Circulating omega-6 polyunsaturated fatty acids and total and cause-specific mortality: the Cardiovascular Health Study - PubMed (original) (raw)

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Circulating omega-6 polyunsaturated fatty acids and total and cause-specific mortality: the Cardiovascular Health Study

Jason H Y Wu et al. Circulation. 2014.

Abstract

Background: Although omega-6 polyunsaturated fatty acids (n-6 PUFA) have been recommended to reduce coronary heart disease (CHD), controversy remains about benefits versus harms, including concerns over theorized proinflammatory effects of n-6 PUFA. We investigated associations of circulating n-6 PUFA including linoleic acid (the major dietary PUFA), γ-linolenic acid, dihomo-γ-linolenic acid, and arachidonic acid, with total and cause-specific mortality in the Cardiovascular Health Study, a community-based U.S. cohort.

Methods and results: Among 2792 participants(aged ≥65 years) free of cardiovascular disease at baseline, plasma phospholipid n-6 PUFA were measured at baseline using standardized methods. All-cause and cause-specific mortality, and total incident CHD and stroke, were assessed and adjudicated centrally. Associations of PUFA with risk were assessed by Cox regression. During 34 291 person-years of follow-up (1992-2010), 1994 deaths occurred (678 cardiovascular deaths), with 427 fatal and 418 nonfatal CHD, and 154 fatal and 399 nonfatal strokes. In multivariable models, higher linoleic acid was associated with lower total mortality, with extreme-quintile hazard ratio =0.87 (P trend=0.005). Lower death was largely attributable to cardiovascular disease causes, especially nonarrhythmic CHD mortality (hazard ratio, 0.51; 95% confidence interval, 0.32-0.82; P trend=0.001). Circulating γ-linolenic acid, dihomo-γ-linolenic acid, and arachidonic acid were not significantly associated with total or cause-specific mortality (eg, for arachidonic acid and CHD death, the extreme-quintile hazard ratio was 0.97; 95% confidence interval, 0.70-1.34; P trend=0.87). Evaluated semiparametrically, linoleic acid showed graded inverse associations with total mortality (P=0.005). There was little evidence that associations of n-6 PUFA with total mortality varied by age, sex, race, or plasma n-3 PUFA. Evaluating both n-6 and n-3 PUFA, lowest risk was evident with highest levels of both.

Conclusions: High circulating linoleic acid, but not other n-6 PUFA, was inversely associated with total and CHD mortality in older adults.

Keywords: cardiovascular diseases; epidemiology; fatty acids, omega-6; mortality.

© 2014 American Heart Association, Inc.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr. Mozaffarian reports ad hoc travel reimbursement or honoraria from Bunge, Pollock Institute, Quaker Oats, and Life Sciences Research Organization; ad hoc consulting fees from McKinsey Health Systems Institute, Foodminds, Nutrition Impact, Amarin, Omthera, and Winston and Strawn LLP; membership, Unilever North America Scientific Advisory Board; royalties from UpToDate; and research grants from GlaxoSmithKline, Sigma Tau, Pronova, the Gates Foundation, the Sackler Institute of Nutrition, and the National Institutes of Health. The other authors report no conflicts.

Figures

Figure 1

Figure 1

Relationship between estimated dietary consumption of linoleic acid and arachidonic acid and their circulating concentrations in plasma phospholipids, evaluated using restricted cubic splines and adjusted for age, gender, race, BMI, and use of lipid lowering medications. The solid lines and shaded areas represent the central risk estimates and 95% CIs, respectively. Median intakes of linoleic acid and arachidonic acid were 6% of total energy (14.1g/day) and 0.08% of total energy (0.17g/day), respectively. Strong evidence was seen for both overall positive association (P < 0.001) and nonlinearity (P < 0.001) of the relationship between dietary and circulating linoleic acid. In contrast, little evidence of either an overall relationship (P = 0.24) or nonlinearity (P = 0.40) was evident for dietary and circulating arachidonic acid.

Figure 2

Figure 2

Multivariable hazard ratios of plasma phospholipid linoleic acid with risk of total mortality, evaluated by restricted cubic splines from Cox models adjusted for age, gender, race, enrollment site, education, smoking status, prevalent diabetes, atrial fibrillation, and hypertension, leisure-time physical activity, body mass index, waist circumference, alcohol use, and plasma phospholipid long-chain n-3 PUFA levels. The solid lines and shaded areas represent the central risk estimates and 95% CIs, respectively, relative to the reference level (12.5th percentile). The dotted vertical lines correspond to the 10th, 25th, 50th, 75th, and 90th percentiles of linoleic acid levels. A significant inverse association was evident (P=0.005), with little evidence for nonlinearity (P nonlinearity=0.16).

Figure 3

Figure 3

Multivariable hazard ratios for total mortality by joint levels of plasma phospholipid linoleic acid and long-chain n-3 PUFA, adjusted for age, gender, race, enrollment site, education, smoking status, prevalent diabetes, atrial fibrillation, and hypertension, leisure-time physical activity, body mass index, waist circumference, and alcohol use, *P<0.05 compared with the referent category. Associations appeared independent, with little evidence for significant interaction between linoleic acid and long-chain n-3 PUFA (Wald test for multiplicative interaction: _P_=0.54).

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