title: Impact of hypertriglyceridemia on endothelial dysfunction during statin ± ezetimibe therapy in patients with coronary heart disease.
abstract: Despite the use of statin therapy and achieving the target for low-density lipoprotein cholesterol, a substantial number of coronary events are not prevented, and residual risk factors remain unsettled. Recently, ezetimibe has been shown to reduce not only low-density lipoprotein cholesterol but also triglyceride (TG) levels. The aim of this study was to investigate the associations of residual risk factors, mainly hypertriglyceridemia, with endothelial function during statin therapy in patients with coronary heart disease and examine the effect of ezetimibe add-on therapy. A total of 109 consecutive patients with coronary heart disease during statin therapy were enrolled. Lipid profile was measured and endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery in a fasting state. Next, 32 patients with high TG levels (≥150 mg/dl) were prospectively assigned to the ezetimibe add-on group or the no-ezetimibe group, and endothelial function was assessed after 3 months. Multivariate linear regression analysis demonstrated that serum TG and high-density lipoprotein cholesterol levels were independent determinants of percentage FMD (β = -0.210 and 0.208, respectively, p <0.05). In patients with high TG levels, ezetimibe add-on therapy significantly improved percentage FMD (from 3.3 ± 1.1% to 4.0 ± 1.1%, p <0.005), whereas no significant change was observed in the no-ezetimibe group. Moreover, the improvement in percentage FMD was significantly associated with reduction in serum TG levels (β = -0.387, p <0.05) independent of the change in serum low-density lipoprotein cholesterol levels. In conclusion, hypertriglyceridemia is independently associated with endothelial dysfunction in patients with coronary heart disease during statin therapy. Ezetimibe add-on therapy improves endothelial function in these high-risk populations.
authors.affiliation: Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Japan. kei.yunoki@gmail.com
authors.forename: Kei
authors.initials: K
authors.lastname: Yunoki
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Toru
authors.initials: T
authors.lastname: Miyoshi
authors.forename: Kenki
authors.initials: K
authors.lastname: Enko
authors.forename: Motoki
authors.initials: M
authors.lastname: Kubo
authors.forename: Masato
authors.initials: M
authors.lastname: Murakami
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hata
authors.forename: Kunihisa
authors.initials: K
authors.lastname: Kohno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morita
authors.forename: Kengo F
authors.initials: KF
authors.lastname: Kusano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001384:Azetidines / Q000009:adverse effects / Q000627:therapeutic use*; D008076:Cholesterol, HDL; D001026:Coronary Artery Bypass; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects*; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy*; D007564:Japan; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D012044:Regression Analysis; D055502:Secondary Prevention; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001384:Azetidines; D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides; D000069438:Ezetimibe