Abstract
BACKGROUND: Dysbetalipoproteinemia (DBL) is a disorder of remnant cholesterol metabolism associated with a severe risk of atherosclerotic cardiovascular disease (ASCVD).
OBJECTIVE: The objective of this study was to investigate the univariate and multivariate predictors of ASCVD in individuals with DBL.
METHODS: 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).
RESULTS: 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).
CONCLUSION: 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.