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Circulating Omega-6 Polyunsaturated Fatty Acids and Total and Cause-Specific Mortality: The Cardiovascular Health Study
Study Questions:
What are the associations between circulating n-6 polyunsaturated fatty acid (PUFA) including linoleic acid (LA) (the major dietary PUFA), γ-linolenic acid (GLA), dihomo-γ–linolenic acid (DGLA), and arachidonic acid (AA), with total and cause-specific mortality in the Cardiovascular Health Study, an elder community-based US cohort?
Methods:
Among 2,792 participants (ages ≥65 years) free of cardiovascular disease (CVD) at baseline, plasma phospholipid n-6 PUFA was measured at baseline using standardized methods. All-cause and cause-specific mortality, and total incident coronary heart disease (CHD) and stroke, were assessed and adjudicated centrally. Associations of PUFA with risk were assessed by Cox regression.
Results:
At baseline, mean age was 74 years and 64% were women. During 34,291 person-years of follow-up (1992-2010), 1,994 deaths occurred (678 CV deaths), with 427 fatal and 418 nonfatal CHD, and 154 fatal and 399 nonfatal strokes. Circulating LA showed the greatest dose-response association with intake of LA up to approximately 8% of total daily energy; with relatively smaller increases at intakes >8%. In multivariable models, higher LA was associated with lower total mortality, with extreme-quintile hazard ratio (HR) = 0.87 (p trend = 0.005). Lower death was largely attributable to CVD causes, especially nonarrhythmic CHD mortality (HR, 0.51; 95% confidence interval [CI], 0.32-0.82; p-trend = 0.001). Circulating GLA, DGLA, and AA were not significantly associated with total or cause-specific mortality (e.g., for AA and CHD death). LA showed graded inverse associations with total mortality (p = 0.005). When subjects were stratified based on their joint LA and n-3 PUFA concentrations, those with the highest circulating levels of both LA and n-3 PUFA had 54% lower risk of total mortality and 64% lower risk of CVD mortality relative to those with lowest levels of both.
Conclusions:
The authors concluded that high circulating LA, but not other n-6 PUFA, was inversely associated with total and CHD mortality in older adults.
Perspective:
The adjusted 11% reduction in total mortality and 49% lower risk across quintiles among CVD subtypes is impressive. But recommending up to 8% of total calorie intake as LA leaves very little for the other major PUFA, the omega-3 fatty acids. The findings should not be used to justify increasing the PUFAs for CVD risk reduction. The ratio of n-6 to n-3 PUFAs (most common fish products) is important. In this study, subjects in the highest quartile of n-3 PUFA and lowest quartile of n-6 PUFA still had a significant reduction in CVD mortality, while those in the highest quartile of n-6 PUFA had no significant benefit but for those in the highest quartile of n-3 PUFA (see data supplement Figure 2).
Keywords: Stroke, Follow-Up Studies, Fatty Acids, Omega-3, Risk Reduction Behavior, Coronary Disease, Risk Factors, Confidence Intervals
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