Abstract P039: Longitudinal measures of serial plasma phospholipid de novo lipogenesis fatty acids and incident congestive heart failure in older adults: The Cardiovascular Health Study

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Yujin Lee ◽  
Heidi T Lai ◽  
Marcia C de Oliveira Otto ◽  
Rozenn N Lemaitre ◽  
Xiaoling Song ◽  
...  
Keyword(s):  
Heart Failure ◽  
Older Adults ◽  
Fatty Acids ◽  
Congestive Heart Failure ◽  
De Novo ◽  
Plasma Phospholipid ◽  
De Novo Lipogenesis ◽  
Cardiovascular Health Study ◽  
Longitudinal Changes ◽  
Time Varying Covariates

Introduction: De novo lipogenesis (DNL) is an endogenous pathway for converting excess carbohydrates and proteins into fatty acids (FAs). While elevated DNL is linked to several metabolic abnormalities, little is known about associations of longitudinal changes in DNL FAs with incident congestive heart failure (CHF), a growing condition in older adults. Methods: We investigated relations of longitudinal changes in DNL FAs, measured at year 0, year 6, and year 13, with incident CHF using serial measures of plasma phospholipid myristic acid (14:0), palmitic acid (16:0), 7-hexadecenoic acid (16:1n-9), palmitoleic acid (16:1n-7), stearic acid (18:0), oleic acid (18:1n-9), and cis-vaccenic acid (18:1n-7). Time-varying covariates were measured using standardized methods in 2,005 older adults with two or more FA measures and free of CHF at baseline. Incident CHF was centrally adjudicated using medical records. Risk was assessed by multivariable-adjusted Cox proportional hazards. Results: During 14,628 person-years, 553 CHF events occurred. After multivariate adjustment, serial changes in 16:0, 16:1n-9, and 18:1n-7 were positively associated with incident CHF, with HRs (95% CI) for each 30% change in levels of 2.84 (1.50, 5.37), 1.16 (1.00, 1.33), and 1.42 (1.15, 1.77), respectively ( Table ). Findings were similar in sensitivity analyses excluding individuals with prevalent coronary heart disease (not shown). In analyses evaluating absolute, rather than changes in, DNL FA levels, the associations of 16:0, 16:1n-9, and 18:1n-7 with incident CHF were no longer statistically significant although with consistent directions of association (not shown). Neither changes nor absolute levels of 14:0, 16:1n-7, 18:0, and 18:1n-9 were associated with CHF. Conclusion: Serial changes in plasma phospholipid 16:0, 16:1n-9, and 18:1n-7 were associated with an elevated risk of CHF in older adults. These results indicate that potential mechanisms of risk, especially related to DNL, deserve further investigation.

Abstract 061: Long-chain monounsaturated fatty acids and congestive heart failure incidence: the Atherosclerosis Risk in Communities Study

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Fumiaki Imamura ◽  
Rozenn N Lemaitre ◽  
Lyn M Steffen ◽  
Aaron R Folsom ◽  
David S Siscovick ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Older Adults ◽  
Fatty Acids ◽  
Congestive Heart Failure ◽  
Plasma Phospholipid ◽  
Atherosclerosis Risk In Communities ◽  
Atherosclerosis Risk ◽  
Middle Aged Adults ◽  
Long Chain

Background: Animal experiments in 1970s demonstrated direct cardiotoxicity of long-chain monounsaturated fatty acid (LCMUFA, 22:1 and 24:1 fatty acids) consumption. We recently found plasma phospholipid 22:1 and 24:1 to be associated with 34% and 75% higher risk (quintiles 5 vs. 1), respectively, of congestive heart failure (CHF) among older adults in the Cardiovascular Health Study. We wished to validate these results in a second independent cohort of middle-aged adults. Methods: We evaluated 3,577 adults free of CHF at baseline (age=54.1±5.8) in the Minnesota subcohort of the Atherosclerosis Risk in Communities Study (ARIC) in whom plasma phospholipid LCMUFA were measured. Incident CHF was ascertained from 1988 to 2008 by annual phone contacts, hospitalization discharge codes, and death certificates. Using multivariate Cox models, we evaluated prospective association of each LCMUFA with incident CHF, and potential mediation via CHF risk factors, including ECG left ventricular hypertrophy, and incident coronary heart disease (CHD). As a negative control, we also evaluated incident stroke, given its many shared risk factors for CHF but no link to potentially direct cardiotoxicity. Results: Mean±SD plasma phospholipid levels (% of total fatty acids) of 22:1 and 24:1 were 0.01±0.03 and 0.58±0.17. Over the 64,438 person-years of follow-up, 330 CHF events occurred. After multivariable adjustment, higher levels of 22:1 and 24:1 were associated with higher risk of CHF (Figure). Hazard ratios (95%CI) for quintiles 5 vs. 1 of 22:1 and 24:1 levels were 1.57 (1.11–2.23) and 1.92 (1.22–3.03) (p trend=0.03 and 0.002), respectively. These associations were only partly attenuated by potential mediators, including incident CHD. Neither LCMUFA was associated with incident stroke (not shown). Conclusions: Higher 22:1 and 24:1 LCMUFA levels were associated with CHF risk in middle-aged adults, consistent with our prior findings in older adults. These findings support the possibility of clinical cardiotoxicity of LCMUFA in humans.

Abstract MP023: Novel Patterns of Circulating Fatty Acids and Risk of Cardiovascular Disease: the Cardiovascular Health Study

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Fumiaki Imamura ◽  
Rozenn N Lemaitre ◽  
Irena B King ◽  
Xiaoling Song ◽  
Alice H Lichtenstein ◽  
...  
Keyword(s):  
Older Adults ◽  
Fatty Acids ◽  
Coronary Stenosis ◽  
Cardiovascular Health ◽  
De Novo ◽  
Disease Risk ◽  
De Novo Lipogenesis ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Trans Fa

Background: Circulating fatty acids (FA) reflect complex interrelations of diet and metabolism. Few studies have evaluated circulating FA as patterns related to cardiovascular diseases (CVD). Methods: We applied principal component analysis (PCA) to 39 plasma phospholipid FA measured in 2,972 older adults (mean age=72.1) at baseline (1992) in the Cardiovascular Health Study, and derived FA patterns. We evaluated prospective associations of identified FA patterns with 14-year incidence of CVD, adjudicated by centralized committee, using multivariate Cox proportional hazards corrected for regression dilution bias. The CHS-derived FA patterns were evaluated in a separate cohort for associations with angiographically-defined atherosclerosis progression over 3.5 years in 1,912 coronary segments of 228 postmenopausal women (mean age=65.4) with established CHD, including FA in phospholipids, triglycerides, and cholesteryl esters. Results: Three distinct patterns were identified, that we characterized as having higher trans FA (TFA pattern), de novo lipogenesis FA (DNL pattern), and dairy and long-chain monounsaturated FA (dairy-LCMUFA pattern). During 32,265 person-years, 780 CVD events occurred, including 512 CHD and 346 stroke. The TFA pattern was associated with higher CVD risk (HR for quintiles 5 vs. 1=2.47 [95% CI 1.35–4.51]; p trend=0.006) (Figure), primarily due to stroke (HR=4.68 [1.85–11.8]; p trend=0.003) but not CHD (HR=1.08 [0.50–2.32]; p trend=0.6). The DNL and dairy-LCMUFA patterns were not associated with CVD, or with CHD or stroke examined separately (p>0.1). In the second cohort, the TFA pattern, but not the other 2 patterns, in all lipid compartments was positively associated with progression of coronary stenosis (p trend<0.05). Conclusions: Our results suggest PCA can derive informative FA patterns for assessing disease risk. A pattern mainly reflecting higher trans FA levels is linked to higher risk of stroke in older adults, and coronary stenosis progression in women with CHD.

scholarly journals Circulating Long-Chain ω-3 Fatty Acids and Incidence of Congestive Heart Failure in Older Adults: The Cardiovascular Health Study

2011 ◽  
Vol 155 (3) ◽  
pp. 160 ◽  
Author(s):  
Dariush Mozaffarian ◽  
Rozenn N. Lemaitre ◽  
Irena B. King ◽  
Xiaoling Song ◽  
Donna Spiegelman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Older Adults ◽  
Fatty Acids ◽  
Congestive Heart Failure ◽  
Cardiovascular Health ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Long Chain

Abstract MP06: Circulating Fatty Acids in the De Novo Lipogenesis Pathway and Total and Cause-Specific Mortality Among Older Adults: The Cardiovascular Health Study

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Heidi T Lai ◽  
Marcia C de Oliveira Otto ◽  
Jason H Wu ◽  
Yujin Lee ◽  
Xiaoling Song ◽  
...  
Keyword(s):  
Older Adults ◽  
Fatty Acids ◽  
De Novo ◽  
Total Mortality ◽  
De Novo Lipogenesis ◽  
Cardiovascular Health Study ◽  
Specific Mortality ◽  
Changes Over Time ◽  
Over Time

De novo lipogenesis (DNL) is a crucial metabolic pathway that convert excess carbohydrates to fatty acids (FA) for energy and storage. Both DNL and the synthesized FA have biologic effects that may affect cardiometabolic risk. Yet, the association between DNL FA and mortality and CVD are not well-established in older adults, especially using serial biomarkers which objectively allow more accurate estimates of long-term FA exposure, as well as changes over time. We investigated the longitudinal association between serial levels of circulating DNL FA and total mortality, cause-specific mortality, and total CVD among 3,869 older U.S. adults (mean age 75 y) free of prevalent CVD at baseline. Levels of plasma phospholipid palmitic (16:0), palmitoleic (16:1n-7), stearic (18:0), and oleic acid (18:1n-9) were quantified at baseline, year 6, and year 13. Outcomes were centrally adjudicated using multiple sources. Risk was assessed in multivariable-adjusted Cox models with time-varying FA and covariates. During 46,974 person-years, 3,227 deaths (including 1,131 from CVD, 2,096 from non-CVD causes) and 1,754 incident total CVD events occurred. After multivariable-adjustment, cumulative levels of 16:0, 16:1n-7 and 18:1n-9 were each positively, while 18:0 was inversely, associated with total mortality ( Table ). Associations were generally similar for CVD vs. non-CVD mortality, and vs. total incident CVD (not shown). Among non-CVD deaths, associations for dementia and pulmonary deaths were generally similar to total mortality; while only 16:0 and 18:1n-9 were positively associated with cancer mortality. Higher long-term levels of circulating 16:0, 16:1n-7 and 18:1n-9 were positively, while 18:0 was inversely, associated with total mortality in older adults. Novel findings highlight the potential relevance of DNL later in life, and the need for further experimental research and interventions on the relevant underlying physiology and long-term health effects of DNL FA. Findings for FA changes over time to be presented.

Abstract P145: Circulating and Dietary Trans-Fatty Acids and Incident Type-2 Diabetes Mellitus in Older Adults: The Cardiovascular Health Study

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Qianyi Wang ◽  
Fumiaki Imamura ◽  
Wenjie Ma ◽  
Rozenn N Lemaitre ◽  
Irena B King ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Older Adults ◽  
Fatty Acids ◽  
Trans Fatty Acids ◽  
Cardiovascular Health ◽  
Plasma Phospholipid ◽  
Health Study ◽  
Cardiovascular Health Study

Background: While trans-fatty acids (TFA) influence CHD, their effects on type 2 diabetes mellitus (DM) are not established, with mixed findings of experimental, short-term intervention, and observational studies. Effects may vary depending on specific TFA subtype or method of assessment (circulating biomarkers vs. diet). Objectives: To examine prospective associations of circulating and estimated dietary TFA with risk of incident DM in older adults. Methods: Plasma phospholipid trans-(t-)16:1n9, total t-18:1, and cis/trans-(c/t-), t/c- and t/t-18:2(n6,9) were measured in blood stored among 3,076 adults in the Cardiovascular Health Study (CHS), aged 74±5y and free of prevalent DM in 1992. Dietary TFA was estimated among 4,246 adults free of prevalent DM when dietary questionnaires were initially administered in 1989 (n=3,917) or in 1996 (n=329). Incident DM up to 2009 was defined as new use of insulin or hypoglycemic drugs, fasting glucose≥126 mg/dL, nonfasting glucose≥200 mg/dL, or 2-hour post-challenge glucose≥200 mg/dL. The relative risk of incident DM associated with each TFA subtype was assessed using multivariate Cox proportional hazards regression. Results: Levels of each circulating TFA subtype varied from 2.00±0.73 (% of fatty acids) for t-18:1 to 0.05±0.02 for t/t-18:2. TFA subtypes were moderately to highly intercorrelated (r=0.4 to 0.8), except for t/t-18:2 which weakly correlated with all other TFAs (r<0.1). During 30,927 person-years, 364 DM cases occurred among participants with plasma phospholipid TFA measures. Adjusting for demographics, lifestyle factors, and medical history, lower DM risk was associated with higher levels of t-16:1n9 (Quartile 4 vs. Quartile 1 HR=0.76, p trend=0.03), total t-18:1 (HR=0.71, p trend=0.02) and t/t-18:2 (HR=0.73, p trend=0.04). However, further mutual adjustment for the different TFA subtypes attenuated these inverse associations, and none of the 5 circulating TFA biomarkers were independently related to incident DM (p trend≥0.14 for all). During 50,508 person-years in the dietary analyses, 453 DM cases occurred. Adjusting for demographics, lifestyle, medical history, and other dietary habits, increased DM risk was observed among participants with higher consumption of total TFA (Quartile 4 vs. Quartile 1 HR=1.40, p trend=0.04) and t-18:2 (HR=1.49, p trend=0.006), and t-18:1 consumption (HR=1.32, p trend=0.08), although the latter was not statistically significant. Conclusions: Plasma phospholipid TFA subtypes were not associated, whereas dietary total TFA and t-18:2 were positively associated, with incident DM among older adults. These findings highlight the need to understand how dietary TFA may influence DM and why associations may differ for circulating versus dietary TFAs.

Abstract MP005: Plasma Phospholipid Concentration of Palmitoleic Acid is Associated with an Increased Risk of Heart Failure in Male Physicians

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Luc Djousse ◽  
Natalie Weir ◽  
Gregory Kotler ◽  
Naomi Hanson ◽  
Michael Tsai ◽  
...  
Keyword(s):  
Heart Failure ◽  
Fatty Acids ◽  
Oleic Acid ◽  
Palmitoleic Acid ◽  
De Novo ◽  
Index Case ◽  
Vaccenic Acid ◽  
Plasma Phospholipid ◽  
Increased Risk ◽  
Stearoyl Coa Desaturase

Background: Plasma fatty acids in the de novo lipogenesis including plamitoleic acid have been associated with a higher risk of blood pressure and type 2 diabetes (two major risk factors for heart failure -HF). However, limited data are available on the association between plasma levels of palmitoleic acid and HF risk. Objective: To test the hypothesis that plasma palmitoleic acid concentration is associated with an increased risk of HF. In a secondary aim, we examined whether stearoyl-CoA desaturase indices, cis -vaccenic acid, and oleic acid were associated with HF risk. Methods: We used a prospective nested case-control design for this project among participants of the Physicians' Health Study. For each of the 788 HF cases, we used the risk set method to randomly select a control among all eligible controls at the time of the index case occurrence. Each control was matched on age, year of birth, race, and time of blood collection of the index case. We used gas chromatography to measure plasma phospolipid fatty acids on frozen blood samples collected between 1997 and 2001 on study subjects free of HF. HF events were ascertained via annual follow-up questionnaires and validated in a subsample through review of medical records (positive predictive value 91% -- 50 confirmed out of 55 self-reported cases). Results: Mean age was 58.7 ± 8.0 years. In a conditional logistic regression controlling for matching factors, odds ratios (95% CI) for HF were 1.0 (reference), 1.00 (0.75–1.33), 1.22 (0.91–1.64), and 1.48 (1.10–1.99) across consecutive quartiles of palmitoleic acid (p trend 0.005). Additional adjustment for body mass index, smoking, alcohol intake, exercise, prevalent diabetes and coronary disease, marine omega-3 fatty acids, hypertension treatment, and plasma stearic acid did not alter the results [OR: 1.0, 1.00 (0.72–1.37), 1.23 (0.89–1.72), and 1.51 (1.06–2.15) from the lowest to the highest quartile, p trend 0.014]. When analyzed as a continuous variable, each standard deviation increase of plasma palmitoleic acid was associated with a 15% higher odds of HF [OR: 1.15 (1.01–1.31)] in a multivariable adjusted model. In a secondary analysis, plasma phospholipid oleic acid (18:1n−9) and cis-vaccenic acid (18:1n−7) were not associated with the odds of HF. Indices of stearoyl-CoA desaturase-1 (16:1n−7 to 16:0 ratio) and desaturase-2 (18:1n−9 to 18:0 ratio) were not significantly associated with the odds of HF. Conclusion: Our data showed that plasma concentration of palmitoleic acid is positively associated with the risk of HF in male physicians. This suggests that fatty acids in the de novo lipogenesis may play a role in the development of HF.

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