Abstract

Background: While omega-6 polyunsaturated fatty acids (n-6 PUFA) have been recommended to reduce CHD, controversy remains about benefits vs. harms, including depending on types of n-6 PUFA and diseases examined. Aims: To assess associations of circulating n-6 PUFA including linoleic acid (LA, the major dietary PUFA), Γ-linoleic acid (GLA), dihomo-Γ-linoleic acid (DGLA), and arachidonic acid (AA),with incident total and cause-specific mortality in the Cardiovascular Health Study (CHS), a community-based US cohort. Methods: Among 2,692 participants age≥65y and free of CVD at baseline, plasma phospholipid n-6 PUFA were measured at baseline using standardized methods. All-cause and cause-specific mortality, and total (fatal or nonfatal) incident CHD and stroke, were assessed and adjudicated centrally. Associations of PUFA biomarkers with risk were assessed by multivariable Cox regression. Results: During 33,091 person-years of follow-up (1992-2010), 1920 deaths occurred (including 660 cardiovascular deaths), as well as 414 fatal and 410 nonfatal CHD events, and 150 fatal and 384 nonfatal strokes. In multivariable models, higher LA was associated with lower risk of total mortality, with extreme quintile HR 0.84 (95% CI 0.71-0.98, P- trend 0.002). Lower death was largely attributable to CVD rather than non-CVD causes, especially nonarhythmic CHD mortality (HR 0.50, 95% CI 0.31-0.80, P- trend 0.001). Phospholipid GLA, DGLA, and AA levels were not associated with total or cause-specific mortality; e.g., for AA and CHD death, the extreme quintile HR was 0.98 (95% CI 0.71-1.37, P- trend 0.72). Evaluated semi-parametrically, LA showed graded (monotonic) inverse associations with total mortality ( Figure 1A ). There was little evidence that associations of n-6 PUFA with total mortality varied by age, sex, race, or plasma n-3 PUFA (Bonferroni corrected P =NS, Figure 1B ). Conclusion: Higher circulating LA, but not other n-6 PUFA, is inversely associated with total and CHD mortality in older adults.

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