsening heart failure (HF) resulting in hospitalizations. Assessment of the degree of organ congestion in the chronic phase of HF is important for determining therapeutic strategies. The aim of this study was to evaluate the efficacy of shear wave (SW) elasticity for assessing congestion and clinical outcomes in patients with chronic HF.

Methods and results

We prospectively enrolled 345 consecutive patients with chronic HF who underwent SW elastography at outpatient clinic. Patients were divided into two groups according to the median value of SW elasticity: low group (SW elasticity <6.4 kPa, n = 176) and high group (SW elasticity ≥6.4 kPa, n = 169). The endpoint was cardiovascular death or hospitalization for HF. During the median follow‐up period of 19 months (range: 7–36 months), cardiovascular death or hospitalization for HF occurred in 4 patients of low group and 27 patients of high group. In high group, 8 patients died, and 19 patients were hospitalized for HF. In low group, 3 patients died, and 1 patient was hospitalized. Kaplan–Meier analysis showed that the event‐free survival rate was worse in high group than in low group (log‐rank test, P = 0.004). After adjusting for variables, high SW elasticity was independently related to cardiac events. In multivariate regression analysis, SW elasticity was correlated with left atrial volume index, early diastolic mitral inflow velocity to mitral annular velocity ratio, and inferior vena cava diameter.

Conclusions

The SW elasticity reflected haemodynamic congestion in patients with chronic HF, which was related to cardiac events.

DOI： 10.1002/ehf2.13809

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ehf2.13809

Rapidly Progressive Stenosis of the Left Main Trunk Ostium Starting 21 Months After Stent Implantation Reviewed

Y. Naito, M. Yoshikawa, K. Nakamura, M. Kubo, H. Sugiyama, H. Suzuki

Acta Med Okayama 76 ( 1 ) 99 - 104 2022.1

Pemafibrate Prevents Rupture of Angiotensin II-Induced Abdominal Aortic Aneurysms. Reviewed International journal

Naofumi Amioka, Toru Miyoshi, Tomoko Yonezawa, Megumi Kondo, Satoshi Akagi, Masashi Yoshida, Yukihiro Saito, Kazufumi Nakamura, Hiroshi Ito

Frontiers in cardiovascular medicine 9 904215 - 904215 2022

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

Background: Abdominal aortic aneurysm (AAA) is a life-threatening disease that lacks effective preventive therapies. This study aimed to evaluate the effect of pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPARα) agonist, on AAA formation and rupture. Methods: Experimental AAA was induced by subcutaneous angiotensin II (AngII) infusion in ApoE - / - mice for 4 weeks. Pemafibrate (0.1 mg/kg/day) was administered orally. Dihydroethidium staining was used to evaluate the reactive oxygen species (ROS). Results: The size of the AngII-induced AAA did not differ between pemafibrate- and vehicle-treated groups. However, a decreased mortality rate due to AAA rupture was observed in pemafibrate-treated mice. Pemafibrate ameliorated AngII-induced ROS and reduced the mRNA expression of interleukin-6 and tumor necrosis factor-α in the aortic wall. Gelatin zymography analysis demonstrated significant inhibition of matrix metalloproteinase-2 activity by pemafibrate. AngII-induced ROS production in human vascular smooth muscle cells was inhibited by pre-treatment with pemafibrate and was accompanied by an increase in catalase activity. Small interfering RNA-mediated knockdown of catalase or PPARα significantly attenuated the anti-oxidative effect of pemafibrate. Conclusion: Pemafibrate prevented AAA rupture in a murine model, concomitant with reduced ROS, inflammation, and extracellular matrix degradation in the aortic wall. The protective effect against AAA rupture was partly mediated by the anti-oxidative effect of catalase induced by pemafibrate in the smooth muscle cells.

DOI： 10.3389/fcvm.2022.904215

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Molecular Mechanisms of Cardiac Amyloidosis. Reviewed International journal

Yukihiro Saito, Kazufumi Nakamura, Hiroshi Ito

International journal of molecular sciences 23 ( 1 ) 2021.12

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

Cardiac involvement has a profound effect on the prognosis of patients with systemic amyloidosis. Therapeutic methods for suppressing the production of causative proteins have been developed for ATTR amyloidosis and AL amyloidosis, which show cardiac involvement, and the prognosis has been improved. However, a method for removing deposited amyloid has not been established. Methods for reducing cytotoxicity caused by amyloid deposition and amyloid precursor protein to protect cardiovascular cells are also needed. In this review, we outline the molecular mechanisms and treatments of cardiac amyloidosis.

DOI： 10.3390/ijms23010025

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心内膜心筋生検による心臓サルコイドーシスの診断(Diagnosis of Cardiac Sarcoidosis by Endomyocardial Biopsy)

中村一文, 網岡尚史, 中川晃志, 赤木達, 伊藤浩

日本循環器学会学術集会抄録集 85回 SS05 - 3 2021.3

Effects of Dual Initial Combination Therapy With Macitentan Plus Riociguat or Macitentan Plus Selexipag on Hemodynamics in Patients With Pulmonary Arterial Hypertension (SETOUCHI-PH Study) - Protocol of a Multicenter Randomized Control Trial.

Satoshi Akagi, Yoshihiro Dohi, Kaori Ishikawa, Kayoko Kubota, Koshin Horimoto, Shusuke Yagi, Tetsuo Hirata, Eiichiro Yamamoto, Hiroshi Ito, Kazufumi Nakamura

Circulation reports 3 ( 2 ) 105 - 109 2021.1

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

Background: The latest guideline from the European Society of Cardiology and European Respiratory Society recommends initial combination therapy with oral pulmonary arterial hypertension (PAH)-specific drugs in PAH patients with World Health Organization functional class (WHO-FC) II or III. However, whether this initial combination therapy improves hemodynamics and clinical failure events regardless of the combination of PAH-specific drugs remains unknown. This study was designed to evaluate whether the initial combination therapy with macitentan plus riociguat or macitentan plus selexipag showed equal efficacy in reducing pulmonary vascular resistance (PVR) 8 months after administration. Methods and Results: This study is a multicenter randomized control trial. PAH subjects with WHO-FC II or III will be randomized (1 : 1) into initial combination therapy with either macitentan plus riociguat or macitentan plus selexipag, and will be observed 8 months after the initiation of treatment. The primary endpoint will be the difference in the change ratio of PVR from baseline to after 8 months of treatment. Conclusions: The SETOUCHI-PH study will clarify whether initial combination therapy with macitentan plus riociguat or macitentan plus selexipag results in equal reductions in PVR 8 months after administration.

DOI： 10.1253/circrep.CR-20-0133

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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. International journal

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 2021.1

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

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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Usefulness of right ventriculography compared with computed tomography for ruling out the possibility of lead perforation before lead extraction. International journal

Saori Asada, Nobuhiro Nishii, Takayoshi Shinya, Akihito Miyoshi, Yoshimasa Morimoto, Masakazu Miyamoto, Koji Nakagawa, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito

PloS one 16 ( 3 ) e0245502 2021

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

PURPOSE: High-risk patients can be identified by preprocedural computed tomography (CT) before lead extraction. However, CT evaluation may be difficult especially for lead tip identification due to artifacts in the leads. Selective right ventriculography (RVG) may enable preprocedural evaluation of lead perforation. We investigated the efficacy of RVG for identifying right ventricular (RV) lead perforation compared with CT in patients who underwent lead extraction. METHODS: Ninety-five consecutive patients who were examined by thin-section non-ECG-gated multidetector CT and RVG before lead extraction were investigated retrospectively. Newly recognized pericardial effusion after lead extraction was used as a reference standard for lead perforation. We analyzed the prevalence of RV lead perforation diagnosed by each method. The difference in the detection rates of lead perforation by RVG and CT was evaluated. RESULTS: Of the 115 RV leads in the 95 patients, lead perforation was diagnosed for 35 leads using CT, but the leads for 29 (83%) of those 35 leads diagnosed as lead perforation by CT were shown to be within the right ventricle by RVG. Three patients with 5 leads could not be evaluated by CT due to motion artifacts. The diagnostic accuracies of RVG and CT were significantly different (p < 0.001). There was no complication of pericardial effusion caused by RV lead extraction. CONCLUSION: RVG for identification of RV lead perforation leads to fewer false-positives compared to non-ECG-gated CT. However, even in cases in which lead perforation is diagnosed, most leads may be safely extracted by transvenous lead extraction.

DOI： 10.1371/journal.pone.0245502

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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. International journal

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 2020.12

心アミロイドーシスの療総論 (心不全, 不整脈, 血栓塞栓症に対する治療)

宮本真和, 中村一文

24 ( 11 ) 1078 - 1083 2020.11

救急外来での見逃し(Missed)を避けるべき心原性失神10 real cases approach

藤本竜平, 森田宏, 間瀬浩, 三木崇史, 戸田洋伸, 杜徳尚, 西井伸洋, 中村一文, 鈴木洋, 伊藤浩

日本救急医学会雑誌 31 ( 11 ) 2280 - 2280 2020.11

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

Heart Vessels 35 ( 10 ) 1401 - 1408 2020.10

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 Reviewed

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 2020.9

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. International journal

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 2020.9

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

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 Reviewed

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 2020.8

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Papers - NAKAMURA Kazufumi