Apolipoprotein E epsilon4 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 <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.


CONCLUSIONS
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.
Bleumink
Gysèle S
GS
Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam, The Netherlands.
van Duijn
Cornelia M
CM
Kingma
J Herre
JH
Witteman
Jacqueline C M
JC
Hofman
Albert
A
Stricker
Bruno H Ch
BH
D000367:Age Factors; D000368:Aged; D000483:Alleles; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006331:Heart Diseases / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D012307:Risk Factors; D018487:Ventricular Dysfunction, Left / Q000235:genetics*
D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E