Serial Biomarkers of De Novo Lipogenesis Fatty Acids and Incident Heart Failure in Older Adults: The Cardiovascular Health Study

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.

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Prospective association of fatty acids in the de novo lipogenesis pathway with risk of type 2 diabetes: the Cardiovascular Health Study

American Journal of Clinical Nutrition ◽

10.3945/ajcn.114.092601 ◽

2014 ◽

Vol 101 (1) ◽

pp. 153-163 ◽

Cited By ~ 97

Author(s):

Wenjie Ma ◽

Jason HY Wu ◽

Qianyi Wang ◽

Rozenn N Lemaitre ◽

Kenneth J Mukamal ◽

...

Keyword(s):

Type 2 Diabetes ◽

Fatty Acids ◽

Cardiovascular Health ◽

De Novo ◽

De Novo Lipogenesis ◽

Health Study ◽

Cardiovascular Health Study ◽

Prospective Association

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Abstract 04: Incident Heart Failure and Longitudinal Cognitive Trajectories in the Cardiovascular Health Study

Circulation ◽

10.1161/circ.131.suppl_1.04 ◽

2015 ◽

Vol 131 (suppl_1) ◽

Author(s):

Christa Schank ◽

Natalie J Blades ◽

Sarwat I Chaudhry ◽

John A Dodson ◽

W T Longstreth ◽

...

Keyword(s):

Heart Failure ◽

Older Adults ◽

Cognitive Decline ◽

Cardiovascular Health ◽

Self Report ◽

Cognitive Test ◽

Health Study ◽

Cardiovascular Health Study ◽

Incident Heart Failure ◽

Rate Of Decline

OBJECTIVE: To determine whether older adults who develop incident heart failure (HF) experience faster cognitive decline than those without HF. METHODS: We analyzed longitudinal cognitive test data from the Cardiovascular Health Study, a community-based study of adults aged 65 years and older. Participants in this analysis did not have HF or history of stroke at baseline and were censored when they experienced incident clinical stroke. Incident HF was identified by self-report of physician-diagnosed HF and confirmed by adjudicated review of inpatient and outpatient medical records and medication use. Outcomes were mean score and rate of decline in mean score on the 100-point Modified Mini-Mental State Examination (3MSE), administered annually up to nine times from 1990 to 1998. A linear mixed effects model was used to model the relationship of cognitive decline with HF and age, adjusted for demographics, health behaviors, and comorbid conditions including hypertension and diabetes. RESULTS: Analyses included 5,211 participants with mean age 74 years at baseline, of whom 545 (10.5%) developed incident HF over a median follow-up of 7.8 years. Mean 3MSE score was lower at the time of HF diagnosis compared with no HF, and declined faster after incident HF compared with no HF. For example, at age 80, covariate-adjusted predicted mean 3MSE score was 88.6 points (95% CI: 88.3, 89.0) in participants without HF, but 87.6 points (95% CI: 87.3, 87.9) in those with newly diagnosed HF. Predicted five-year decline in mean 3MSE score from age 80 to age 85 was 5.9 points (95% CI: 5.7, 6.0) in participants without HF, but 10.0 points (95% CI: 8.6, 11.3) in those diagnosed with incident HF at age 80. Faster decline in 3MSE score after HF diagnosis was seen at all ages studied. The figure shows predicted mean 3MSE score trajectories without HF (solid line) and after HF diagnosed at ages 70, 75, 80, and 85 (dashed lines), with 95% CI shaded. CONCLUSIONS: Older adults diagnosed with incident HF experience faster average cognitive decline than those without HF.

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Systolic–diastolic hypertension versus isolated systolic hypertension and incident heart failure in older adults: Insights from the Cardiovascular Health Study

International Journal of Cardiology ◽

10.1016/j.ijcard.2017.02.139 ◽

2017 ◽

Vol 235 ◽

pp. 11-16 ◽

Cited By ~ 11

Author(s):

Apostolos Tsimploulis ◽

Helen M. Sheriff ◽

Phillip H. Lam ◽

Daniel J. Dooley ◽

Markus S. Anker ◽

...

Keyword(s):

Heart Failure ◽

Older Adults ◽

Systolic Hypertension ◽

Cardiovascular Health ◽

Health Study ◽

Cardiovascular Health Study ◽

Isolated Systolic Hypertension ◽

Diastolic Hypertension ◽

Incident Heart Failure

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ORTHOPNEA OR PAROXYSMAL NOCTURNAL DYSPNEA IN OLDER ADULTS WITHOUT PREVALENT HEART FAILURE IS A PREDICTOR, BUT NOT AN INDEPENDENT RISK FACTOR FOR INCIDENT HEART FAILURE: INSIGHTS FROM THE CARDIOVASCULAR HEALTH STUDY

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(17)34132-3 ◽

2017 ◽

Vol 69 (11) ◽

pp. 743

Author(s):

Apostolos Tsimploulis ◽

Poonam Bhyan ◽

Phillip Lam ◽

Daniel Dooley ◽

Javed Butler ◽

...

Keyword(s):

Heart Failure ◽

Older Adults ◽

Risk Factor ◽

Independent Risk Factor ◽

Cardiovascular Health ◽

Health Study ◽

Cardiovascular Health Study ◽

Incident Heart Failure

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Serum Individual Nonesterified Fatty Acids and Risk of Heart Failure in Older Adults

Cardiology ◽

10.1159/000513917 ◽

2021 ◽

pp. 1-8

Author(s):

Luc Djousse ◽

Mary L. Biggs ◽

Nirupa R. Matthan ◽

Joachim H. Ix ◽

Annette L. Fitzpatrick ◽

...

Keyword(s):

Heart Failure ◽

Older Adults ◽

Fatty Acids ◽

Cardiovascular Health ◽

Cox Regression ◽

Hormone Replacement ◽

Health Study ◽

Cardiovascular Health Study ◽

Nonesterified Fatty Acids

Background: Heart failure (HF) is highly prevalent among older adults and is associated with high costs. Although serum total nonesterified fatty acids (NEFAs) have been positively associated with HF risk, the contribution of each individual NEFA to HF risk has not been examined. Objective: The aim of this study was to examine the association of individual fasting NEFAs with HF risk in older adults. Methods: In this prospective cohort study of older adults, we measured 35 individual NEFAs in 2,140 participants of the Cardiovascular Health Study using gas chromatography. HF was ascertained using review of medical records by an endpoint committee. Results: The mean age was 77.7 ± 4.4 years, and 38.8% were male. During a median follow-up of 9.7 (maximum 19.0) years, 655 new cases of HF occurred. In a multivariable Cox regression model controlling for demographic and anthropometric variables, field center, education, serum albumin, glomerular filtration rate, physical activity, alcohol consumption, smoking, hormone replacement therapy, unintentional weight loss, and all other measured NEFAs, we observed inverse associations (HR [95% CI] per standard deviation) of nonesterified pentadecanoic (15:0) (0.73 [0.57–0.94]), γ-linolenic acid (GLA) (0.87 [0.75–1.00]), and docosahexaenoic acid (DHA) (0.73 [0.61–0.88]) acids with HF, and positive associations of nonesterified stearic (18:0) (1.30 [1.04–1.63]) and nervonic (24:1n-9) (1.17 [1.06–1.29]) acids with HF. Conclusion: Our data are consistent with a higher risk of HF with nonesterified stearic and nervonic acids and a lower risk with nonesterified 15:0, GLA, and DHA in older adults. If confirmed in other studies, specific NEFAs may provide new targets for HF prevention.

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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 ◽

10.1161/circ.137.suppl_1.p039 ◽

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.

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