Apolipoprotein E alleles, dyslipidemia, and coronary heart disease. The Framingham Offspring Study

Objective. —To describe the association between apolipoprotein E alleles (ε2, ε3, and ε4), 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 ε3allele, the ε4allele was associated with elevated low-density lipoprotein cholesterol values (≥4.14 mmol/L 160 mg/dL) in women, the ε2and ε4alleles were associated with moderately elevated triglyceride values (≥2.82 mmol/L 250 mg/dL) in men, and the ε2 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 ε4allele frequency was reduced in women after 60 years of age. The age-adjusted prevalence of CHD was associated with the ε4allele 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 ε4allele appears to be greater than that for any other known genetic lipid abnormality, and the association of the ε4allele with CHD remains significant in women and both sexes combined after adjustment by traditional coronary risk factors and lipids. (JAMA. 1994;272:1666-1671)