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

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 HibiYoshihisa Nakagawa, Ichiro Sakuma, Yukio Ozaki, Hiroshi Iwata, Satoshi Iimuro, Hiroyuki Daida, Hiroaki Shimokawa, Takeshi Kimura, Masunori Matsuzaki, Yasushi Saito, Yutaka Matsuyama, Ryozo Nagai, Yuichi Oike

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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 cardiovascular events compared with the low-dose group in the REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease] study. In the highest quartiles, relative increases in ANGPTL8 levels were significantly associated with increased risk for secondary cardiovascular events, after adjustment for several cardiovascular disease risk factors and pitavastatin treatment (hazard ratio in Q4, 1.67 [95% CI, 1.17-2.39). Subgroup analyses showed relatively strong relationships between relative ANGPTL8 increases and secondary cardiovascular events in the high-dose pitavastatin group (hazard ratio in Q4, 2.07 [95% CI, 1.21-3.55]) and in the low ANGPTL8 group at baseline (166 <pmol/L, hazard ratio in Q4: 1.74, [95% CI, 1.04-2.93]). CONCLUSIONS: Monitoring ANGPTL8 levels over time might be useful to assess residual risk of cardiovascular secondary events in patients with cardiovascular disease undergoing statin therapy.

Original languageEnglish
Pages (from-to)1549-1559
Number of pages11
JournalArteriosclerosis, thrombosis, and vascular biology
Volume43
Issue number8
DOIs
Publication statusPublished - 01-08-2023

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Fingerprint

Dive into the research topics of 'Plasma ANGPTL8 Levels and Risk for Secondary Cardiovascular Events in Japanese Patients With Stable Coronary Artery Disease Receiving Statin Therapy'. Together they form a unique fingerprint.

Cite this