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.

scholarly journals Serial measures of circulating biomarkers of dairy fat and total and cause-specific mortality in older adults: the Cardiovascular Health Study

2018 ◽  
Vol 108 (3) ◽  
pp. 476-484 ◽  
Author(s):  
Marcia C de Oliveira Otto ◽  
Rozenn N Lemaitre ◽  
Xiaoling Song ◽  
Irena B King ◽  
David S Siscovick ◽  
...  
Keyword(s):  
Older Adults ◽  
Total Mortality ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Heptadecanoic Acid ◽  
Stroke Mortality ◽  
Dairy Fat ◽  
Specific Mortality ◽  
Cvd Mortality

ABSTRACT 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.

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 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 Fatty acids in the de novo lipogenesis pathway and risk of coronary heart disease: the Cardiovascular Health Study

2011 ◽  
Vol 94 (2) ◽  
pp. 431-438 ◽  
Author(s):  
Jason HY Wu ◽  
Rozenn N Lemaitre ◽  
Fumiaki Imamura ◽  
Irena B King ◽  
Xiaoling Song ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Cardiovascular Health ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Health Study ◽  
Cardiovascular Health Study

Abstract 20: Circulating Omega-6 Polyunsaturated Fatty Acids and Total and Cause-Specific Mortality: the Cardiovascular Health Study

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Jason H Wu ◽  
Rozenn Lemaitre ◽  
Irena King ◽  
Xiaoling Song ◽  
David Siscovick ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Linoleic Acid ◽  
Polyunsaturated Fatty Acids ◽  
Cardiovascular Health ◽  
Cox Regression ◽  
Total Mortality ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Specific Mortality ◽  
Omega 6

Background: While omega-6 polyunsaturated fatty acids (n-6 PUFA) have been recommended to reduce CHD, controversy remains about benefits vs. harms, including depending on types of n-6 PUFA and diseases examined. Aims: To assess associations of circulating n-6 PUFA including linoleic acid (LA, the major dietary PUFA), Γ-linoleic acid (GLA), dihomo-Γ-linoleic acid (DGLA), and arachidonic acid (AA),with incident total and cause-specific mortality in the Cardiovascular Health Study (CHS), a community-based US cohort. Methods: Among 2,692 participants age≥65y and free of CVD at baseline, plasma phospholipid n-6 PUFA were measured at baseline using standardized methods. All-cause and cause-specific mortality, and total (fatal or nonfatal) incident CHD and stroke, were assessed and adjudicated centrally. Associations of PUFA biomarkers with risk were assessed by multivariable Cox regression. Results: During 33,091 person-years of follow-up (1992-2010), 1920 deaths occurred (including 660 cardiovascular deaths), as well as 414 fatal and 410 nonfatal CHD events, and 150 fatal and 384 nonfatal strokes. In multivariable models, higher LA was associated with lower risk of total mortality, with extreme quintile HR 0.84 (95% CI 0.71-0.98, P- trend 0.002). Lower death was largely attributable to CVD rather than non-CVD causes, especially nonarhythmic CHD mortality (HR 0.50, 95% CI 0.31-0.80, P- trend 0.001). Phospholipid GLA, DGLA, and AA levels were not associated with total or cause-specific mortality; e.g., for AA and CHD death, the extreme quintile HR was 0.98 (95% CI 0.71-1.37, P- trend 0.72). Evaluated semi-parametrically, LA showed graded (monotonic) inverse associations with total mortality ( Figure 1A ). There was little evidence that associations of n-6 PUFA with total mortality varied by age, sex, race, or plasma n-3 PUFA (Bonferroni corrected P =NS, Figure 1B ). Conclusion: Higher circulating LA, but not other n-6 PUFA, is inversely associated with total and CHD mortality in older adults.

scholarly journals CHANGES OVER TIME IN DAYTIME SLEEPINESS AMONG OLDER ADULTS RECEIVING LONG-TERM SERVICES AND SUPPORTS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S45-S46
Author(s):  
Darina V Petrovsky ◽  
Karen B Hirschman ◽  
Glenna Brewster ◽  
Alexandra L Hanlon ◽  
Liming Huang ◽  
...  
Keyword(s):  
Older Adults ◽  
Assisted Living ◽  
Daytime Sleepiness ◽  
Backward Elimination ◽  
Final Multivariable Model ◽  
Linear Regression Modeling ◽  
Services And Supports ◽  
Changes Over Time ◽  
Over Time

Abstract The purpose of this study was to examine the predictors of excessive daytime sleepiness (EDS) over the first two years of long-term services and supports (LTSS) for 470 older adults in assisted living communities (ALCs), nursing homes (NHs), or their homes. Mixed effects linear regression modeling using a backward elimination process was used to build a final multivariable model. In the final model, being female (p&lt;0.001) and fewer functional deficits (p&lt;0.001) at baseline were associated with decreases in EDS, while higher baseline measures of BMI (p=0.004) and number of symptoms (p&lt;0.001) were associated with higher EDS. Compared to older adults living in the community and receiving LTSS, those in NHs and ALCs had higher EDS (p&lt;0.001). Greater feelings of belonging and depressive symptoms at baseline were associated with slower rates of increase in EDS over time (both p&lt;0.001). Modifiable predictors of EDS and clinical implications will be discussed.

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