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 - 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 - Changes in Depressive Symptoms and Subsequent Risk of Stroke in the Cardiovascular Health Study. JF - Stroke Y1 - 2016 A1 - Gilsanz, Paola A1 - Kubzansky, Laura D A1 - Tchetgen Tchetgen, Eric J A1 - Wang, Qianyi A1 - Kawachi, Ichiro A1 - Patton, Kristen K A1 - Fitzpatrick, Annette L A1 - Kop, Willem J A1 - Longstreth, W T A1 - Glymour, M Maria AB -

BACKGROUND AND PURPOSE: Depression is associated with stroke, but the effects of changes in depressive symptoms on stroke risk are not well understood. This study examined whether depressive symptom changes across 2 successive annual assessments were associated with incident stroke the following year.

METHODS: We used visit data from 4319 participants of the Cardiovascular Health Study who were stroke free at baseline to examine whether changes in depressive symptoms classified across 2 consecutive annual assessments predicted incident first stroke during the subsequent year. Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression scale (high versus low at ≥10). Survival models were inverse probability weighted to adjust for demographics, health behaviors, medical conditions, past depressive symptoms, censoring, and survival.

RESULTS: During follow-up, 334 strokes occurred. Relative to stable low scores of depressive symptoms, improved depression symptoms were associated with almost no excess risk of stroke (adjusted hazards ratio, 1.02; 95% confidence interval, 0.66-1.58). New-onset symptoms were nonsignificantly associated with elevated stroke risk (adjusted hazards ratio, 1.44; 95% confidence interval, 0.97-2.14), whereas persistently high depressive symptoms were associated with elevated adjusted hazard of all-cause stroke (adjusted hazards ratio, 1.65; 95% confidence interval, 1.06-2.56). No evidence for effect modification by race, age, or sex was found.

CONCLUSIONS: Persistently high symptoms of depression predicted elevated hazard of stroke. Participants with improved depressive symptoms had no elevation in stroke risk. Such findings suggest that strategies to reduce depressive symptoms may ameliorate stroke risk.

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