Predictors of cardiovascular disease in individuals with dysbetalipoproteinemia: a prospective study in the UK Biobank.

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 2,699 individuals with ε2/ε2 genotypes from the UK Biobank were included in this study. DBL was defined as having an ε2ε2 genotype with evidence of dyslipidemia, defined as total cholesterol ≥ 200 mg/dL [5.2 mmol/L] and TG ≥ 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 ε2/ε2 DBL group (84%) compared to the ε2/ε2 non-DBL group (94%) (p<0.0001), and for DBL individuals with a PRSCAD ≥ median (79%) compared to those with a PRSCAD < median (89%) (p=0.001).

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 ε2/ε2 carriers to identify high risk individuals that would need aggressive cardiovascular management despite their low apolipoprotein B value.