Predictors of Cardiovascular Disease in Individuals With Dysbetalipoproteinemia: A Prospective Study in the UK Biobank.

Abstract

Dysbetalipoproteinemia (DBL) is a disorder of remnant cholesterol metabolism associated with a severe risk of atherosclerotic cardiovascular disease (ASCVD). The objective of this study was to investigate the univariate and multivariate predictors of ASCVD in individuals with DBL. Data from 2699 individuals with ɛ2/ɛ2 genotypes from the UK Biobank were included in this study. DBL was defined as having an ɛ2ɛ2 genotype with evidence of dyslipidemia, defined as total cholesterol ≥ 200 mg/dL (5.2 mmol/L) and triglyceride ≥ 175 mg/dL (2.0 mmol/L) or lipid-lowering therapy use (n = 964). Age, hypertension, waist circumference, and a polygenic risk score for coronary artery disease (PRSCAD) were independent predictors of ASCVD among individuals with DBL. Cumulative ASCVD-free survival was lower in the ɛ2/ɛ2 DBL group (84%) compared to the ɛ2/ɛ2 non-DBL group (94%) (P < .0001) and for DBL individuals with a PRSCAD ≥ median (79%) compared to those with a PRSCAD < median (89%) (P = .001). We show in a large prospective cohort that a PRSCAD predicts the ASCVD risk among individuals with DBL. The findings of the present study highlight the need for better risk stratification in ɛ2/ɛ2 carriers to identify high-risk individuals who would need aggressive cardiovascular management despite their low apolipoprotein B value.