Background and Purpose- The role of
dietary fat on cardiovascular health and mortality remains under debate. Because the
APOE is central to the transport and metabolism of
lipids, we examined associations between plasma
fatty acids and the risk of
stroke,
coronary heart disease, and mortality by APOE-ε4 genotype. Methods- We included 943 FHS (Framingham Heart Study) and 1406 3C (Three-City) Bordeaux Study participants. Plasma docosahexaenoic, linoleic, arachidonic, and palmitic
fatty acids were measured at baseline by gas chromatography. All-cause
stroke, ischemic stroke,
coronary heart disease, and all-cause mortality events were identified prospectively using standardized protocols. Each cohort used Cox models to separately relate
fatty acid levels to the risk of developing each event during ≤10 years of follow-up adjusting for potential confounders and stratifying by
APOE genotype (ε4 carriers versus noncarriers). We then meta-analyzed summary statistics using random-effects models. Results- On average, participants had a mean age of 74 years, 61% were women, and 21% (n=483) were APOE-ε4 carriers. Meta-analysis results showed that, only among APOE-ε4 carriers, every SD unit increase in
linoleic acid was associated with a reduced risk of all-cause
stroke (hazard ratio [HR], 0.54 [95% CI, 0.38-0.78]),
ischemic stroke (HR, 0.48 [95% CI, 0.33-0.71]), and all-cause mortality (HR, 0.70 [95% CI, 0.57-0.85]). In contrast, every SD unit increase in
palmitic acid was related to an increased risk of all-cause
stroke (HR, 1.58 [95% CI, 1.16-2.17]),
ischemic stroke (HR, 1.76 [95% CI, 1.26-2.45]), and
coronary heart disease (HR, 1.48 [95% CI, 1.09-2.01]), also in APOE-ε4 carriers only. Results for
docosahexaenoic acid and
arachidonic acid were heterogeneous between cohorts. Conclusions- These exploratory results suggest that APOE-ε4 carriers may be more susceptible to the beneficial or adverse impact of
fatty acids on
cardiovascular disease and mortality. In this subgroup, higher
linoleic acid was protective for
stroke and mortality, whereas
palmitic acid was a risk factor for
stroke and
coronary heart disease. The mechanisms underlying these novel findings warrant further investigation.