Clinical Determinants and Prognostic Significance of Circulating Angiopoietin-Like Protein 3 Levels in Patients With Chronic Coronary Syndrome

Background: Although angiopoietin-like protein 3 (ANGPTL3) has emerged as a novel therapeutic target for lipid modulation, its prognostic significance in chronic coronary syndrome (CCS) remains unclear. This study aimed to evaluate the clinical determinants and prognostic value of circulating ANGPTL3 levels in patients with CCS. Methods and Results: We prospectively enrolled 264 consecutive patients with CCS (median age 74 years; 73% male) undergoing cardiac catheterization. Serum ANGPTL3 levels were measured using an enzyme-linked immunosorbent assay. The primary endpoint was major adverse cardiovascular events (MACE). Female sex, elevated C-reactive protein and B-type natriuretic peptide, low high-density lipoprotein cholesterol levels, and absence of statin use were independently associated with higher ANGPTL3 levels. During follow up, 35 patients experienced MACE. In multivariable Cox regression models, ANGPTL3 remained an independent predictor of MACE. Receiver operating characteristic analysis identified 90.7 ng/mL as the optimal cut-off value for event discrimination. Kaplan-Meier curves demonstrated significantly higher event rates among patients with ANGPTL3 >90.7 ng/mL. In patients with CCS with low-density lipoprotein cholesterol (LDL-C) <70 mg/dL, elevated ANGPTL3 levels were also associated with increased MACE risk. Conclusions: Circulating ANGPTL3 levels independently predict adverse cardiovascular outcomes in CCS, including those in patients who achieve LDL-C targets, and may help identify residual cardiovascular risk not captured by traditional lipid parameters.