Apolipoprotein E ε4 allele is associated with left ventricular systolic dysfunction

Background Apolipoprotein (APOE) epsilon4 allele has been associated with cardiac dysfunction in Alzheimer's disease and beta-thalassemia. We investigated the association between APOE genotypes and left ventricular dysfunction in a population of community-dwelling elderly subjects. Methods This study was performed in the Rotterdam Study, a population-based prospective cohort study among elderly subjects. For 2206 participants, a baseline echocardiogram and blood specimens for APOE typing were available. Cardiac dysfunction was considered present when fractional shortening was less than or equal to25%. Multivariate logistic regression was used to calculate odds ratios (ORs). The epsilon3/epsilon3 genotype served as a reference category. Results In participants who were homozygous for the epsilon4 allele, the odds of cardiac dysfunction was increased 3-fold (OR, 3.1; 95% CI, 1.2-8.1), whereas the odds of cardiac dysfunction in persons with APOE epsilon3/epsilon4 was not significantly increased (OR, 1.5; 95% CI, 0.9-2.5). There was a significant allele-effect relationship for the epsilon4 allele (beta-trend <.05). These elevated odds remained after adjustment for cholesterol levels and atherosclerosis parameters. Risks associated with APOE epsilon4/epsilon4 and APOE epsilon3/epsilon4 were more pronounced in participants aged greater than or equal to65 years. Conclusion The APOE epsilon4 allele is an independent risk factor for cardiac dysfunction in elderly people. Besides well-known effects on atherosclerosis and cholesterol levels, there may be other mechanisms, such as apoptosis, through which this allele exerts negative effects on myocardial performance.