Clinical investigations
Apolipoprotein E ϵ4 allele is associated with left ventricular systolic dysfunction

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Abstract

Background

Apolipoprotein (APOE) ϵ4 allele has been associated with cardiac dysfunction in Alzheimer's 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 ϵ3/ϵ3 genotype served as a reference category.

Results

In participants who were homozygous for the ϵ4 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 ϵ3/ϵ4 was not significantly increased (OR, 1.5; 95% CI, 0.9–2.5). There was a significant allele-effect relationship for the ϵ4 allele (P-trend <.05). These elevated odds remained after adjustment for cholesterol levels and atherosclerosis parameters. Risks associated with APOE ϵ4/ϵ4 and APOE ϵ3/ϵ4 were more pronounced in participants aged ≥65 years.

Conclusion

The APOE ϵ4 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.

Section snippets

Setting and study population

The Rotterdam Study is a population-based prospective cohort study of cardiovascular, locomotor, neurologic, and ophthalmologic diseases in elderly people.8 Participants were recruited from inhabitants of Ommoord, a suburb of Rotterdam in the Netherlands, who were ≥55 years. Of the 10,275 eligible subjects, 7983 gave informed consent (78%). Participants were visited at home for a standardized questionnaire and were subsequently examined at the research center, where echocardiography was

Results

General characteristics of the study population are presented in Table I. Participants with left ventricular systolic dysfunction were on average older, more often men, and had a higher mean carotid intima-media thickness than control subjects with healthy cardiac function. Aorta calcifications and a history of myocardial infarction, CABG, or PTCA were also more frequent in case participants than in control subjects, and the percentage of former smokers was higher in the participant group. The

Discussion

The results of this study indicate that the APOE ϵ4 allele is associated with left ventricular systolic dysfunction in an elderly population. Participants homozygous for the ϵ4 allele carried 3-fold increased odds of impaired systolic function, whereas the odds of persons with APOE ϵ3/ϵ4 was nonsignificantly increased by 50%. There was a significant allele-effect relationship. The elevated risk remained after adjustment for total and HDL cholesterol levels, atherosclerosis parameters, and

Acknowledgements

We thank Christine van Broeckhoven and Marc Cruts for their efforts in APOE typing.

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    Supported by the Dutch Inspectorate for Health Care.

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