Apolipoprotein E epsilon (Porson)4 allele is associated with left ventricular systolic dysfunction

Background Apolipoprotein (APOE) epsilon (Porson)4 allele has been associated with cardiac dysfunction in Alzheimerʹs disease and β-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 ≤25%. Multivariate logistic regression was used to calculate odds ratios (ORs). The epsilon (Porson)3/epsilon (Porson)3 genotype served as a reference category. Results In participants who were homozygous for the epsilon (Porson)4 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 epsilon (Porson)3/epsilon (Porson)4 was not significantly increased (OR, 1.5; 95% CI, 0.9–2.5). There was a significant allele-effect relationship for the epsilon (Porson)4 allele (P-trend <.05). These elevated odds remained after adjustment for cholesterol levels and atherosclerosis parameters. Risks associated with APOE epsilon (Porson)4/epsilon (Porson)4 and APOE epsilon (Porson)3/epsilon (Porson)4 were more pronounced in participants aged ≥65 years. Conclusion The APOE epsilon (Porson)4 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.