Prognostic predictive value of circulating angiopoietin-like protein 3 in patients with chronic coronary syndrome

Background Angiopoietin-like protein 3 (ANGPTL3) is an emerging therapeutic target for managing lipid profiles; however, its prognostic significance in patients with chronic coronary syndrome (CCS) remains undefined. Aim To examine the prognostic predictive value of circulating ANGPTL3 levels in a cohort of patients with CCS, including those with optimally controlled low-density lipoprotein cholesterol (LDL-C). Methods We enrolled 226 patients with CCS (mean age, 74 years; male patients, 74%; mean body mass index, 24 kg/m2; diabetes, 49%; median estimated glomerular filtration rate, 57 mL/min/1.73 m2). Serum ANGPTL3 levels were quantified using an enzyme-linked immunosorbent assay (R&D Systems), and the 1-year incidence of major adverse cardiovascular events (MACEs), including all-cause mortality, nonfatal myocardial infarction, heart failure requiring hospitalization, and ischemic stroke, was examined. Results During the follow-up period, 20 (7.7%) patients developed MACEs. Multivariate Cox regression analyses across multiple different models demonstrated that serum ANGPTL3 levels independently determine the incidence of MACEs (p < 0.05 in all models). Receiver operating characteristic curve analysis revealed a serum ANGPTL3 level of 109.7 ng/mL as an optimal cutoff value for event discrimination. Kaplan-Meier analysis also showed a significantly higher incidence of MACEs in patients with ANGPTL3 levels exceeding 109.7 ng/mL than in those with lower levels (log-rank test, p = 0.0001). A similar trend was also observed in the subset of patients with LDL-C levels of ≤70 mg/dL (log-rank test, p <0.0001). Conclusion Circulating ANGPTL3 levels can serve as a prognostic marker in patients with CCS, providing effective risk stratification for CCS overall and within CCS cohorts that have achieved target LDL-C levels.