Plasma ANGPTL8 Levels and Risk for Secondary Cardiovascular Events in Japanese Patients With Stable Coronary Artery Disease Receiving Statin Therapy

作者：Jun Morinaga, Kosuke Kashiwabara, Daisuke Torigoe, Yusuke Okadome, Kenichi Aizawa, Kohei Uemura, Ai Kurashima, Eiji Matsunaga, Hirotaka Fukami, Haruki Horiguchi, Michio Sato, Taichi Sugizaki, Keishi Miyata, Tsuyoshi Kadomatsu, Masashi Mukoyama, Katsumi Miyauchi, Seiji Hokimoto, Yoshihiro Fukumoto, Takafumi Hiro, Kiyoshi Hibi, Yoshihisa Nakagawa, Ichiro Sakuma, Yukio Ozaki, Hiroshi Iwata, Satoshi Iimuro, Hiroyuki Daida, Hiroaki Shimokawa, Takeshi Kimura, Masunori Matsuzaki, Yasushi Saitō, Yutaka Matsuyama, Ryozo Nagai, Yuichi Oike · 发表于：Arteriosclerosis Thrombosis and Vascular Biology · 年份：2023 · DOI：10.1161/atvbaha.122.318880 · 被引用次数：10 · 研究领域：Lipid metabolism and disorders、Lipoproteins and Cardiovascular Health、Adipokines, Inflammation, and Metabolic Diseases

BACKGROUND: The ability to predict secondary cardiovascular events could improve health of patients undergoing statin treatment. Circulating ANGPTL8 (angiopoietin-like protein 8) levels, which positively correlate with proatherosclerotic lipid profiles, activate the pivotal proatherosclerotic factor ANGPTL3. Here, we assessed potential association between circulating ANGPTL8 levels and risk of secondary cardiovascular events in statin-treated patients. METHODS: We conducted a biomarker study with a case-cohort design, using samples from a 2018 randomized control trial known as randomized evaluation of high-dose (4 mg/day) or low-dose (1 mg/day) lipid-lowering therapy with pitavastatin in coronary artery disease (REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease])." From that study's full analysis set (n=12 413), we selected 2250 patients with stable coronary artery disease (582 with the primary outcome, 1745 randomly chosen, and 77 overlapping subjects). A composite end point including cardiovascular-related death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergent admission was set as a primary end point. Circulating ANGPTL8 levels were measured at baseline and 6 months after randomization. RESULTS: Over a 6-month period, ANGPTL8 level changes significantly decreased in the high-dose pitavastatin group, which showed 19% risk reduction of secondary cardiova...