Key Findings:
In this study, associations of n-6 and n-3 PUFA, measured in plasma cholesteryl esters were assessed for the risk of fatal CHD in a prospective case-control study of Dutch adults, adjusted for confounders. A meta-analysis of nested case-control and cohort studies on plasma PUFA measured in cholesteryl esters in relation to CHD was determined. Arachidonic acid and the n-3 PUFA alpha-linolenic acid, EPA, and DHA were not associated with CHD risk in the meta-analysis. A limitation was that blood samples were stored for 18–23 years and 12–17 years for which may have affected the quality of plasma fatty acids. Further, the findings showed a small inverse association between linoleic acid in plasma cholesteryl esters and CHD risk. For plasma cholesteryl ester levels of n-3 PUFA, however, no relations with CHD risk were found in our prospective study and meta-analysis, which sheds doubt on the validity of these biomarkers of intake for epidemiological studies.
ABSTRACT:
Background: Dietary polyunsaturated fatty acids (PUFA) are inversely related to coronary heart disease (CHD) in epidemiological studies. We examined the associations of plasma n-6 and n-3 PUFA in cholesteryl esters with fatal CHD in a nested case-control study. Additionally, we performed a dose-response meta-analysis of similar prospective studies on cholesteryl ester PUFA. Methods: We used data from two population-based cohort studies in Dutch adults aged 20–65y. Blood and data collection took place from 1987–1997 and subjects were followed for 8–19y. We identified 279 incident cases of fatal CHD and randomly selected 279 controls, matched on age, gender, and enrollment date. Odds ratios (OR) were calculated per standard deviation (SD) increase of cholesteryl ester PUFA. Results: After adjustment for confounders, the OR (95%CI) for fatal CHD per SD increase in plasma linoleic acid was 0.89 (0.74–1.06). Additional adjustment for plasma total cholesterol and systolic blood pressure attenuated this association (OR:0.95; 95%CI: 0.78–1.15). Arachidonic acid was not associated with fatal CHD (OR per SD:1.11; 95%CI: 0.92–1.35). The ORs (95%CI) for fatal CHD for an SD increase in n-3 PUFA were 0.92 (0.74–1.15) for alpha-linolenic acid and 1.06 (0.88–1.27) for EPA-DHA. In the meta-analysis, a 5% higher linoleic acid level was associated with a 9% lower risk (relative risk: 0.91; 95% CI: 0.84–0.98) of CHD. The other fatty acids were not associated with CHD.
Conclusion: In this Dutch population, n-6 and n-3 PUFA in cholesteryl esters were not significantly related to fatal CHD. Our data, together with findings from previous prospective studies, support that linoleic acid in plasma cholesteryl is inversely associated with CHD. (Authors abstract)
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