TY - JOUR T1 - Circulating palmitoleic acid and risk of metabolic abnormalities and new-onset diabetes. JF - Am J Clin Nutr Y1 - 2010 A1 - Mozaffarian, Dariush A1 - Cao, Haiming A1 - King, Irena B A1 - Lemaitre, Rozenn N A1 - Song, Xiaoling A1 - Siscovick, David S A1 - Hotamisligil, Gökhan S KW - Aged KW - Aged, 80 and over KW - Alcohol Drinking KW - Body Mass Index KW - Cholesterol KW - Cholesterol, HDL KW - Diabetes Mellitus KW - Diet KW - Dietary Carbohydrates KW - Fatty Acids, Monounsaturated KW - Female KW - Fibrinogen KW - Humans KW - Insulin Resistance KW - Life Style KW - Lipids KW - Male KW - Proportional Hazards Models KW - Prospective Studies KW - Risk Factors KW - Sex Factors KW - Triglycerides AB -

BACKGROUND: Animal experiments suggest that circulating palmitoleic acid (cis-16:1n-7) from adipocyte de novo fatty acid synthesis may directly regulate insulin resistance and metabolic dysregulation.

OBJECTIVE: We investigated the independent determinants of circulating palmitoleate in free-living humans and whether palmitoleate is related to lower metabolic risk and the incidence of diabetes.

DESIGN: In a prospective cohort of 3630 US men and women in the Cardiovascular Health Study, plasma phospholipid fatty acids, anthropometric variables, blood lipids, inflammatory markers, and glucose and insulin concentrations were measured between 1992 and 2006 by using standardized methods. Independent determinants of plasma phospholipid palmitoleate and relations of palmitoleate with metabolic risk factors were investigated by using multivariable-adjusted linear regression. Relations with incident diabetes (296 incident cases) were investigated by using Cox proportional hazards.

RESULTS: The mean (± SD) palmitoleate value was 0.49 ± 0.20% (range: 0.11-2.55%) of total fatty acids. Greater body mass index, carbohydrate intake, protein intake, and alcohol use were each independent lifestyle correlates of higher palmitoleate concentrations. In multivariable analyses that adjusted for these factors and other potential confounders, higher palmitoleate concentrations were independently associated with lower LDL cholesterol (P < 0.001), higher HDL cholesterol (P < 0.001), lower total:HDL-cholesterol ratio (P = 0.04), and lower fibrinogen (P < 0.001). However, palmitoleate was also associated with higher triglycerides (P < 0.001) and (in men only) with greater insulin resistance (P < 0.001). Palmitoleate was not significantly associated with incident diabetes.

CONCLUSIONS: Adiposity (energy imbalance), carbohydrate consumption, and alcohol use-even within typical ranges-are associated with higher circulating palmitoleate concentrations. Circulating palmitoleate is robustly associated with multiple metabolic risk factors but in mixed directions, perhaps related to divergent lifestyle determinants or endogenous sources (liver, adipose tissue) of fatty acid synthesis.

VL - 92 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/20943795?dopt=Abstract ER - TY - JOUR T1 - Food sources of individual plasma phospholipid trans fatty acid isomers: the Cardiovascular Health Study. JF - Am J Clin Nutr Y1 - 2010 A1 - Micha, Renata A1 - King, Irena B A1 - Lemaitre, Rozenn N A1 - Rimm, Eric B A1 - Sacks, Frank A1 - Song, Xiaoling A1 - Siscovick, David S A1 - Mozaffarian, Dariush KW - Aged KW - Cardiovascular System KW - Diet KW - Diet Surveys KW - Dietary Fats KW - Female KW - Food Analysis KW - Health KW - Humans KW - Hydrogenation KW - Isomerism KW - Male KW - Phospholipids KW - Plant Oils KW - Regression Analysis KW - Surveys and Questionnaires KW - Trans Fatty Acids AB -

BACKGROUND: The overall consumption of trans fatty acids (TFAs) increases the risk of coronary artery disease. However, multiple TFA isomers exist, each with potentially different health effects. Different food sources of these specific TFA isomers are not well established.

OBJECTIVE: Our objective was to determine the major independent food sources of specific TFA isomers.

DESIGN: We investigated relations of major potential food sources of TFAs, as assessed by serial food-frequency questionnaires, with 10 plasma phospholipid TFA isomers [5 trans (t-) 18:1, 3 t-18:2, and 2 t-16:1] in 3330 older adults in the Cardiovascular Health Study, a community-based multicenter cohort. Stepwise regression was used to identify independent major food sources of individual plasma phospholipid TFA isomers, which were adjusted for demographic, lifestyle, and dietary factors.

RESULTS: All 5 t-18:1 isomers were similarly associated with foods commonly made with partially hydrogenated vegetable oils (PHVOs), including biscuits (0.51 higher SD of total 18:1 fatty acid concentrations per serving/d, P < 0.01), chips and/or popcorn (0.33 higher SD per serving/d, P = 0.02), margarine (0.32 higher SD per serving/d, P < 0.001), fried foods (0.32 higher SD per serving/d, P = 0.04), and bakery foods (0.23 higher SD per serving/d, P = 0.02). Each of the t-18:2 isomers were associated only with bakery foods (0.50 higher SD of total 18:2 fatty acid concentrations per serving/d, P < 0.001). Ruminant foods were major correlates of t-16:1n-7, including red meats (0.72 higher SD per serving/d, P < 0.001), butter (0.43 higher SD per serving/d, P < 0.001), and higher-fat dairy (0.37 higher SD per serving/d, P < 0.001). In contrast, t-16:1n-9 were derived mainly from margarine (0.31 higher SD per serving/d, P < 0.001).

CONCLUSIONS: t-18:1 Isomers are similarly derived from multiple PHVO-containing foods. In contrast, t-18:2 and t-16:1n-9 isomers are derived from more-specific types of PHVO-containing foods. Ruminant foods are major sources of t-16:1n-7. Different TFA isomers and dietary sources should be considered when investigating health effects and interventions to lower TFAs.

VL - 91 IS - 4 U1 - http://www.ncbi.nlm.nih.gov/pubmed/20219966?dopt=Abstract ER - TY - JOUR T1 - Trans-palmitoleic acid, metabolic risk factors, and new-onset diabetes in U.S. adults: a cohort study. JF - Ann Intern Med Y1 - 2010 A1 - Mozaffarian, Dariush A1 - Cao, Haiming A1 - King, Irena B A1 - Lemaitre, Rozenn N A1 - Song, Xiaoling A1 - Siscovick, David S A1 - Hotamisligil, Gökhan S KW - Adiposity KW - Aged KW - C-Reactive Protein KW - Cholesterol KW - Cholesterol, HDL KW - Dairy Products KW - Diabetes Mellitus, Type 2 KW - Fatty Acids, Monounsaturated KW - Feeding Behavior KW - Female KW - Humans KW - Incidence KW - Insulin Resistance KW - Male KW - Prospective Studies KW - Risk Factors KW - Triglycerides KW - United States AB -

BACKGROUND: Palmitoleic acid (cis-16:1n-7), which is produced by endogenous fat synthesis, has been linked to both beneficial and deleterious metabolic effects, potentially confounded by diverse determinants and tissue sources of endogenous production. Trans-palmitoleate (trans-16:1n-7) represents a distinctly exogenous source of 16:1n-7, unconfounded by endogenous synthesis or its determinants, that may be uniquely informative.

OBJECTIVE: To investigate whether circulating trans-palmitoleate is independently related to lower metabolic risk and incident type 2 diabetes.

DESIGN: Prospective cohort study from 1992 to 2006.

SETTING: Four U.S. communities.

PATIENTS: 3736 adults in the Cardiovascular Health Study.

MEASUREMENTS: Anthropometric characteristics and levels of plasma phospholipid fatty acids, blood lipids, inflammatory markers, and glucose-insulin measured at baseline in 1992 and dietary habits measured 3 years earlier. Multivariate-adjusted models were used to investigate how demographic, clinical, and lifestyle factors independently related to plasma phospholipid trans-palmitoleate; how trans-palmitoleate related to major metabolic risk factors; and how trans-palmitoleate related to new-onset diabetes (304 incident cases). Findings were validated for metabolic risk factors in an independent cohort of 327 women.

RESULTS: In multivariate analyses, whole-fat dairy consumption was most strongly associated with higher trans-palmitoleate levels. Higher trans-palmitoleate levels were associated with slightly lower adiposity and, independently, with higher high-density lipoprotein cholesterol levels (1.9% across quintiles; P = 0.040), lower triglyceride levels (-19.0%; P < 0.001), a lower total cholesterol-HDL cholesterol ratio (-4.7%; P < 0.001), lower C-reactive protein levels (-13.8%; P = 0.05), and lower insulin resistance (-16.7%, P < 0.001). Trans-palmitoleate was also associated with a substantially lower incidence of diabetes, with multivariate hazard ratios of 0.41 (95% CI, 0.27 to 0.64) and 0.38 (CI, 0.24 to 0.62) in quintiles 4 and 5 versus quintile 1 (P for trend < 0.001). Findings were independent of estimated dairy consumption or other fatty acid dairy biomarkers. Protective associations with metabolic risk factors were confirmed in the validation cohort.

LIMITATION: Results could be affected by measurement error or residual confounding.

CONCLUSION: Circulating trans-palmitoleate is associated with lower insulin resistance, presence of atherogenic dyslipidemia, and incident diabetes. Our findings may explain previously observed metabolic benefits of dairy consumption and support the need for detailed further experimental and clinical investigation.

PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.

VL - 153 IS - 12 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21173413?dopt=Abstract ER - TY - JOUR T1 - Circulating long-chain ω-3 fatty acids and incidence of congestive heart failure in older adults: the cardiovascular health study: a cohort study. JF - Ann Intern Med Y1 - 2011 A1 - Mozaffarian, Dariush A1 - Lemaitre, Rozenn N A1 - King, Irena B A1 - Song, Xiaoling A1 - Spiegelman, Donna A1 - Sacks, Frank M A1 - Rimm, Eric B A1 - Siscovick, David S KW - Aged KW - Biomarkers KW - Docosahexaenoic Acids KW - Eicosapentaenoic Acid KW - Fatty Acids, Omega-3 KW - Fatty Acids, Unsaturated KW - Feeding Behavior KW - Heart Failure KW - Humans KW - Incidence KW - Proportional Hazards Models KW - Prospective Studies KW - Risk Factors AB -

BACKGROUND: Few previous studies have evaluated associations between long-chain ω-3 fatty acids and incidence of congestive heart failure (CHF), and those that have are typically based on diet questionnaires and yield conflicting results. Circulating fatty acid concentrations provide objective biomarkers of exposure.

OBJECTIVE: To determine whether plasma phospholipid concentrations of long-chain ω-3 fatty acids, including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), were associated with incident CHF.

DESIGN: Prospective cohort study.

SETTING: 4 U.S. communities.

PATIENTS: 2735 U.S. adults without prevalent heart disease who were enrolled in the Cardiovascular Health Study from 1992 to 2006.

MEASUREMENTS: Plasma phospholipid fatty acid concentrations and other cardiovascular risk factors were measured in 1992 by using standardized methods. Relationships with incident CHF (555 cases during 26 490 person-years, adjudicated by using medical records) were assessed by using Cox proportional hazards models.

RESULTS: After multivariate adjustment, plasma phospholipid EPA concentration was inversely associated with incident CHF; risk was approximately 50% lower in the highest versus the lowest quartile (hazard ratio [HR], 0.52 [95% CI, 0.38 to 0.72]; P for trend = 0.001). In similar analyses, trends toward lower risk were seen for DPA (HR, 0.76 [CI, 0.56 to 1.04]; P for trend = 0.057) and total long-chain ω-3 fatty acids (HR, 0.70 [CI, 0.49 to 0.99]; P for trend = 0.062) but not for DHA (HR, 0.84 [CI, 0.58 to 1.21]; P for trend = 0.38). In analyses censored to the middle of follow-up (7 years) to minimize exposure misclassification over time, multivariate-adjusted HRs were 0.48 for EPA (CI, 0.32 to 0.71; P for trend = 0.005), 0.61 for DPA (CI, 0.39 to 0.95; P for trend = 0.033), 0.64 for DHA (CI, 0.40 to 1.04; P for trend = 0.057), and 0.51 for total ω-3 fatty acids (CI, 0.32 to 0.80; P for trend = 0.003).

LIMITATIONS: Temporal changes in fatty acid concentrations over time may have caused underestimation of associations. Unmeasured or imperfectly measured covariates may have caused residual confounding.

CONCLUSION: Circulating individual and total ω-3 fatty acid concentrations are associated with lower incidence of CHF in older adults.

PRIMARY FUNDING SOURCE: National Institutes of Health.

VL - 155 IS - 3 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21810709?dopt=Abstract ER - TY - JOUR T1 - Fatty acids in the de novo lipogenesis pathway and risk of coronary heart disease: the Cardiovascular Health Study. JF - Am J Clin Nutr Y1 - 2011 A1 - Wu, Jason H Y A1 - Lemaitre, Rozenn N A1 - Imamura, Fumiaki A1 - King, Irena B A1 - Song, Xiaoling A1 - Spiegelman, Donna A1 - Siscovick, David S A1 - Mozaffarian, Dariush KW - Aged KW - Aged, 80 and over KW - Cohort Studies KW - Coronary Disease KW - Death, Sudden, Cardiac KW - Diet KW - Fatty Acids KW - Female KW - Humans KW - Lipogenesis KW - Male KW - Phospholipids KW - Proportional Hazards Models KW - Prospective Studies KW - Risk Factors AB -

BACKGROUND: De novo lipogenesis (DNL) is an endogenous pathway whereby carbohydrates and proteins are converted to fatty acids. DNL could affect coronary heart disease (CHD) or sudden cardiac arrest (SCA) via generation of specific fatty acids. Whether these fatty acids are prospectively associated with SCA or other CHD events is unknown.

OBJECTIVE: The objective was to investigate the relations of 4 fatty acids in the DNL pathway-palmitic acid (16:0), palmitoleic acid (16:1n-7), 7-hexadecenoic acid (16:1n-9), and cis-vaccenic acid (18:1n-7)-with incident CHD, including fatal CHD, nonfatal myocardial infarction (NFMI), and SCA.

DESIGN: A community-based prospective study was conducted in 2890 men and women aged ≥65 y, who were free of known CHD at baseline and who were followed from 1992 to 2006. Cardiovascular disease risk factors and plasma phospholipid fatty acids were measured at baseline by using standardized methods. Incident CHD was ascertained prospectively and was centrally adjudicated by using medical records. Risk was assessed by using multivariable-adjusted Cox proportional hazards.

RESULTS: During 29,835 person-years of follow-up, 631 CHD and 71 SCA events occurred. Both 18:1n-7 and 16:1n-9 were associated with a higher risk of SCA [multivariable-adjusted hazard ratio (95% CI) for the interquintile range: 7.63 (2.58, 22.6) for 18:1n-7 and 2.30 (1.16, 4.55) for 16:1n-9] but not of total CHD, fatal CHD, or NFMI. In secondary analyses censored to mid-follow-up (7 y) to minimize the effects of changes in concentrations over time, 16:1n-9 was also associated with a significantly higher risk of total CHD (2.11; 1.76, 2.54), including a higher risk of CHD death, NFMI, and SCA; 16:0 and 16:1n-7 were not associated with clinical CHD outcomes.

CONCLUSION: Higher plasma phospholipid 18:1n-7 and 16:1n-9 concentrations were prospectively associated with an elevated risk of SCA but not of other CHD events, except in secondary analyses.

VL - 94 IS - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21697077?dopt=Abstract ER - TY - JOUR T1 - Plasma omega-3 fatty acids and incident diabetes in older adults. JF - Am J Clin Nutr Y1 - 2011 A1 - Djoussé, Luc A1 - Biggs, Mary L A1 - Lemaitre, Rozenn N A1 - King, Irena B A1 - Song, Xiaoling A1 - Ix, Joachim H A1 - Mukamal, Kenneth J A1 - Siscovick, David S A1 - Mozaffarian, Dariush KW - Aged KW - Aged, 80 and over KW - alpha-Linolenic Acid KW - Diabetes Mellitus KW - Fatty Acids, Omega-3 KW - Female KW - Humans KW - Male KW - Phospholipids KW - Proportional Hazards Models KW - Prospective Studies AB -

BACKGROUND: Although long-chain omega-3 fatty acid (n-3 FA) consumption estimated via food-frequency questionnaires has been associated with a higher incidence of diabetes, limited prospective data on diabetes risk are available that use objective biomarkers of n-3 FAs.

OBJECTIVE: We sought to examine the relation between plasma phospholipid n-3 FAs and incident diabetes.

DESIGN: We prospectively analyzed data in 3088 older men and women (mean age: 75 y) from the Cardiovascular Health Study (1992-2007). Plasma phospholipid n-3 FAs were measured by using gas chromatography, and incident diabetes was ascertained by using information on hypoglycemic agents and serum glucose. We used Cox proportional hazards models to estimate multivariable-adjusted relative risks.

RESULTS: During a median follow-up of 10.6 y, 204 new cases of diabetes occurred. In a multivariable model that controlled for age, sex, race, clinic site, body mass index, alcohol intake, smoking, physical activity, LDL cholesterol, and linoleic acid, relative risks (95% CIs) for diabetes were 1.0 (reference), 0.96 (0.65, 1.43), 1.03 (0.69, 1.54), and 0.64 (0.41, 1.01) across consecutive quartiles of phospholipid eicosapentaenoic acid and docosahexaenoic acid (P for trend = 0.05). Corresponding relative risks (95% CIs) for phospholipid α-linolenic acid (ALA) were 1.0 (reference), 0.93 (0.65, 1.34), 0.99 (0.68, 1.44), and 0.57 (0.36, 0.90) (P for trend = 0.03).

CONCLUSIONS: With the use of objective biomarkers, long-chain n-3 FAs and ALA were not associated with a higher incidence of diabetes. Individuals with the highest concentrations of both types of FAs had lower risk of diabetes.

VL - 94 IS - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21593500?dopt=Abstract ER - TY - JOUR T1 - Association of plasma phospholipid long-chain ω-3 fatty acids with incident atrial fibrillation in older adults: the cardiovascular health study. JF - Circulation Y1 - 2012 A1 - Wu, Jason H Y A1 - Lemaitre, Rozenn N A1 - King, Irena B A1 - Song, Xiaoling A1 - Sacks, Frank M A1 - Rimm, Eric B A1 - Heckbert, Susan R A1 - Siscovick, David S A1 - Mozaffarian, Dariush KW - Aged KW - Atrial Fibrillation KW - Biomarkers KW - Dietary Fats KW - Docosahexaenoic Acids KW - Eicosapentaenoic Acid KW - Fatty Acids, Omega-3 KW - Female KW - Follow-Up Studies KW - Humans KW - Incidence KW - Male KW - Proportional Hazards Models KW - Risk Factors KW - Seafood AB -

BACKGROUND: Experimental studies suggest that long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) may reduce the risk of atrial fibrillation (AF). Prior studies evaluating fish or n-3 PUFA consumption from dietary questionnaires and incident AF have been conflicting. Circulating levels of n-3 PUFAs provide an objective measurement of exposure.

METHODS AND RESULTS: Among 3326 US men and women ≥65 years of age and free of AF or heart failure at baseline, plasma phospholipid levels of eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid were measured at baseline by use of standardized methods. Incident AF (789 cases) was identified prospectively from hospital discharge records and study visit ECGs during 31 169 person-years of follow-up (1992-2006). In multivariable Cox models adjusted for other risk factors, the relative risk in the top versus lowest quartile of total n-3 PUFAs (eicosapentaenoic acid+docosapentaenoic acid+docosahexaenoic acid) levels was 0.71 (95% confidence interval, 0.57-0.89; P for trend=0.004) and of DHA levels was 0.77 (95% confidence interval, 0.62-0.96; P for trend=0.01). Eicosapentaenoic acid and docosapentaenoic acid levels were not significantly associated with incident AF. Evaluated nonparametrically, both total n-3 PUFAs and docosahexaenoic acid showed graded and linear inverse associations with incidence of AF. Adjustment for intervening events such as heart failure or myocardial infarction during follow-up did not appreciably alter results.

CONCLUSIONS: In older adults, higher circulating total long-chain n-3 PUFA and docosahexaenoic acid levels were associated with lower risk of incident AF. These results highlight the need to evaluate whether increased dietary intake of these fatty acids could be effective for the primary prevention of AF.

VL - 125 IS - 9 U1 - http://www.ncbi.nlm.nih.gov/pubmed/22282329?dopt=Abstract ER - TY - JOUR T1 - Circulating and dietary α-linolenic acid and incidence of congestive heart failure in older adults: the Cardiovascular Health Study. JF - Am J Clin Nutr Y1 - 2012 A1 - Lemaitre, Rozenn N A1 - Sitlani, Colleen A1 - Song, Xiaoling A1 - King, Irena B A1 - McKnight, Barbara A1 - Spiegelman, Donna A1 - Sacks, Frank M A1 - Djoussé, Luc A1 - Rimm, Eric B A1 - Siscovick, David S A1 - Mozaffarian, Dariush KW - Aged KW - Alcohol Drinking KW - alpha-Linolenic Acid KW - Biomarkers KW - Body Mass Index KW - Cardiovascular Diseases KW - Diet KW - Fatty Acid Desaturases KW - Female KW - Follow-Up Studies KW - Heart Failure KW - Humans KW - Incidence KW - Male KW - Polymorphism, Single Nucleotide KW - Prevalence KW - Prospective Studies KW - Risk Factors KW - Smoking KW - Surveys and Questionnaires KW - United States AB -

BACKGROUND: Few studies have evaluated the association between the n-3 fatty acid α-linolenic acid (ALA) and the incidence of congestive heart failure (CHF).

OBJECTIVE: We investigated whether plasma phospholipid concentrations and estimated dietary consumption of ALA are associated with incident CHF.

DESIGN: We used data from the Cardiovascular Health Study, a prospective cohort study of cardiovascular diseases among adults aged ≥65 y, from 4 US communities. A total of 2957 participants free of prevalent heart disease and with available fatty acid measurements were included in biomarker analyses (30,722 person-years and 686 incident CHF events). A total of 4432 participants free of prevalent heart disease were included in dietary analyses (52,609 person-years and 1072 events). We investigated the association of ALA with incident CHF by using Cox regression.

RESULTS: After adjustment for age, sex, race, education, smoking status, BMI, waist circumference, and alcohol consumption, plasma phospholipid ALA was not associated with incident CHF (HR for the highest compared with the lowest quartile: 0.97; 95% CI: 0.79, 1.21; P-trend = 0.85). Likewise, dietary ALA was not associated with incident CHF (adjusted HR for the highest compared with the lowest quartile: 0.96; 95% CI: 0.82, 1.20; P-trend = 0.97). We observed no association of biomarker or dietary ALA with nonvalvular CHF subtype. We also found little evidence of an association between ALA and CHF in subgroups based on age, sex, diabetes, fish consumption, BMI, or FADS2 genotype (rs1535).

CONCLUSION: ALA intake is not associated with incident CHF in older adults. This trial was registered at clinicaltrials.gov as NCT00005133.

VL - 96 IS - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/22743310?dopt=Abstract ER - TY - JOUR T1 - Novel circulating fatty acid patterns and risk of cardiovascular disease: the Cardiovascular Health Study. JF - Am J Clin Nutr Y1 - 2012 A1 - Imamura, Fumiaki A1 - Lemaitre, Rozenn N A1 - King, Irena B A1 - Song, Xiaoling A1 - Lichtenstein, Alice H A1 - Matthan, Nirupa R A1 - Herrington, David M A1 - Siscovick, David S A1 - Mozaffarian, Dariush KW - Aged KW - Aged, 80 and over KW - Biomarkers KW - Cardiovascular Diseases KW - Cohort Studies KW - Coronary Artery Disease KW - Disease Progression KW - Female KW - Follow-Up Studies KW - Humans KW - Incidence KW - Longitudinal Studies KW - Male KW - Middle Aged KW - Myocardial Ischemia KW - Principal Component Analysis KW - Proportional Hazards Models KW - Prospective Studies KW - Risk Factors KW - Stroke KW - Trans Fatty Acids KW - United States AB -

BACKGROUND: Complex interplays of diet and metabolism influence circulating fatty acids (FAs), possibly constituting FA patterns related to cardiovascular disease (CVD) risk.

OBJECTIVES: We aimed to derive FA patterns from circulating FAs, relate the patterns to CVD incidence, and extend the derived patterns to atherosclerosis progression in another independent cohort.

DESIGN: We used principal component analysis (PCA) to derive FA patterns from 38 plasma phospholipid FAs in 2972 older adults in the Cardiovascular Health Study (CHS). Identified patterns were evaluated for prospective associations with 14-y incidence of CVD [ischemic heart disease (IHD) or stroke]. In another independent cohort of postmenopausal women with IHD, we evaluated associations of the CHS-derived patterns with 3.2-y progression of angiographically defined coronary atherosclerosis.

RESULTS: Three distinct patterns were identified, characterized by higher proportions of trans FAs, de novo lipogenesis (DNL) FAs, and long-chain MUFAs (LCMUFAs). During 32,265 person-years, 780 incident CVD events occurred. The trans FA pattern was associated with higher CVD risk (multivariable-adjusted HR for the highest compared with the lowest quintiles = 1.58; 95% CI: 1.17, 2.12; P-trend = 0.006), primarily attributable to higher risk of stroke (HR: 2.46; 95% CI: 1.54, 3.92; P-trend = 0.005). The DNL and LCMUFA patterns were not associated with CVD incidence or with IHD or stroke (P-trend > 0.11 each). In the second cohort, the trans FA pattern, but not the other 2 patterns, was positively associated with progression of coronary atherosclerosis (P-trend < 0.05).

CONCLUSIONS: PCA appears to provide informative circulating FA patterns. A pattern driven mainly by trans FA levels related to greater CVD risk in older adults and coronary atherosclerosis progression in women with IHD.

VL - 96 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23097270?dopt=Abstract ER - TY - JOUR T1 - Associations of plasma phospholipid and dietary alpha linolenic acid with incident atrial fibrillation in older adults: the Cardiovascular Health Study. JF - J Am Heart Assoc Y1 - 2013 A1 - Fretts, Amanda M A1 - Mozaffarian, Dariush A1 - Siscovick, David S A1 - Heckbert, Susan R A1 - McKnight, Barbara A1 - King, Irena B A1 - Rimm, Eric B A1 - Psaty, Bruce M A1 - Sacks, Frank M A1 - Song, Xiaoling A1 - Spiegelman, Donna A1 - Lemaitre, Rozenn N KW - Age Factors KW - Aged KW - Aged, 80 and over KW - alpha-Linolenic Acid KW - Atrial Fibrillation KW - Biomarkers KW - Diet KW - Female KW - Humans KW - Incidence KW - Linear Models KW - Longitudinal Studies KW - Male KW - Nutritional Status KW - Phospholipids KW - Proportional Hazards Models KW - Prospective Studies KW - Risk Assessment KW - Risk Factors KW - Time Factors KW - United States AB -

BACKGROUND: Few studies have examined the relationship of α-linolenic acid (ALA 18:3n-3), an intermediate-chain essential n-3 polyunsaturated fatty acid derived from plants and vegetable oils, with incident atrial fibrillation (AF).

METHODS AND RESULTS: The study population included participants from the Cardiovascular Health Study, a community-based longitudinal cohort of adults aged 65 or older, free of prevalent coronary heart disease and atrial fibrillation. We assessed the associations of plasma phospholipid and dietary ALA with incident AF using Cox regression. The biomarker analysis comprised a total of 2899 participants, and the dietary analysis comprised 4337 participants. We found no association of plasma phospholipid ALA and incident AF. Comparing each of the second, third, and fourth quartiles to the lowest quartile, the hazard ratios for AF were 1.11 (95% CI, 0.90 to 1.37), 1.09 (95% CI, 0.88 to 1.35), and 0.92 (95% CI, 0.74 to 1.15), after adjustment for age, sex, race, clinic, education, smoking, alcohol, body mass index, waist circumference, diabetes, heart failure, stroke, treated hypertension, and physical activity (P trend=0.48). When dietary ALA was considered the exposure of interest, results were similar.

CONCLUSIONS: Results from this prospective cohort study of older adults indicate no association of plasma phospholipid or dietary ALA and incident AF.

VL - 2 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23525429?dopt=Abstract ER - TY - JOUR T1 - Long-chain monounsaturated Fatty acids and incidence of congestive heart failure in 2 prospective cohorts. JF - Circulation Y1 - 2013 A1 - Imamura, Fumiaki A1 - Lemaitre, Rozenn N A1 - King, Irena B A1 - Song, Xiaoling A1 - Steffen, Lyn M A1 - Folsom, Aaron R A1 - Siscovick, David S A1 - Mozaffarian, Dariush KW - Aged KW - Aged, 80 and over KW - Cross-Sectional Studies KW - Dietary Fats KW - Fatty Acids, Monounsaturated KW - Feeding Behavior KW - Female KW - Heart Failure KW - Humans KW - Incidence KW - Longitudinal Studies KW - Male KW - Middle Aged KW - Nutrition Surveys KW - Prospective Studies KW - Risk Factors KW - Stroke AB -

BACKGROUND: Decades-old animal experiments suggested that dietary long-chain monounsaturated fatty acids (LCMUFAs) caused cardiotoxicity, leading, for example, development of Canola oil (Canadian oil low in erucic acid) from rapeseed. However, potential cardiotoxicity in humans and contemporary dietary sources of LCMUFAs are unknown.

METHODS AND RESULTS: We prospectively investigated the associations of plasma phospholipid LCMUFAs (20:1, 22:1, and 24:1), assessed as objective biomarkers of exposure, with incidence congestive heart failure in 2 independent cohorts: 3694 older adults (mean age, 75.2±5.2 years) in the Cardiovascular Health Study (CHS; 1992-2006) and 3577 middle-aged adults (mean age, 54.1±5.8 years) in the Atherosclerosis Risk in Communities Study, Minnesota subcohort (ARIC; 1987-2008). We further examined dietary correlates of circulating LCMUFAs in CHS and ARIC and US dietary sources of LCMUFAs in the 2003-2010 National Health and Nutrition Examination Survey (NHANES). In CHS, 997 congestive heart failure events occurred during 39 238 person-years; in ARIC, 330 events congestive heart failure events occurred during 64 438 person-years. After multivariable adjustment, higher levels of 22:1 and 24:1 were positively associated with greater incident congestive heart failure in both CHS and ARIC; hazard ratios were 1.34 (95% confidence interval, 1.02-1.76) and 1.57 (95% confidence interval, 1.11-2.23) for highest versus lowest quintiles of 22:1, respectively, and 1.75 (95% confidence interval, 1.23-2.50) and 1.92 (95% confidence interval, 1.22-3.03) for 24:1, respectively (P for trend ≤0.03 each). A variety of foods were related to circulating LCMUFAs in CHS and ARIC, consistent with food sources of LCMUFAs in NHANES, including fish, poultry, meats, whole grains, and mustard.

CONCLUSIONS: Higher circulating levels of 22:1 and 24:1, with apparently diverse dietary sources, were associated with incident congestive heart failure in 2 independent cohorts, suggesting possible cardiotoxicity of LCMUFAs in humans.

VL - 127 IS - 14 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23487436?dopt=Abstract ER - TY - JOUR T1 - Plasma phospholipid long-chain ω-3 fatty acids and total and cause-specific mortality in older adults: a cohort study. JF - Ann Intern Med Y1 - 2013 A1 - Mozaffarian, Dariush A1 - Lemaitre, Rozenn N A1 - King, Irena B A1 - Song, Xiaoling A1 - Huang, Hongyan A1 - Sacks, Frank M A1 - Rimm, Eric B A1 - Wang, Molin A1 - Siscovick, David S KW - Aged KW - Biomarkers KW - Cause of Death KW - Coronary Disease KW - Diet Records KW - Docosahexaenoic Acids KW - Eicosapentaenoic Acid KW - Fatty Acids, Omega-3 KW - Fatty Acids, Unsaturated KW - Feeding Behavior KW - Female KW - Humans KW - Male KW - Prospective Studies KW - Risk Assessment KW - Stroke AB -

BACKGROUND: Long-chain ω-3 polyunsaturated fatty acids (ω3-PUFAs), including eicosapentaenoic acid (EPA) (20:5ω-3), docosapentaenoic acid (DPA) (22:5ω-3), and docosahexaenoic acid (DHA) (22:6ω-3), have been shown to reduce cardiovascular risk, but effects on cause-specific and total mortality and potential dose-responses remain controversial. Most observational studies have assessed self-reported dietary intake and most randomized trials have tested effects of adding supplements to dietary intake and evaluated secondary prevention, thus limiting inference for dietary ω3-PUFAs or primary prevention.

OBJECTIVE: To investigate associations of plasma phospholipid EPA, DPA, DHA, and total ω3-PUFA levels with total and cause-specific mortality among healthy older adults not receiving supplements.

DESIGN: Prospective cohort study.

SETTING: 4 U.S. communities.

PARTICIPANTS: 2692 U.S. adults aged 74 years (±5 years) without prevalent coronary heart disease (CHD), stroke, or heart failure at baseline.

MEASUREMENTS: Phospholipid fatty acid levels and cardiovascular risk factors were measured in 1992. Relationships with total and cause-specific mortality and incident fatal or nonfatal CHD and stroke through 2008 were assessed.

RESULTS: During 30 829 person-years, 1625 deaths (including 570 cardiovascular deaths), 359 fatal and 371 nonfatal CHD events, and 130 fatal and 276 nonfatal strokes occurred. After adjustment, higher plasma levels of ω3-PUFA biomarkers were associated with lower total mortality, with extreme-quintile hazard ratios of 0.83 for EPA (95% CI, 0.71 to 0.98; P for trend = 0.005), 0.77 for DPA (CI, 0.66 to 0.90; P for trend = 0.008), 0.80 for DHA (CI, 0.67 to 0.94; P for trend = 0.006), and 0.73 for total ω3-PUFAs (CI, 0.61 to 0.86; P for trend < 0.001). Lower risk was largely attributable to fewer cardiovascular than noncardiovascular deaths. Individuals in the highest quintile of phospholipid ω3-PUFA level lived an average of 2.22 more years (CI, 0.75 to 3.13 years) after age 65 years than did those in the lowest quintile.

LIMITATION: Temporal changes in fatty acid levels and misclassification of causes of death may have resulted in underestimated associations, and unmeasured or imperfectly measured covariates may have caused residual confounding.

CONCLUSION: Higher circulating individual and total ω3-PUFA levels are associated with lower total mortality, especially CHD death, in older adults.

PRIMARY FUNDING SOURCE: National Institutes of Health.

VL - 158 IS - 7 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23546563?dopt=Abstract ER - TY - JOUR T1 - Circulating omega-6 polyunsaturated fatty acids and total and cause-specific mortality: the Cardiovascular Health Study. JF - Circulation Y1 - 2014 A1 - Wu, Jason H Y A1 - Lemaitre, Rozenn N A1 - King, Irena B A1 - Song, Xiaoling A1 - Psaty, Bruce M A1 - Siscovick, David S A1 - Mozaffarian, Dariush KW - Aged KW - Arachidonic Acid KW - Biomarkers KW - Cohort Studies KW - Coronary Disease KW - Fatty Acids, Omega-3 KW - Fatty Acids, Omega-6 KW - Fatty Acids, Unsaturated KW - Female KW - Follow-Up Studies KW - Humans KW - Linoleic Acid KW - Male KW - Prospective Studies KW - Regression Analysis KW - Risk Factors KW - Stroke KW - Survival Rate KW - United States AB -

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.

VL - 130 IS - 15 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25124495?dopt=Abstract ER - TY - JOUR T1 - Plasma phospholipid and dietary α-linolenic acid, mortality, CHD and stroke: the Cardiovascular Health Study. JF - Br J Nutr Y1 - 2014 A1 - Fretts, Amanda M A1 - Mozaffarian, Dariush A1 - Siscovick, David S A1 - Sitlani, Colleen A1 - Psaty, Bruce M A1 - Rimm, Eric B A1 - Song, Xiaoling A1 - McKnight, Barbara A1 - Spiegelman, Donna A1 - King, Irena B A1 - Lemaitre, Rozenn N KW - Aged KW - alpha-Linolenic Acid KW - Cardiovascular Diseases KW - Cohort Studies KW - Coronary Disease KW - Diet KW - Female KW - Humans KW - Male KW - Mortality KW - Phospholipids KW - Proportional Hazards Models KW - Prospective Studies KW - Risk Factors KW - Stroke KW - United States AB -

Previous studies have suggested that long-chain n-3 fatty acids derived from seafood are associated with a lower risk of mortality, CHD and stroke. Whether α-linolenic acid (ALA, 18 : 3n-3), a plant-derived long-chain essential n-3 fatty acid, is associated with a lower risk of these outcomes is unclear. The aim of the present study was to examine the associations of plasma phospholipid and dietary ALA with the risk of mortality, CHD and stroke among older adults who participated in the Cardiovascular Health Study, a cohort study of adults aged ≥ 65 years. A total of 2709 participants were included in the plasma phospholipid ALA analysis and 2583 participants were included in the dietary ALA analysis. Cox regression was used to assess the associations of plasma phospholipid and dietary ALA with the risk of mortality, incident CHD and stroke. In minimally and multivariable-adjusted models, plasma phospholipid ALA was found to be not associated with the risk of mortality, incident CHD or stroke. After adjustment for age, sex, race, enrolment site, education, smoking status, diabetes, BMI, alcohol consumption, treated hypertension and total energy intake, higher dietary ALA intake was found to be associated with a lower risk of total and non-cardiovascular mortality; on comparing the highest quintiles of dietary ALA with the lowest quintiles, the HR for total mortality and non-cardiovascular mortality were found to be 0·73 (95 % CI 0·61, 0·88) and 0·64 (95 % CI 0·52, 0·80), respectively. Dietary ALA was found to be not associated with the risk of cardiovascular mortality, incident CHD or stroke. In conclusion, the results of the present suggest study that dietary ALA, but not plasma phospholipid ALA, is associated with a lower risk of total and non-cardiovascular mortality in older adults.

VL - 112 IS - 7 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25159901?dopt=Abstract ER - TY - JOUR T1 - Plasma phospholipid saturated fatty acids and incident atrial fibrillation: the Cardiovascular Health Study. JF - J Am Heart Assoc Y1 - 2014 A1 - Fretts, Amanda M A1 - Mozaffarian, Dariush A1 - Siscovick, David S A1 - Djoussé, Luc A1 - Heckbert, Susan R A1 - King, Irena B A1 - McKnight, Barbara A1 - Sitlani, Colleen A1 - Sacks, Frank M A1 - Song, Xiaoling A1 - Sotoodehnia, Nona A1 - Spiegelman, Donna A1 - Wallace, Erin R A1 - Lemaitre, Rozenn N KW - Aged KW - Aged, 80 and over KW - Atrial Fibrillation KW - Eicosanoic Acids KW - Fatty Acids KW - Female KW - Humans KW - Longitudinal Studies KW - Male KW - Palmitic Acid KW - Phospholipids KW - Proportional Hazards Models KW - Prospective Studies KW - Risk Factors KW - Stearic Acids KW - United States AB -

BACKGROUND: Prior studies suggest that circulating fatty acids may influence the risk of atrial fibrillation (AF), but little is known about the associations of circulating saturated fatty acids with risk of AF.

METHODS AND RESULTS: The study population included 2899 participants from the Cardiovascular Health Study, a community-based longitudinal cohort of adults aged 65 years or older in the United States who were free of prevalent coronary heart disease and AF in 1992. Cox regression was used to assess the association of all the long-chain saturated fatty acids-palmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0)-with incident AF. During a median of 11.2 years of follow-up, 707 cases of incident AF occurred. After adjustment for other AF risk factors, higher levels of circulating 16:0 were associated with a higher risk of AF (hazard ratio comparing highest and lowest quartiles: 1.48; 95% CI: 1.18, 1.86). In contrast, higher levels of circulating 18:0, 20:0, 22:0, and 24:0 were each associated with a lower risk of AF. The hazard ratios (95% CI) for AF in the top and bottom quartiles were 0.76 (95% CI: 0.61, 0.95) for 18:0; 0.78 (95% CI: 0.63, 0.97) for 20:0; 0.62 (95% CI: 0.50, 0.78) for 22:0; and 0.68 (95% CI: 0.55, 0.85) for 24:0.

CONCLUSIONS: Results from this prospective cohort study of older adults demonstrate divergent associations of circulating 16:0 versus longer-chain saturated fatty acids with incident AF, highlighting the need to investigate both determinants of these levels and potential pathways of the observed differential risk.

VL - 3 IS - 3 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24970268?dopt=Abstract ER - TY - JOUR T1 - Plasma phospholipid trans-fatty acids levels, cardiovascular diseases, and total mortality: the cardiovascular health study. JF - J Am Heart Assoc Y1 - 2014 A1 - Wang, Qianyi A1 - Imamura, Fumiaki A1 - Lemaitre, Rozenn N A1 - Rimm, Eric B A1 - Wang, Molin A1 - King, Irena B A1 - Song, Xiaoling A1 - Siscovick, David A1 - Mozaffarian, Dariush KW - Aged KW - Aged, 80 and over KW - Biomarkers KW - Cardiovascular Diseases KW - Cohort Studies KW - Dietary Fats KW - Female KW - Follow-Up Studies KW - Humans KW - Incidence KW - Male KW - Mortality KW - Phospholipids KW - Prognosis KW - Proportional Hazards Models KW - Prospective Studies KW - Trans Fatty Acids AB -

BACKGROUND: While self-reported trans-fatty acid (TFA) consumption is linked to coronary heart disease (CHD), relationships between objective biomarkers of TFA subtypes (t-16:1n9, total t-18:1, and cis/trans-(c/t-), t/c- and t/t-18:2) and cardiovascular disease (CVD) or total mortality are not well established.

METHODS AND RESULTS: We evaluated 2742 adults in the Cardiovascular Health Study, aged 74±5 years and free of prevalent CVD, with plasma phospholipid TFA measures in 1992. Incident fatal and nonfatal CHD events, CVD and non-CVD mortality, and total mortality were centrally adjudicated through 2010. Risks were assessed using Cox proportional hazards. During 31 494 person-years, 1735 total deaths and 639 total CHD events occurred. In the multivariate model including mutual adjustment for the 5 TFA subtypes, circulating t/t-18:2 was associated with higher total mortality (extreme quintile hazard ratio (HR)=1.23, 95% CI=1.04 to 1.44, P-trend=0.01), CVD mortality (HR=1.40, 95% CI=1.05 to 1.86, P-trend=0.02), and total CHD (HR=1.39, 95% CI=1.06 to 1.83, P-trend=0.01). t/c-18:2 was positively related to total mortality (HR=1.19, P-trend=0.05), total CHD (HR=1.67, P-trend=0.002), and nonfatal CHD (HR=2.06, P-trend=0.002) after mutual adjustment; these associations were insignificant without mutual adjustment. Neither t-16:1n9 nor t-18:1 was significantly associated with total mortality or CVD, nor was c/t-18:2 if we excluded early cases.

CONCLUSIONS: Among circulating TFAs, t/t-18:2 was most adversely associated with total mortality, mainly due to the increased risk of CVD. t/c-18:2 was also positively associated with total mortality and CHD, but only after adjustment for other TFAs. These results highlight the need for further investigation of dietary sources, nondietary determinants, and health effects of specific TFA subtypes, especially t-18:2 isomers.

VL - 3 IS - 4 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25164946?dopt=Abstract ER - TY - JOUR T1 - Circulating and dietary trans fatty acids and incident type 2 diabetes in older adults: the Cardiovascular Health Study. JF - Diabetes Care Y1 - 2015 A1 - Wang, Qianyi A1 - Imamura, Fumiaki A1 - Ma, Wenjie A1 - Wang, Molin A1 - Lemaitre, Rozenn N A1 - King, Irena B A1 - Song, Xiaoling A1 - Biggs, Mary L A1 - Delaney, Joseph A A1 - Mukamal, Kenneth J A1 - Djoussé, Luc A1 - Siscovick, David S A1 - Mozaffarian, Dariush KW - Aged KW - Biomarkers KW - Diabetes Mellitus, Type 2 KW - Diabetic Angiopathies KW - Dietary Fats, Unsaturated KW - Epidemiologic Methods KW - Female KW - Food Habits KW - Humans KW - Male KW - Phospholipids KW - Trans Fatty Acids AB -

OBJECTIVE: To investigate the effects of trans fatty acids (TFAs) on type 2 diabetes mellitus (DM) by specific TFA subtype or method of assessment.

RESEARCH DESIGN AND METHODS: In the Cardiovascular Health Study, plasma phospholipid trans (t)-16:1n9, t-18:1, and cis (c)/t-, t/c-, and t/t-18:2 were measured in blood drawn from 2,919 adults aged 74 ± 5 years and free of prevalent DM in 1992. Dietary TFA was estimated among 4,207 adults free of prevalent DM when dietary questionnaires were initially administered in 1989 or 1996. Incident DM was defined through 2010 by medication use or blood glucose levels. Risks were assessed by Cox proportional hazards.

RESULTS: In biomarker analyses, 287 DM cases occurred during 30,825 person-years. Both t-16:1n9 (extreme quartile hazard ratio 1.59 [95% CI 1.04-2.42], P-trend = 0.04) and t-18:1 (1.91 [1.20-3.03], P-trend = 0.01) levels were associated with higher incident DM after adjustment for de novo lipogenesis fatty acids. In dietary analyses, 407 DM cases occurred during 50,105 person-years. Incident DM was positively associated with consumption of total TFAs (1.38 [1.03-1.86], P-trend = 0.02), t-18:1 (1.32 [1.00-1.76], P-trend = 0.04), and t-18:2 (1.41 [1.05-1.89], P-trend = 0.02). After further adjustment for other dietary habits, however, the associations of estimated dietary TFA with DM were attenuated, and only nonsignificant positive trends remained.

CONCLUSIONS: Among older adults, plasma phospholipid t-16:1n9 and t-18:1 levels were positively related to DM after adjustment for de novo lipogenesis fatty acids. Estimated dietary TFA was not significantly associated with DM. These findings highlight the need for further observational, interventional, and experimental studies of the effects TFA on DM.

VL - 38 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25784660?dopt=Abstract ER - TY - JOUR T1 - Plasma phospholipid very-long-chain saturated fatty acids and incident diabetes in older adults: the Cardiovascular Health Study. JF - Am J Clin Nutr Y1 - 2015 A1 - Lemaitre, Rozenn N A1 - Fretts, Amanda M A1 - Sitlani, Colleen M A1 - Biggs, Mary L A1 - Mukamal, Kenneth A1 - King, Irena B A1 - Song, Xiaoling A1 - Djoussé, Luc A1 - Siscovick, David S A1 - McKnight, Barbara A1 - Sotoodehnia, Nona A1 - Kizer, Jorge R A1 - Mozaffarian, Dariush KW - Aged KW - Aged, 80 and over KW - Biomarkers KW - Cross-Sectional Studies KW - Diabetes Mellitus KW - Diet KW - Eicosanoic Acids KW - Fatty Acids KW - Fatty Acids, Nonesterified KW - Female KW - Follow-Up Studies KW - Humans KW - Incidence KW - Male KW - Observational Studies as Topic KW - Palmitic Acid KW - Phospholipids KW - Prospective Studies KW - Risk Factors KW - Triglycerides AB -

BACKGROUND: Circulating saturated fatty acids (SFAs) are integrated biomarkers of diet and metabolism that may influence the pathogenesis of diabetes. In epidemiologic studies, circulating levels of palmitic acid (16:0) are associated with diabetes; however, very-long-chain SFAs (VLSFAs), with 20 or more carbons, differ from palmitic acid in their biological activities, and little is known of the association of circulating VLSFA with diabetes.

OBJECTIVE: By using data from the Cardiovascular Health Study, we examined the associations of plasma phospholipid VLSFA levels measured at baseline with subsequent incident diabetes.

DESIGN: A total of 3179 older adults, with a mean age of 75 y at study baseline (1992-1993), were followed through 2011. We used multiple proportional hazards regression to examine the associations of arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) with diabetes.

RESULTS: Baseline levels of each VLSFA were cross-sectionally associated with lower triglyceride levels and lower circulating palmitic acid. We identified 284 incident diabetes cases during follow-up. Compared with the lowest quartile, levels of arachidic acid in the highest quartile of the fatty acid distribution were associated with a 47% lower risk of diabetes (95% CI: 23%, 63%; P-trend: <0.001), after adjustment for demographics, lifestyle factors, and clinical conditions. In analogous comparisons, levels of behenic and lignoceric acid were similarly associated with 33% (95% CI: 6%, 53%; P-trend: 0.02) and 37% (95% CI: 11%, 55%; P-trend: 0.01) lower diabetes risk, respectively. Adjustment for triglycerides and palmitic acid attenuated the associations toward the null, and only the association of arachidic acid remained statistically significant (32% lower risk for fourth vs. first quartile; P-trend: 0.04).

CONCLUSIONS: These results suggest that circulating VLSFAs are associated with a lower risk of diabetes, and these associations may be mediated by lower triglycerides and palmitic acid. The study highlights the need to distinguish the effects of different SFAs and to explore determinants of circulating VLSFAs. This trial was registered at clinicaltrials.gov as NCT00005133.

VL - 101 IS - 5 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25787996?dopt=Abstract ER - TY - JOUR T1 - Prospective association of fatty acids in the de novo lipogenesis pathway with risk of type 2 diabetes: the Cardiovascular Health Study. JF - Am J Clin Nutr Y1 - 2015 A1 - Ma, Wenjie A1 - Wu, Jason H Y A1 - Wang, Qianyi A1 - Lemaitre, Rozenn N A1 - Mukamal, Kenneth J A1 - Djoussé, Luc A1 - King, Irena B A1 - Song, Xiaoling A1 - Biggs, Mary L A1 - Delaney, Joseph A A1 - Kizer, Jorge R A1 - Siscovick, David S A1 - Mozaffarian, Dariush KW - Aged KW - Biomarkers KW - Cohort Studies KW - Cross-Sectional Studies KW - Diabetes Mellitus, Type 2 KW - Female KW - Follow-Up Studies KW - Humans KW - Incidence KW - Lipogenesis KW - Liver KW - Male KW - Palmitic Acid KW - Phospholipids KW - Prevalence KW - Proportional Hazards Models KW - Risk Factors KW - Stearic Acids KW - United States KW - Up-Regulation AB -

BACKGROUND: Experimental evidence suggests that hepatic de novo lipogenesis (DNL) affects insulin homeostasis via synthesis of saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs). Few prospective studies have used fatty acid biomarkers to assess associations with type 2 diabetes.

OBJECTIVES: We investigated associations of major circulating SFAs [palmitic acid (16:0) and stearic acid (18:0)] and MUFA [oleic acid (18:1n-9)] in the DNL pathway with metabolic risk factors and incident diabetes in community-based older U.S. adults in the Cardiovascular Health Study. We secondarily assessed other DNL fatty acid biomarkers [myristic acid (14:0), palmitoleic acid (16:1n-7), 7-hexadecenoic acid (16:1n-9), and vaccenic acid (18:1n-7)] and estimated dietary SFAs and MUFAs.

DESIGN: In 3004 participants free of diabetes, plasma phospholipid fatty acids were measured in 1992, and incident diabetes was identified by medication use and blood glucose. Usual diets were assessed by using repeated food-frequency questionnaires. Multivariable linear and Cox regression were used to assess associations with metabolic risk factors and incident diabetes, respectively.

RESULTS: At baseline, circulating palmitic acid and stearic acid were positively associated with adiposity, triglycerides, inflammation biomarkers, and insulin resistance (P-trend < 0.01 each), whereas oleic acid showed generally beneficial associations (P-trend < 0.001 each). During 30,763 person-years, 297 incident diabetes cases occurred. With adjustment for demographics and lifestyle, palmitic acid (extreme-quintile HR: 1.89; 95% CI: 1.27, 2.83; P-trend = 0.001) and stearic acid (HR: 1.62; 95% CI: 1.09, 2.41; P-trend = 0.006) were associated with higher diabetes risk, whereas oleic acid was not significantly associated. In secondary analyses, vaccenic acid was inversely associated with diabetes (HR: 0.56; 95% CI: 0.38, 0.83; P-trend = 0.005). Other fatty acid biomarkers and estimated dietary SFAs or MUFAs were not significantly associated with incident diabetes.

CONCLUSIONS: In this large prospective cohort, circulating palmitic acid and stearic acid were associated with higher diabetes risk, and vaccenic acid was associated with lower diabetes risk. These results indicate a need for additional investigation of biological mechanisms linking specific fatty acids in the DNL pathway to the pathogenesis of diabetes.

VL - 101 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25527759?dopt=Abstract ER - TY - JOUR T1 - Associations of Plasma Phospholipid SFAs with Total and Cause-Specific Mortality in Older Adults Differ According to SFA Chain Length. JF - J Nutr Y1 - 2016 A1 - Fretts, Amanda M A1 - Mozaffarian, Dariush A1 - Siscovick, David S A1 - King, Irena B A1 - McKnight, Barbara A1 - Psaty, Bruce M A1 - Rimm, Eric B A1 - Sitlani, Colleen A1 - Sacks, Frank M A1 - Song, Xiaoling A1 - Sotoodehnia, Nona A1 - Spiegelman, Donna A1 - Lemaitre, Rozenn N KW - Aged KW - Aged, 80 and over KW - Cause of Death KW - Diet KW - Dietary Fats KW - Eicosanoic Acids KW - Fatty Acids KW - Female KW - Humans KW - Male KW - Mortality KW - Palmitic Acid KW - Phospholipids KW - Prospective Studies KW - Risk Factors KW - Stearic Acids AB -

BACKGROUND: Not much is known about the relations of circulating saturated fatty acids (SFAs), which are influenced by both metabolic and dietary determinants, with total and cause-specific mortality.

OBJECTIVE: We examined the associations of plasma phospholipid SFAs with total and cause-specific mortality among 3941 older adults from the Cardiovascular Health Study, a population-based prospective study of adults aged ≥65 y who were followed from 1992 through 2011.

METHODS: The relations of total and cause-specific mortality with plasma phospholipid palmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) were assessed using Cox proportional hazards models.

RESULTS: During 45,450 person-years of follow-up, 3134 deaths occurred. Higher concentrations of the plasma phospholipid SFAs 18:0, 22:0, and 24:0 were associated with a lower risk of total mortality [multivariable-adjusted HRs (95% CIs)] for the top compared with the bottom quintile: 0.85 (0.75, 0.95) for 18:0; 0.85 (0.75, 0.95) for 22:0; and 0.80 (0.71, 0.90) for 24:0. In contrast, plasma 16:0 concentrations in the highest quintile were associated with a higher risk of total mortality compared with concentrations in the lowest quintile [1.25 (1.11, 1.41)]. We also found no association of plasma phospholipid 20:0 with total mortality.

CONCLUSIONS: These findings suggest that the associations of plasma phospholipid SFAs with the risk of death differ according to SFA chain length and support future studies to better characterize the determinants of circulating SFAs and to explore the mechanisms underlying these relations.

VL - 146 IS - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26701797?dopt=Abstract ER - TY - JOUR T1 - Circulating Very Long-Chain Saturated Fatty Acids and Heart Failure: The Cardiovascular Health Study. JF - J Am Heart Assoc Y1 - 2018 A1 - Lemaitre, Rozenn N A1 - McKnight, Barbara A1 - Sotoodehnia, Nona A1 - Fretts, Amanda M A1 - Qureshi, Waqas T A1 - Song, Xiaoling A1 - King, Irena B A1 - Sitlani, Colleen M A1 - Siscovick, David S A1 - Psaty, Bruce M A1 - Mozaffarian, Dariush AB -

Background Circulating very-long-chain saturated fatty acids ( VLSFAs ) are integrated biomarkers of diet and metabolism that may point to new risk pathways and potential targets for heart failure ( HF ) prevention. The associations of VLSFA to HF in humans are not known. Methods and Results Using a cohort study design, we studied the associations of serially measured plasma phospholipid VLSFA with incident HF in the Cardiovascular Health Study. We investigated the associations of time-varying levels of the 3 major circulating VLSFAs , lignoceric acid (24:0), behenic acid (22:0), and arachidic acid (20:0), with the risk of incident HF using Cox regression. During 45030 person-years among 4249 participants, we identified 1304 cases of incident HF , including 489 with preserved and 310 with reduced ejection fraction. Adjusting for major HF risk factors and other circulating fatty acids, higher levels of each VLSFAs were associated with lower risk of incident HF ( P trend≤0.0007 each). The hazard ratio comparing the highest quintile to the lowest quintile was 0.67 (95% confidence interval, 0.55-0.81) for 24:0, 0.72 (95% confidence interval, 0.60-0.87) for 22:0 and 0.72 (95% confidence interval, 0.59-0.88) for 20:0. The associations were similar in subgroups defined by sex, age, body mass index, coronary heart disease, and diabetes mellitus. Among those with ejection fraction data, the associations appeared similar for those with preserved and with reduced ejection fraction. Conclusions Higher levels of circulating VLSFAs are associated with lower risk of incident HF in older adults. These novel associations should prompt further research on the role of VLSFA in HF , including relevant new risk pathways. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT 00005133.

VL - 7 IS - 21 ER - TY - JOUR T1 - Serial circulating omega 3 polyunsaturated fatty acids and healthy ageing among older adults in the Cardiovascular Health Study: prospective cohort study. JF - BMJ Y1 - 2018 A1 - Lai, Heidi Tm A1 - de Oliveira Otto, Marcia C A1 - Lemaitre, Rozenn N A1 - McKnight, Barbara A1 - Song, Xiaoling A1 - King, Irena B A1 - Chaves, Paulo Hm A1 - Odden, Michelle C A1 - Newman, Anne B A1 - Siscovick, David S A1 - Mozaffarian, Dariush AB -

OBJECTIVE: To determine the longitudinal association between serial biomarker measures of circulating omega 3 polyunsaturated fatty acid (n3-PUFA) levels and healthy ageing.

DESIGN: Prospective cohort study.

SETTING: Four communities in the United States (Cardiovascular Health Study) from 1992 to 2015.

PARTICIPANTS: 2622 adults with a mean (SD) age of 74.4 (4.8) and with successful healthy ageing at baseline in 1992-93.

EXPOSURE: Cumulative levels of plasma phospholipid n3-PUFAs were measured using gas chromatography in 1992-93, 1998-99, and 2005-06, expressed as percentage of total fatty acids, including α-linolenic acid from plants and eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid from seafoood.

MAIN OUTCOME MEASURE: Healthy ageing defined as survival without chronic diseases (ie, cardiovascular disease, cancer, lung disease, and severe chronic kidney disease), the absence of cognitive and physical dysfunction, or death from other causes not part of the healthy ageing outcome after age 65. Events were centrally adjudicated or determined from medical records and diagnostic tests.

RESULTS: Higher levels of long chain n3-PUFAs were associated with an 18% lower risk (95% confidence interval 7% to 28%) of unhealthy ageing per interquintile range after multivariable adjustments with time-varying exposure and covariates. Individually, higher eicosapentaenoic acid and docosapentaenoic acid (but not docosahexaenoic acid) levels were associated with a lower risk: 15% (6% to 23%) and 16% (6% to 25%), respectively. α-linolenic acid from plants was not noticeably associated with unhealthy ageing (hazard ratio 0.92, 95% confidence interval 0.83 to 1.02).

CONCLUSIONS: In older adults, a higher cumulative level of serially measured circulating n3-PUFAs from seafood (eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid), eicosapentaenoic acid, and docosapentaenoic acid (but not docosahexaenoic acid from seafood or α-linolenic acid from plants) was associated with a higher likelihood of healthy ageing. These findings support guidelines for increased dietary consumption of n3-PUFAs in older adults.

VL - 363 ER - TY - JOUR T1 - Serial measures of circulating biomarkers of dairy fat and total and cause-specific mortality in older adults: the Cardiovascular Health Study. JF - Am J Clin Nutr Y1 - 2018 A1 - de Oliveira Otto, Marcia C A1 - Lemaitre, Rozenn N A1 - Song, Xiaoling A1 - King, Irena B A1 - Siscovick, David S A1 - Mozaffarian, Dariush AB -

Background: Controversy has emerged about the benefits compared with harms of dairy fat, including concerns over long-term effects. Previous observational studies have assessed self-reported estimates of consumption or a single biomarker measure at baseline, which may lead to suboptimal estimation of true risk.

Objective: The aim of this study was to investigate prospective associations of serial measures of plasma phospholipid fatty acids pentadecanoic (15:0), heptadecanoic (17:0), and trans-palmitoleic (trans-16:1n-7) acids with total mortality, cause-specific mortality, and cardiovascular disease (CVD) risk among older adults.

Design: Among 2907 US adults aged ≥65 y and free of CVD at baseline, circulating fatty acid concentrations were measured serially at baseline, 6 y, and 13 y. Deaths and CVD events were assessed and adjudicated centrally. Prospective associations were assessed by multivariate-adjusted Cox models incorporating time-dependent exposures and covariates.

Results: During 22 y of follow-up, 2428 deaths occurred, including 833 from CVD, 1595 from non-CVD causes, and 1301 incident CVD events. In multivariable models, circulating pentadecanoic, heptadecanoic, and trans-palmitoleic acids were not significantly associated with total mortality, with extreme-quintile HRs of 1.05 for pentadecanoic (95% CI: 0.91, 1.22), 1.07 for heptadecanoic (95% CI: 0.93, 1.23), and 1.05 for trans-palmitoleic (95% CI: 0.91, 1.20) acids. Circulating heptadecanoic acid was associated with lower CVD mortality (extreme-quintile HR: 0.77; 95% CI: 0.61, 0.98), especially stroke mortality, with a 42% lower risk when comparing extreme quintiles of heptadecanoic acid concentrations (HR: 0.58; 95% CI: 0.35, 0.97). In contrast, heptadecanoic acid was associated with a higher risk of non-CVD mortality (HR: 1.27; 95% CI: 1.07, 1.52), which was not clearly related to any single subtype of non-CVD death. No significant associations of pentadecanoic, heptadecanoic, or trans-palmitoleic acids were seen for total incident CVD, coronary heart disease, or stroke.

Conclusions: Long-term exposure to circulating phospholipid pentadecanoic, heptadecanoic, or trans-palmitoleic acids was not significantly associated with total mortality or incident CVD among older adults. High circulating heptadecanoic acid was inversely associated with CVD and stroke mortality and potentially associated with higher risk of non-CVD death.

ER - TY - JOUR T1 - Serial Plasma Phospholipid Fatty Acids in the De Novo Lipogenesis Pathway and Total Mortality, Cause-Specific Mortality, and Cardiovascular Diseases in the Cardiovascular Health Study. JF - J Am Heart Assoc Y1 - 2019 A1 - Lai, Heidi T M A1 - de Oliveira Otto, Marcia C A1 - Lee, Yujin A1 - Wu, Jason H Y A1 - Song, Xiaoling A1 - King, Irena B A1 - Psaty, Bruce M A1 - Lemaitre, Rozenn N A1 - McKnight, Barbara A1 - Siscovick, David S A1 - Mozaffarian, Dariush AB -

Background Synthesized fatty acids (FAs) from de novo lipogenesis may affect cardiometabolic health, but longitudinal associations between serially measured de novo lipogenesis-related fatty acid biomarkers and mortality or cardiovascular disease (CVD) are not well established. Methods and Results We investigated longitudinal associations between de novo lipogenesis-related fatty acids with all-cause mortality, cause-specific mortality, and incident CVD among 3869 older US adults, mean (SD) age 75 (5) years and free of prevalent CVD at baseline. Levels of plasma phospholipid palmitic (16:0), palmitoleic (16:1n-7), stearic (18:0), oleic acid (18:1n-9), and other risk factors were serially measured at baseline, 6 years, and 13 years. All-cause mortality, cause-specific mortality, and incident fatal and nonfatal CVD were centrally adjudicated. Risk was assessed in multivariable-adjusted Cox models with time-varying FAs and covariates. During 13 years, median follow-up (maximum 22.4 years), participants experienced 3227 deaths (1131 CVD, 2096 non-CVD) and 1753 incident CVD events. After multivariable adjustment, higher cumulative levels of 16:0, 16:1n-7, and 18:1n-9 were associated with higher all-cause mortality, with extreme-quintile hazard ratios (95% CIs) of 1.35 (1.17-1.56), 1.40 (1.21-1.62), and 1.56 (1.35-1.80), respectively, whereas higher levels of 18:0 were associated with lower mortality (hazard ratio=0.76; 95% CI=0.66-0.88). Associations were generally similar for CVD mortality versus non-CVD mortality, as well as total incident CVD. Changes in levels of 16:0 were positively, and 18:0 inversely, associated with all-cause mortality (hazard ratio=1.23, 95% CI=1.08-1.41; and hazard ratio=0.78, 95% CI=0.68-0.90). Conclusions Higher long-term levels of 16:0, 16:1n-7, and 18:1n-9 and changes in 16:0 were positively, whereas long-term levels and changes in 18:0 were inversely, associated with all-cause mortality in older adults.

VL - 8 IS - 22 ER - TY - JOUR T1 - Serial Biomarkers of De Novo Lipogenesis Fatty Acids and Incident Heart Failure in Older Adults: The Cardiovascular Health Study. JF - J Am Heart Assoc Y1 - 2020 A1 - Lee, Yujin A1 - Lai, Heidi T M A1 - de Oliveira Otto, Marcia C A1 - Lemaitre, Rozenn N A1 - McKnight, Barbara A1 - King, Irena B A1 - Song, Xiaoling A1 - Huggins, Gordon S A1 - Vest, Amanda R A1 - Siscovick, David S A1 - Mozaffarian, Dariush AB -

Background De novo lipogenesis (DNL) is an endogenous pathway that converts excess dietary starch, sugar, protein, and alcohol into specific fatty acids (FAs). Although elevated DNL is linked to several metabolic abnormalities, little is known about how long-term habitual levels and changes in levels of FAs in the DNL pathway relate to incident heart failure (HF). Methods and Results We investigated whether habitual levels and changes in serial measures of FAs in the DNL pathway were associated with incident HF among 4249 participants free of HF at baseline. Plasma phospholipid FAs were measured at baseline, 6 years, and 13 years using gas chromatography, and risk factors for HF were measured using standardized methods. Incident HF was centrally adjudicated using medical records. We prospectively evaluated associations with HF risk of (1) habitual FA levels, using cumulative updating to assess long-term exposure, and (2) changes in FA levels over time. During 22.1 years of follow-up, 1304 HF cases occurred. After multivariable adjustment, habitual levels and changes in levels of palmitic acid (16:0) were positively associated with incident HF (interquintile hazard ratio [95% CI]=1.17 [1.00-1.36] and 1.26 [1.03-1.55], respectively). Changes in levels of 7-hexadecenoic acid (16:1n-9) and vaccenic acid (18:1n-7) were each positively associated with risk of HF (1.36 [1.13-1.62], and 1.43 [1.18-1.72], respectively). Habitual levels and changes in levels of myristic acid (14:0), palmitoleic acid (16:1n-7), stearic acid (18:0), and oleic acid (18:1n-9) were not associated with incident HF. Conclusions Both habitual levels and changes in levels of 16:0 were positively associated with incident HF in older adults. Changes in 16:1n-9 and 18:1n-7 were also positively associated with incident HF. These findings support a potential role of DNL or these DNL-related FAs in the development of HF.

VL - 9 IS - 4 ER - TY - JOUR T1 - Assessment of Plasma Phospholipid Very-Long-Chain Saturated Fatty Acid Levels and Healthy Aging. JF - JAMA Netw Open Y1 - 2021 A1 - Bockus, Lee B A1 - Biggs, Mary L A1 - Lai, Heidi T M A1 - de Olivera Otto, Marcia C A1 - Fretts, Amanda M A1 - McKnight, Barbara A1 - Sotoodehnia, Nona A1 - King, Irena B A1 - Song, Xiaoling A1 - Siscovick, David S A1 - Mozaffarian, Dariush A1 - Lemaitre, Rozenn N AB -

Importance: Identifying novel factors that protect against age-related diseases and promote healthy aging is critical to public health. Higher levels of circulating very-long-chain saturated fatty acids (VLSFAs) are integrated biomarkers of diet and metabolism shown to have beneficial associations in cardiovascular disease and total mortality, but whether they are associated with overall healthy aging is unknown.

Objective: To examine the association of circulating levels of 3 VLSFAs with unhealthy aging events, including incident chronic disease (cardiovascular disease, cancer, lung disease or severe kidney disease), physical dysfunction, and cognitive decline.

Design, Setting, and Participants: This cohort study used 1992 to 2014 data from the Cardiovascular Health Study (CHS). The CHS is a multicenter, population-based study of cardiovascular disease among older adults. Among the 4559 CHS participants with available fatty acid data, 1879 participants who had an age-related event before their first measurement were excluded. Data analysis was performed in 2020.

Main Outcomes and Measures: Plasma phospholipid VLSFA levels were measured by thin-layer chromatography followed by gas chromatography. The main outcome was the hazard ratio (HR) of an incident unhealthy aging event associated with serial measures of plasma arachidic acid, behenic acid, and lignoceric acid.

Results: Among the 2680 study participants (976 men [36.4%]), the mean (SD) age was 74.7 (4.8) years old at entry. During a median (interquartile range) of 6.4 (2.9-12.9) years of follow-up, 2484 participants experienced an unhealthy event. Compared with the lowest quintile, levels of behenic acid in the highest quintile of the fatty acid distribution were associated with 15% lower risk of an unhealthy event (HR, 0.85; 95% CI, 0.74-0.97; P for trend = .01) after adjustment for demographic characteristics, lifestyle factors, and clinical conditions. In analogous comparisons, levels of lignoceric acid were similarly associated with 16% lower risk of an unhealthy event (HR, 0.84; 95% CI, 0.73-0.95; P for trend = .001).

Conclusions and Relevance: These findings suggest that higher levels of circulating behenic acid and lignoceric acid are associated with lower risk of unhealthy aging events. These results highlight the need to explore determinants of circulating VLSFAs for potential novel efforts to promote healthy aging.

VL - 4 IS - 8 ER - TY - JOUR T1 - Circulating Omega-3 and Omega-6 Fatty Acids, Cognitive Decline, and Dementia in Older Adults. JF - J Alzheimers Dis Y1 - 2023 A1 - de Oliveira Otto, Marcia C A1 - Wu, Jason H Y A1 - Thacker, Evan L A1 - Lai, Heidi Tsz Mung A1 - Lemaitre, Rozenn N A1 - Padhye, Nikhil A1 - Song, Xiaoling A1 - King, Irena B A1 - Lopez, Oscar A1 - Siscovick, David S A1 - Mozaffarian, Dariush AB -

BACKGROUND: Comprising nearly 35% of brain lipids, polyunsaturated fatty acids (PUFA) are essential for optimal brain function. However, the role of PUFA on cognitive health outcomes later in life is largely unknown.

OBJECTIVE: We investigated prospective associations of plasma phospholipid omega-3 (ALA [18 : 3], EPA [20 : 5], DPA [22 : 5], DHA [22 : 6]) and omega-6 (LA [18 : 2], AA [20 : 4]) PUFA with cognitive decline, risk of cognitive impairment and dementia among adults aged≥65 years in the Cardiovascular Health Study.

METHODS: Circulating fatty acid concentrations were measured serially at baseline (1992/1993), 6 years, and 13 years later. Cognitive decline and impairment were assessed using the 100-point Modified Mini-Mental State Examination (3MSE) up to 7 times. Clinical dementia was identified using adjudicated neuropsychological tests, and ICD-9 codes.

RESULTS: Among 3,564 older adults free of stroke and dementia at baseline, cognitive function declined annually by approximately -0.5 3MSE points; 507 participants developed cognitive impairment and 499 dementia over up to 23 years of follow-up. In multivariable models, higher circulating arachidonic acid (AA) concentrations were associated with slower cognitive decline and lower dementia risk, with associations growing stronger with greater length of follow-up (hazard ratio [HR,95% CI] of dementia per interquintile range, 0.74 [0.56-0.97] at 5 years, and 0.53 [0.37-0.77] at 15 years). Circulating docosapentaenoic (DPA) concentrations were associated with slower cognitive decline and lower risk of cognitive impairment (extreme-quintile HR, 0.72 [95% CI: 0.55, 0.95]). Findings were generally null or inconsistent for other omega-3 or omega-6 PUFA.

CONCLUSION: Circulating AA and DPA, but not other PUFA, are associated with slower rate of cognitive decline and lower risk of dementia or cognitive impairment later in life.

ER -