Apolipoprotein E genotypes are associated with lipid levels and CRP but not outcomes in heart failure

Abstract

Purpose: Variations in the APOE gene has been consistently associated with lipid levels, coronary artery disease (CAD) and cognitive decline. APOE is also considered a frailty gene with average mortality risk throughout adulthood lower in epsilon2 and higher in epsilon4 carriers. But invoking a common pathway to explain the pleiotropic effects of APOE has been difficult. It is likely that the APOE associations may influenced by comorbidities and pharmacotherapy. (GP.) Methods: We tested the association of APOE genotypes on lipid levels, hsCRP and cardiovascular outcomes in 3276 elderly patients with heart failure who participated in the CORONA trial. APOE genotypes were inferred from rs429358 and rs7412 polymorphisms. The reference genotype was epsilon3/epsilon3. Adjustment for centre did not influence the results significantly. Results: The frequency of epsilon2,epsilon3, epsilon4 were 8%,81% and 12% respectively. epsilon4 carriers had significantly lower BMI, hsCRP and higher total cholesterol and LDL cholesterol (figure). Compared with epsilon3/epsilon3, the variant APOE genotypes showed no significant excess risk for the all-cause and cardiovascular events. Conclusions: In elderly patients with heart failure APOE genotype distribution showed no survivor bias. The association of high risk CRP and lipid profiles to low risk APOE genotypes in heart failure patients may partly explain the absence of relationship to outcomes.