@article {6613, title = {Circulating omega-6 polyunsaturated fatty acids and total and cause-specific mortality: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {130}, year = {2014}, month = {2014 Oct 7}, pages = {1245-53}, 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 = {Aged, Arachidonic Acid, Biomarkers, Cohort Studies, Coronary Disease, Fatty Acids, Omega-3, Fatty Acids, Omega-6, Fatty Acids, Unsaturated, Female, Follow-Up Studies, Humans, Linoleic Acid, Male, Prospective Studies, Regression Analysis, Risk Factors, Stroke, Survival Rate, United States}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.114.011590}, author = {Wu, Jason H Y and Lemaitre, Rozenn N and King, Irena B and Song, Xiaoling and Psaty, Bruce M and Siscovick, David S and Mozaffarian, Dariush} } @article {8911, title = {Serum Non-Esterified Fatty Acids, Carotid Artery Intima-Media Thickness and Flow-Mediated Dilation in Older Adults: The Cardiovascular Health Study (CHS).}, journal = {Nutrients}, volume = {13}, year = {2021}, month = {2021 Aug 31}, abstract = {

Elevated common carotid artery intima-media thickness (carotid IMT) and diminished flow-mediated dilation (FMD) are early subclinical indicators of atherosclerosis. Serum total non-esterified fatty acid (NEFA) concentrations have been positively associated with subclinical atherosclerosis. The relations between individual NEFA, carotid IMT and FMD have as yet to be assessed. We investigated the associations between fasting serum individual NEFA, carotid IMT and FMD among Cardiovascular Health Study (CHS) participants with ( = 255 for carotid IMT, 301 for FMD) or without ( = 1314 for carotid IMT, 1462 for FMD) known atherosclerotic cardiovascular disease (ASCVD). Using archived samples (fasting) collected from 1996-1997 (baseline), 35 individual NEFAs were measured using gas chromatography. Carotid IMT and estimated plaque thickness (mean of maximum internal carotid IMT) were determined in 1998-1999. FMD was measured in 1997-1998. Linear regression adjusted by the Holm-Bonferroni method was used to assess relations between individual NEFA, carotid IMT and FMD. In multivariable adjusted linear regression models per SD increment, the non-esterified fatty acid conjugated linoleic acid (-18:2 CLA) was positively associated with carotid IMT [β (95\% CI): 44.8 (19.2, 70.4), = 0.025] among participants with, but not without, ASCVD [2.16 (-6.74, 11.5), = 1.000]. Non-esterified -palmitoleic acid (16:1n-7) was positively associated with FMD [19.7 (8.34, 31.0), = 0.024] among participants without, but not with ASCVD. No significant associations between NEFAs and estimated plaque thickness were observed. In older adults, serum non-esterified CLA and palmitoleic acid were positively associated with carotid IMT and FMD, respectively, suggesting potential modifiable biomarkers for arteriopathy.

}, keywords = {Aged, Aged, 80 and over, Atherosclerosis, Biomarkers, Brachial Artery, Carotid Artery, Common, Carotid Intima-Media Thickness, Dilatation, Fatty Acids, Monounsaturated, Fatty Acids, Nonesterified, Female, Humans, Linoleic Acid, Male, Regional Blood Flow, Risk Factors, Ultrasonography}, issn = {2072-6643}, doi = {10.3390/nu13093052}, author = {Huang, Neil K and B{\r u}zkov{\'a}, Petra and Matthan, Nirupa R and Djouss{\'e}, Luc and Kizer, Jorge R and Mukamal, Kenneth J and Polak, Joseph F and Lichtenstein, Alice H} }