Coronary Flow Velocity Reserve is Improved by PPAR-α Agonist Fenofibrate in Patients with Hypertriglyceridemia

Authors

  • Guang Wang,

    1. Department of Endocrinology, Peking University Third Hospital, Beijing, China
    2. Department of Cardiology, Peking University Third Hospital and Key Laboratory of Cardiovascular Molecular Biology and Regulatory peptides, Ministry of Health (Peking University Third Hospital), Beijing, China
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    • Equal contributors

  • Liyun He,

    1. Department of Cardiology, Peking University Third Hospital and Key Laboratory of Cardiovascular Molecular Biology and Regulatory peptides, Ministry of Health (Peking University Third Hospital), Beijing, China
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    • Equal contributors

  • Jinbo Liu,

    1. Department of Endocrinology, Peking University Third Hospital, Beijing, China
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  • Jie Yu,

    1. Department of Cardiology, Peking University Third Hospital and Key Laboratory of Cardiovascular Molecular Biology and Regulatory peptides, Ministry of Health (Peking University Third Hospital), Beijing, China
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  • Xinheng Feng,

    1. Department of Cardiology, Peking University Third Hospital and Key Laboratory of Cardiovascular Molecular Biology and Regulatory peptides, Ministry of Health (Peking University Third Hospital), Beijing, China
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  • Fuwang Li,

    1. Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing, China
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  • Yanting Hao,

    1. Department of Cardiology, Peking University Third Hospital and Key Laboratory of Cardiovascular Molecular Biology and Regulatory peptides, Ministry of Health (Peking University Third Hospital), Beijing, China
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  • Jieming Mao,

    1. Department of Cardiology, Peking University Third Hospital and Key Laboratory of Cardiovascular Molecular Biology and Regulatory peptides, Ministry of Health (Peking University Third Hospital), Beijing, China
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  • Tianpei Hong,

    1. Department of Endocrinology, Peking University Third Hospital, Beijing, China
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  • Alex F. Chen,

    1. Department of Surgery, University of Pittsburgh School of Medicine and Vascular Surgery Research, Pittsburgh, PA, USA
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  • Xian Wang

    1. Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing, China
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Xian Wang, Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. Tel.: +8610-82801443; Fax: +8610-82801443; E-mail: xwang@bjmu.edu.cn

Abstract

Summary  Introduction: Fenofibrate, an agonist of peroxisome proliferator-activated receptor-α (PPAR-α), has a vascular protective effect. Aims: We investigated the effect of the PPAR-α agonist on coronary artery endothelial function in patients with hypertriglyceridemia. Methods: Fifty-eight patients with hypertriglyceridemia were divided into two groups: control (no treatment; n = 23) and fenofibrate treatment (n = 35), 200 mg/d, for 6 months. The patients had undergone rest and adenosine treatment to induce hyperemia for quantification of coronary flow velocity reserve (CFVR) by noninvasive Doppler echocardiography before treatment and at 6-month follow-up. Pulse wave velocity (PWV) was measured before treatment and at 6-month follow-up. Results: CFVR was significantly improved with fenofibrate treatment as compared with baseline level and control group (3.14 ± 0.36 vs. 2.80 ± 0.58 and 2.79 ± 0.65, P < 0.01 and 0.05, respectively), with no difference between baseline levels and untreated controls. In addition, at 6 months, plasma level of homocysteine was significantly increased with fenofibrate treatment as compared with at baseline and control group (median 18.13 [range 14.46–22.02]μmol/L vs. 14.09 [12.01–18.81] and 13.34 [9.69–17.06]μmol/L, P < 0.001 and 0.01, respectively). Furthermore, at 6 months, PWV was significantly decreased with fenofibrate treatment as compared with control group (1446 ± 136 cm/s vs. 1570 ± 203 cm/s, P < 0.05). Conclusions: Treatment with PPAR-α agonist fenofibrate significantly improved CFVR and arterial stiffness in patients with hypertriglyceridemia. This endothelial protective effect may be reduced in part by the side effect of increasing homocysteine.

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