Association of circulating ANGPTL3 level with all-cause and cardiovascular mortality

Abstract

Angiopoietin-like protein 3 (ANGPTL3) is a liver-derived regulator of triglyceride and cholesterol metabolism and has emerged as a notable therapeutic target for dyslipidemia [1]. However, population-level evidence linking ANGPTL3 level to mortality outcomes remains limited. Using data from UK Biobank [2], we evaluated the association of ANGPTL3 levels with all-cause and cardiovascular disease (CVD) mortality. This cohort study used UK Biobank data, which enrolled 502,007 adults aged 40-70 years from 2006 to 2010. Circulating ANGPTL3 levels were quantified using high-throughput liquid chromatography – tandem mass spectrometry (LC – MS/MS) and expressed as normalized protein expression (NPX) values, which represent relative log2-transformed protein abundances after normalization. Standard enzymatic methods were applied to determine lipid parameters, including low-density li-poprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol, triglycerides, and lipoprotein(a). To reduce disease-and treatment-related confounding, we excluded patients with baseline CVDs (ICD-10 codes with “ I01-I99 ” ), or receiving lipid-lowering therapy [3], or individuals with missing ANGPTL3 measurements/covariate data. Use of lipid-lowering therapy was determined from treatment codes for statins (atorvastatin, rosuvastatin, simvastatin, fluvastatin, pravastatin