title: Circulating omega-6 polyunsaturated fatty acids and total and cause-specific mortality: the Cardiovascular Health Study.
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.
  
  
  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.
authors.affiliation: From The George Institute for Global Health, Sydney Medical School, The University of Sydney, New South Wales, Australia (J.H.Y.W.); Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle (R.N.L., B.M.P.); the Department of Internal Medicine, University of New Mexico, Albuquerque (I.B.K.); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (X.S.); the Department of Epidemiology and Health Service, University of Washington, Seattle (B.M.P.); Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.); New York Academy of Medicine, New York (D.S.S.); and Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (D.M.). jwu1@georgeinstitute.org.au.
authors.forename: Jason H Y
authors.initials: JH
authors.lastname: Wu
authors.affiliation: From The George Institute for Global Health, Sydney Medical School, The University of Sydney, New South Wales, Australia (J.H.Y.W.); Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle (R.N.L., B.M.P.); the Department of Internal Medicine, University of New Mexico, Albuquerque (I.B.K.); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (X.S.); the Department of Epidemiology and Health Service, University of Washington, Seattle (B.M.P.); Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.); New York Academy of Medicine, New York (D.S.S.); and Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (D.M.).
authors.forename: Rozenn N
authors.initials: RN
authors.lastname: Lemaitre
authors.affiliation: From The George Institute for Global Health, Sydney Medical School, The University of Sydney, New South Wales, Australia (J.H.Y.W.); Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle (R.N.L., B.M.P.); the Department of Internal Medicine, University of New Mexico, Albuquerque (I.B.K.); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (X.S.); the Department of Epidemiology and Health Service, University of Washington, Seattle (B.M.P.); Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.); New York Academy of Medicine, New York (D.S.S.); and Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (D.M.).
authors.forename: Irena B
authors.initials: IB
authors.lastname: King
authors.affiliation: From The George Institute for Global Health, Sydney Medical School, The University of Sydney, New South Wales, Australia (J.H.Y.W.); Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle (R.N.L., B.M.P.); the Department of Internal Medicine, University of New Mexico, Albuquerque (I.B.K.); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (X.S.); the Department of Epidemiology and Health Service, University of Washington, Seattle (B.M.P.); Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.); New York Academy of Medicine, New York (D.S.S.); and Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (D.M.).
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Song
authors.affiliation: From The George Institute for Global Health, Sydney Medical School, The University of Sydney, New South Wales, Australia (J.H.Y.W.); Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle (R.N.L., B.M.P.); the Department of Internal Medicine, University of New Mexico, Albuquerque (I.B.K.); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (X.S.); the Department of Epidemiology and Health Service, University of Washington, Seattle (B.M.P.); Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.); New York Academy of Medicine, New York (D.S.S.); and Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (D.M.).
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.affiliation: From The George Institute for Global Health, Sydney Medical School, The University of Sydney, New South Wales, Australia (J.H.Y.W.); Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle (R.N.L., B.M.P.); the Department of Internal Medicine, University of New Mexico, Albuquerque (I.B.K.); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (X.S.); the Department of Epidemiology and Health Service, University of Washington, Seattle (B.M.P.); Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.); New York Academy of Medicine, New York (D.S.S.); and Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (D.M.).
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.affiliation: From The George Institute for Global Health, Sydney Medical School, The University of Sydney, New South Wales, Australia (J.H.Y.W.); Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle (R.N.L., B.M.P.); the Department of Internal Medicine, University of New Mexico, Albuquerque (I.B.K.); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (X.S.); the Department of Epidemiology and Health Service, University of Washington, Seattle (B.M.P.); Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.); New York Academy of Medicine, New York (D.S.S.); and Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (D.M.).
authors.forename: Dariush
authors.initials: D
authors.lastname: Mozaffarian
mesh_terms: D000368:Aged; D016718:Arachidonic Acid / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood* / Q000401:mortality*; D015525:Fatty Acids, Omega-3 / Q000097:blood; D043371:Fatty Acids, Omega-6 / Q000097:blood*; D005231:Fatty Acids, Unsaturated / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019787:Linoleic Acid / Q000097:blood; D008297:Male; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors; D020521:Stroke / Q000097:blood* / Q000401:mortality*; D015996:Survival Rate; D014481:United States
chemical_list: D015415:Biomarkers; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D016718:Arachidonic Acid; D019787:Linoleic Acid
keywords: cardiovascular diseases; epidemiology; fatty acids, omega-6; mortality