Apolipoprotein E epsilon4 allele is associated with left ventricular systolic dysfunction

Abstract

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 <or=25%. 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 (P-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 >or=65 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.