Abstract Body (Do not enter title and authors here): Background: Angiopoietin-like protein 3 (ANGPTL3) has garnered attention as a target for managing clinical lipid profiles. However, the determinants of blood ANGPTL3 levels and their prognostic significance in cardiovascular disease (CVD) remain unclear.
Aims: This study aimed to investigate the clinical determinants and prognostic significance of serum ANGPTL3 levels in patients with CVD.
Methods: A total of 311 patients with CVD (mean age 71 years, 61% male, mean body mass index 24 kg/m², 42% diabetic, median estimated glomerular filtration rate (eGFR) 57 mL/min/1.73 m², 152 patients with ischemic heart disease, 75 with valvular heart disease, 30 with cardiomyopathy, 54 with other CVD) were enrolled. Serum ANGPTL3 levels were measured using an enzyme-linked immunosorbent assay (R & D Systems) and analyzed for associations with clinical characteristics and the incidence of major adverse cardiovascular events (MACE), including all-cause mortality, non-fatal myocardial infarction, heart failure hospitalization, and ischemic stroke during a one-year follow-up.
Results: Serum ANGPTL3 levels were significantly higher in females than in males (92 [78-112] vs. 74 [56-94] ng/mL, p < 0.0001). These levels showed positive correlations with age and the levels of CRP and BNP, while negative correlations were observed with eGFR, total bilirubin (T-bil), alanine aminotransferase (ALT), albumin (Alb), hemoglobin (Hb), and platelet counts. No association was found with lipid profiles or specific CVD etiologies. Multivariate analysis identified gender, CRP, eGFR, ALT, and Hb levels as independent determinants of serum ANGPTL3 levels. During the follow-up period, 30 patients developed cardiovascular events, and receiver operating characteristic curve analysis identified a serum ANGPTL3 cutoff of 90.7 ng/mL for optimal event discrimination. Kaplan-Meier analysis showed a significantly higher incidence of MACE in patients with ANGPTL3 levels above the cutoff than those below (log-rank test, p = 0.0013). Multivariate Cox regression analysis identified elevated ANGPTL3 level as an independent determinant of MACE (hazard ratio: 1.01; 95% confidence interval: 1.00-1.02; p = 0.018).
Conclusions: In patients with CVD, serum ANGPTL3 levels, determined by gender, inflammation, liver and renal function, and anemia, can discriminate populations at high risk of developing future cardiovascular events.