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The Framingham Offspring Study

Peter W. F. Wilson, MD; Richard H. Myers, PhD; Martin G. Larson, ScD; Jose M. Ordovas, PhD; Philip A. Wolf, MD; Ernst J. Schaefer, MD

JAMA. 1994;272(21):1666-1671.

Abstract
Objective.
—To describe the association between apolipoprotein E alleles (2, 3, and 4), dyslipidemias, and coronary heart disease (CHD).

Design.
—Cross-sectional prevalence study.

Setting and Participants.
—Community-based sample of men (n=1034) and women (n=916) aged 40 to 77 years who are participating in a long-term study of cardiovascular disease. Study participants underwent fasting lipid measurements, coronary risk factor determinations, and a comprehensive evaluation for the presence of current or previous CHD.

Results.
—Compared with the 3 allele, the 4 allele was associated with elevated low-density lipoprotein cholesterol values (4.14 mmol/L [160 mg/dL]) in women, the 2 and 4 alleles were associated with moderately elevated triglyceride values (2.82 mmol/L [250 mg/dL]) in men, and the 2 allele was associated with severely elevated triglyceride values (5.64 mmol/L [500 mg/dL]) in men. The apolipoprotein E alleles were not associated with hypertension, obesity, smoking, or diabetes, but the 4 allele frequency was reduced in women after 60 years of age. The age-adjusted prevalence of CHD was associated with the 4 allele in both men (relative odds=1.53, P=.04) and women (relative odds=1.99, P=.05). In analyses for women and for both sexes combined, this relation persisted after adjustment by hypertension, smoking, obesity, diabetes, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol.

Conclusions.
—Apolipoprotein E alleles are important genetic markers for dyslipidemia and CHD. The estimated CHD odds associated with the 4 allele appears to be greater than that for any other known genetic lipid abnormality, and the association of the 4 allele with CHD remains significant in women and both sexes combined after adjustment by traditional coronary risk factors and lipids.

(JAMA. 1994;272:1666-1671)

Author Affiliations
From the Framingham (Mass) Heart Study (Drs Wilson and Larson); Boston (Mass) University Medical Center (Drs Myers and Wolf); and the US Department of Agriculture Human Nutrition Center on Aging, Tufts University, Boston, Mass (Drs Ordovas and Schaefer).

Footnotes
Reprint requests to Framingham Heart Study, 5 Thurber St, Framingham, MA 01701 (Dr Wilson).

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