APOE genotype, lipids, and coronary heart disease risk: a prospective population study.
Level 3 - non-randomized controlled study
Prospective population-based cohort study
PubMed 19667307 · doi:10.1001/archinternmed.2009.234
What was done
Researchers examined the relationship between APOE genotype (*E3/*E3, *E3/*E4, *E2/*E3, *E4/*E4, *E2/*E4, *E2/*E2) and fatal and nonfatal coronary heart disease (CHD) in 22,169 participants (10,035 men and 12,134 women, aged 40 to 79 years) from the Norfolk, England, arm of the EPIC study. Participants were followed for an average of 11 years (1993-2007) with multivariable adjustments including traditional cardiovascular risk factors and lipid ratios.
What was found
During follow-up, 2,712 CHD events occurred. Compared to homozygous *E3/*E3 individuals, age- and sex-adjusted hazard ratios were 0.88 (95% CI, 0.77-0.99) for *E2 carriers (*E2/*E2 and *E2/*E3) and 1.09 (95% CI, 1.00-1.19) for *E4 carriers (*E3/*E4 and *E4/*E4). Additional adjustment for blood pressure, BMI, diabetes, alcohol, activity, and smoking did not substantially alter findings. However, after further adjustment for baseline ratio of LDL to HDL cholesterol, the hazard ratios attenuated to 0.97 (95% CI, 0.85-1.10) for *E2 carriers and 1.06 (95% CI, 0.97-1.15) for *E4 carriers. No interactions by sex, smoking status, or age groups were observed.
Why it matters
This paper demonstrates in a large cohort that the association between APOE variants and CHD risk is primarily mediated by circulating lipid fractions rather than independent vascular pathways.
Limits
The study is an observational cohort limited to Norfolk, England, which may limit generalizability across diverse racial and ethnic groups. Risk factors and lipid profiles were assessed only at baseline without accounting for subsequent changes or interventions over the 11-year follow-up.
Cited by
- supports Once corrected for LDL particle number or ApoB, the increased risk of cardiovascular disease from APOE 4/4 or 3/4 genotypes disappears.