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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.

Original publication




Journal article


Am Heart J

Publication Date





685 - 689


Age Factors, Aged, Alleles, Apolipoprotein E3, Apolipoprotein E4, Apolipoproteins E, Case-Control Studies, Cohort Studies, Female, Genotype, Heart Diseases, Humans, Logistic Models, Male, Middle Aged, Multivariate Analysis, Odds Ratio, Risk Factors, Ventricular Dysfunction, Left