Abstract P044: Plasma Phospholipid Very Long Chain Saturated Fatty Acids and Healthy Aging in Older Adults: The Cardiovascular Health Study

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Rozenn N Lemaitre ◽  
Mary L Biggs ◽  
Barbara McKnight ◽  
Heidi T Lai ◽  
Xiaoling Song ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Lower Risk ◽  
Healthy Aging ◽  
Cardiovascular Health ◽  
Biological Activities ◽  
Saturated Fatty Acids ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Long Chain

Introduction: Circulating very long-chain saturated fatty acids (VLSFA) are biomarkers of diet and metabolism which impart different biological activities to sphingolipids and may influence physiological pathways relevant to aging. Higher levels of circulating VLSFAs have been associated with lower risk of all-cause mortality, cardiovascular outcomes, and diabetes. Apart from these associations, it is unknown whether these biomarkers are related to the maintenance of healthy aging. Hypothesis: Higher levels of circulating VLSFA are associated with lower risk of unhealthy aging. Methods: Phospholipid fatty acids were measured in serial plasma samples collected among participants of the Cardiovascular Health Study (CHS) in 1992-93, 1998-99, and 2005-06. Incident unhealthy aging was defined as the onset of cardiovascular disease (CVD), cancer, lung disease, severe chronic kidney disease, ≥1 difficulties with activities of daily living (ADL), or reduced cognitive function (Mini-Mental State Examination<80). We assessed the associations of arachidic acid (20:0), behenic acid (22:0) and lignoceric acid (24:0), with risk of incident unhealthy aging using Cox regression with time-updated fatty acid levels and covariates. Results: Among 2,183 CHS participants with one or more fatty acid measure and healthy aging up to the time of their first VLSFA measurement, mean age at baseline was 75 years, 62% were female, and 12% were black. During median follow-up of 8 years, all but 198 participants failed to age successfully. The most common conditions marking the first occurrence of unhealthy aging were ADL difficulties and CVD (27% each). In analyses adjusted for major risk factors, higher levels of 22:0 and 24:0 were associated with lower risk of unhealthy aging (Table). Conclusions: Higher levels of two circulating VLSFA, 22:0 and 24:0, are associated with lower risk of unhealthy aging. These findings open a new avenue of research into these saturated fatty acids and their possible beneficial role in promoting better aging.

Circulating Ceramides and Sphingomyelins and Risk of Mortality: The Cardiovascular Health Study

2021 ◽  
Author(s):  
Amanda M Fretts ◽  
Paul N Jensen ◽  
Andrew N Hoofnagle ◽  
Barbara McKnight ◽  
Colleen M Sitlani ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Cardiovascular Health ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Risk Of Death ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
High Concentrations ◽  
Long Chain

Abstract Background Recent studies suggest that associations of ceramides (Cer) and sphingomyelins (SM) with health outcomes differ according to the fatty acid acylated to the sphingoid backbone. The purpose of this study was to assess associations of Cer and SM species with mortality. Methods The study population included participants from the Cardiovascular Health Study (CHS), a community-based cohort of adults aged ≥65 years who were followed from 1992–2015 (n = 4612). Associations of plasma Cer and SM species carrying long-chain (i.e., 16:0) and very-long-chain (i.e., 20:0, 22:0, 24:0) saturated fatty acids with mortality were assessed using Cox proportional hazards models. Results During a median follow-up of 10.2 years, 4099 deaths occurred. High concentrations of Cer and SM carrying fatty acid 16:0 were each associated with an increased risk of mortality. Conversely, high concentrations of several ceramide and sphingomyelin species carrying longer fatty acids were each associated with a decreased risk of mortality. The hazard ratios for total mortality per 2-fold difference in each Cer and SM species were: 1.89 (95% CI), 1.65–2.17 for Cer-16, 0.79 (95% CI, 0.70–0.88) for Cer-22, 0.74 (95% CI, 0.65–0.84) for Cer-24, 2.51 (95% CI, 2.01–3.14) for SM-16, 0.68 (95% CI, 0.58–0.79) for SM-20, 0.57 (95% CI, 0.49–0.67) for SM-22, and 0.66 (0.57–0.75) for SM-24. We found no association of Cer-20 with risk of death. Conclusions Associations of Cer and SM with the risk of death differ according to the length of their acylated saturated fatty acid. Future studies are needed to explore mechanisms underlying these relationships.

Abstract MP03: Plasma Sphingolipids and Risks of Heart Failure and Atrial Fibrillation in Older Adults: The Cardiovascular Health Study

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Rozenn N Lemaitre ◽  
Paul N Jensen ◽  
Barbara McKnight ◽  
Andrew Hoofnagle ◽  
Irena B King ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Fatty Acid ◽  
Lower Risk ◽  
Cardiovascular Health ◽  
Biological Activities ◽  
Experimental Studies ◽  
Health Study ◽  
Cardiovascular Health Study

Introduction: Ceramides and sphingomyelins (sphingolipids) are circulating lipids involved in multiple physiological pathways relevant to heart failure (HF) and atrial fibrillation (AF), including apoptosis, oxidative stress, and inflammation. Experimental studies suggest that sphingolipids with different saturated fatty acids exhibit different biological activities, but their relationships with HF and AF are unknown. Hypothesis: Higher levels of plasma ceramide and sphingomyelin that contain the fatty acid 16:0 are associated with higher risks of HF and AF; and higher levels of ceramides and sphingomyelins that contain the fatty acid 20:0, 22:0 or 24:0 are associated with lower risks. Methods: We measured sphingolipids in the Cardiovascular Health Study (CHS) in plasma samples from 1994-95 (N=4026) or from 1992-93 (N=586). We assessed the separate associations of the levels of 8 sphingolipids with risks of incident HF and incident AF using Cox regression. A p-value threshold of 0.006 was used to account for multiple testing. Results: Among 4,612 participants, 1179 incident HF and 1198 incident AF occurred during >40,000 person-years of follow-up. In adjusted analyses, higher levels of Cer-16 (ceramide with 16:0) and SM-16 (sphingomyelin with 16:0) were associated with higher risk of incident HF, but not with risk of incident AF (Table). In contrast, higher levels of Cer-20, Cer-22 and Cer-24 were each associated with lower risk of AF, but not with risk of HF. Higher levels of SM-20, SM-22, and SM-24 tended to be associated with lower risks of AF and HF, with only the association of SM-20 with AF significant. Conclusions: Plasma levels of ceramide and sphingomyelin with 16:0 show different associations with HF and AF than species with 20:0, 22:0 or 24:0. Associations of Cer-16 and SM-16 specifically with higher risk of HF may be due to a role of apoptosis in HF. The novel findings that Cer-20, Cer-22, and Cer-24 are associated with lower risk of AF warrant further examination of the role of these sphingolipids in protecting from AF.

scholarly journals Plasma Ceramides and Sphingomyelins in Relation to Atrial Fibrillation Risk: The Cardiovascular Health Study

2020 ◽  
Vol 9 (4) ◽  
Author(s):  
Paul N. Jensen ◽  
Amanda M. Fretts ◽  
Andrew N. Hoofnagle ◽  
Colleen M. Sitlani ◽  
Barbara McKnight ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Fatty Acids ◽  
Palmitic Acid ◽  
Cardiovascular Health ◽  
Saturated Fatty Acids ◽  
Behenic Acid ◽  
Hazard Ratio ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Long Chain

Background Ceramides exhibit multiple biological activities that may influence the pathophysiological characteristics of atrial fibrillation (AF). Whether the length of the saturated fatty acid carried by the ceramide or their sphingomyelin precursors are associated with AF risk is not known. Methods and Results Among 4206 CHS (Cardiovascular Health Study) participants (mean age, 76 years; 40% men) who were free of prevalent AF at baseline, we identified 1198 incident AF cases over a median 8.7 years of follow‐up. We examined 8 sphingolipid species: ceramide and sphingomyelin species with palmitic acid and species with very‐long‐chain saturated fatty acids: arachidic; behenic; and lignoceric. In adjusted Cox regression analyses, ceramides and sphingomyelins with very‐long‐chain saturated fatty acids were associated with reduced AF risk (ie, per 2‐fold higher ceramide with behenic acid hazard ratio, 0.71; 95% CI, 0.59–0.86; sphingomyelin with behenic acid hazard ratio, 0.60; 95% CI, 0.46–0.77). In contrast, ceramides and sphingomyelins with palmitic acid were associated with increased AF risk (ceramide with palmitic acid hazard ratio, 1.31; 95% CI, 1.03–1.66; sphingomyelin with palmitic acid hazard ratio, 1.73; 95% CI, 1.18–2.55). Associations were attenuated with adjustment for NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), but did not differ significantly by age, sex, race, body mass index, or history of coronary heart disease. Conclusions Our findings suggest that several ceramide and sphingomyelin species are associated with incident AF, and that these associations differ on the basis of the fatty acid. Ceramides and sphingomyelins with palmitic acid were associated with increased AF risk, whereas ceramides and sphingomyelins with very‐long‐chain saturated fatty acids were associated with reduced AF risk.

scholarly journals Circulating Very Long‐Chain Saturated Fatty Acids and Heart Failure: The Cardiovascular Health Study

2018 ◽  
Vol 7 (21) ◽  
Author(s):  
Rozenn N. Lemaitre ◽  
Barbara McKnight ◽  
Nona Sotoodehnia ◽  
Amanda M. Fretts ◽  
Waqas T. Qureshi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Fatty Acids ◽  
Cardiovascular Health ◽  
Saturated Fatty Acids ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Long Chain

Abstract P001: Plasma Phospholipid Saturated Fatty Acids and Incident Atrial Fibrillation: the Cardiovascular Health Study

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Amanda M Fretts ◽  
Dariush Mozaffarian ◽  
David S Siscovick ◽  
Luc Djousse ◽  
Susan R Heckbert ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Fatty Acids ◽  
Cardiovascular Health ◽  
Cox Regression ◽  
Biological Activities ◽  
Saturated Fatty Acids ◽  
Membrane Properties ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Lipid Species

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 (SFA) with risk of AF. SFAs of different length differ in dietary and metabolic origin, incorporation into membrane lipid species, membrane properties, and biological activities that may influence the pathophysiology of AF. Moreover, both diet and metabolic pathways are determinants of circulating SFAs. Methods: The study population included 2,899 participants from the Cardiovascular Health Study, a community-based longitudinal cohort of adults aged 65 years or older, free of prevalent coronary heart disease and AF. 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. Results: During 29,864 person-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 to lowest quartiles: 1.48. 95% CI: 1.18, 1.86). On the other hand, 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 versus bottom quartile were 0.76 (0.61, 0.95) for 18:0; 0.78 (0.63, 0.97) for 20:0; 0.62 (0.50, 0.78) for 22:0; and 0.68 (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.

scholarly journals Plasma phospholipid very-long-chain saturated fatty acids and incident diabetes in older adults: the Cardiovascular Health Study

2015 ◽  
Vol 101 (5) ◽  
pp. 1047-1054 ◽  
Author(s):  
Rozenn N Lemaitre ◽  
Amanda M Fretts ◽  
Colleen M Sitlani ◽  
Mary L Biggs ◽  
Kenneth Mukamal ◽  
...  
Keyword(s):  
Older Adults ◽  
Fatty Acids ◽  
Cardiovascular Health ◽  
Saturated Fatty Acids ◽  
Plasma Phospholipid ◽  
Incident Diabetes ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Long Chain

Association Between Erythrocyte Levels of n-3 Polyunsaturated Fatty Acids and Risk of Frailty in Community-Dwelling Older Adults: The Korean Frailty and Aging Cohort Study

2020 ◽  
Author(s):  
Doyeon Kim ◽  
Chang Won Won ◽  
Yongsoon Park
Keyword(s):  
Fatty Acids ◽  
Cohort Study ◽  
Polyunsaturated Fatty Acids ◽  
Cardiovascular Health ◽  
Community Dwelling ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Cross Sectional ◽  
Frailty Criterion ◽  
Long Chain

Abstract Background Inflammation is a major risk factor for frailty, but n-3 polyunsaturated fatty acids (PUFA) has been suggested as an anti-inflammatory agent. The present study aimed to investigate the hypothesis that the higher erythrocyte levels of long-chain n-3 PUFA were associated with lower odds of frailty and frailty criterion. Methods Cross-sectional analysis from the Korean Frailty and Aging Cohort Study, a total of 1,435 people aged 70–84 years were included. Sex- and age-stratified community residents, drawn in urban and rural regions nationwide, were eligible for participation in the study. All participants were categorized as frail and nonfrail according to the Cardiovascular Health Study index. Results The likelihood of frailty was inversely associated with the erythrocyte levels of eicosapentaenoic acid (EPA; odds ratio [OR] per unit 0.33; 95% confidence interval [CI] 0.14–0.77; p for trend = .002) and docosahexaenoic acid (DHA; OR per unit 0.42; 95% CI 0.20–0.87; p for trend = .018). Among each frailty criterion, the likelihood of slow walking speed was associated with erythrocyte levels of EPA and DHA, and the likelihood of exhaustion was inversely associated with the erythrocyte levels of DHA. Conclusions The present study showed that the frailty and frailty criterion were significantly associated with lower erythrocyte levels of long-chain n-3 PUFA, suggesting that lower n-3 PUFA could be a marker for the risk of frailty.

Abstract P492: Circulating Sphingolipids and Risk of Mortality: The Cardiovascular Health Study

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Amanda M Fretts ◽  
Paul Jensen ◽  
Andrew Hoofnagle ◽  
Barbara McKnight ◽  
Colleen Sitlani ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Saturated Fatty Acid ◽  
Lower Risk ◽  
Cardiovascular Health ◽  
Lipid Lowering ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Risk Of Death ◽  
Risk Of Mortality ◽  
Lipid Species

Introduction: Recent studies suggest that the type of saturated fatty acid bound to sphingolipids influences sphingolipid activity, and that associations of ceramides (Cer) and sphingomyelins (SM) with cardiovascular outcomes may differ by lipid species. The purpose of this study was to assess associations of Cer and SM species with mortality among 4,612 older adults from the Cardiovascular Health Study, a population-based prospective study of adults aged ≥65 y who were followed from 1992-2015. Hypothesis: Higher levels of circulating Cer and SM with palmitic acid (Cer-16) are associated with a higher risk of mortality (i.e., deaths from cardiovascular disease (CVD) and non-cardiovascular causes) while higher levels of Cer and SM with very-long chain saturated fatty acids arachidic acid (Cer-20 and SM-20), behenic acid (Cer-22 and SM-22), and lignoceric acid (Cer-24 and SM-24) are associated with a lower risk. Methods: The associations of each sphingolipid with mortality were assessed using Cox proportional hazards models. Models adjusted for age, sex, self-reported race, geographic area, education, smoking, alcohol use, BMI, activities of daily living, HDL and LDL cholesterol, triglycerides, systolic blood pressure, physical activity, use of hypertension or lipid-lowering drugs, self-reported health status, prevalent diabetes, CVD, heart failure (HF), and other sphingolipids species. Results: During a median follow-up of 10.2 years (range 0-23 years), 4,099 deaths occurred. At each time, higher levels of Cer-16 and SM-16 were associated with a higher risk of mortality, while higher levels of Cer-22, Cer-24, SM-20, SM-22, and SM-24 were associated with a lower risk of mortality (Figure). Models that did not adjust for diabetes, CVD, and HF produced similar results. Conclusions: These findings suggest that the associations of Cer and SM with the risk of death differ according to the length of their acylated saturated fatty acid, and support the need for future studies to explore mechanisms underlying these relations.

scholarly journals Plasma Phospholipid Saturated Fatty Acids and Incident Atrial Fibrillation: The Cardiovascular Health Study

2014 ◽  
Vol 3 (3) ◽  
Author(s):  
Amanda M. Fretts ◽  
Dariush Mozaffarian ◽  
David S. Siscovick ◽  
Luc Djousse ◽  
Susan R. Heckbert ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Fatty Acids ◽  
Cardiovascular Health ◽  
Saturated Fatty Acids ◽  
Plasma Phospholipid ◽  
Health Study ◽  
Cardiovascular Health Study

Abstract MP14: Long-chain Monounsaturated Fatty Acids and Incidence of Coronary Heart Disease: The Cardiovascular Health Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Fumiaki Imamura ◽  
Rozenn N Lemaitre ◽  
Irena King ◽  
Xiaoling Song ◽  
David S Siscovick ◽  
...  
Keyword(s):  
Risk Factors ◽  
Fatty Acids ◽  
Cardiovascular Health ◽  
Plasma Phospholipid ◽  
Monounsaturated Fatty Acids ◽  
Cox Proportional Hazards ◽  
Baseline Risk ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Long Chain

Background: Decades-old animal experiments demonstrated that consumption of large amounts of long-chain monounsaturated fatty acids (LCMUFA, 22:1 and 24:1 fatty acids) caused cardiotoxicity. We recently found that plasma phospholipid 22:1 and 24:1 were associated with higher incidence of congestive heart failure (CHF) in two independent cohorts: the Cardiovascular Health Study (CHS) and the Atherosclerosis Risk in Communities Study. However, their association with incident CHD is unknown. Aim: to investigate association of plasma phospholipid 22:1 and 24:1 levels with incident CHD. Methods: The study included 3,221 adults free of CHD (age=74.9±5.2) in CHS in whom plasma phospholipid LCMUFA were measured in 1992. Incident CHD events from 1992 to 2006 were centrally adjudicated, and we assessed total CHD, including fatal CHD (fatal MI and other CHD deaths) and non-fatal MI. We examined prospective associations of LCMUFA with incident CHD using Cox proportional hazards. We further evaluated potential confounding or mediation by baseline risk factors and incident CHF. Results: Mean±SD phospholipid levels of 22:1 and 24:1 were 0.03±0.01 and 1.96±0.44 percent of total fatty acids. During 34,776 person-years, 628 incident CHD events occurred, including 309 fatal CHD and 401 non-fatal MIs. After multivariable adjustment, higher levels of both 22:1 and 24:1 were associated with higher risk of total incident CHD. Hazard ratios (95% CI) for quintiles 5 vs. 1 of 22:1 and 24:1 levels were 1.48 (1.07-2.06, p trend=0.005) and 1.65 (1.16-2.34, p trend=0.001). The associations with CHD were largely specific to fatal CHD rather than non-fatal MI (Figure). These associations did not change after adjustment for incident CHF and baseline risk factors including circulating lipids, blood pressure, and inflammatory markers. Conclusions: Higher levels of circulating 22:1 and 24:1 LCMUFA were associated with higher incidence of CHD, in particular fatal CHD, supporting the possibility of cardiotoxicity by current levels of LCMUFA exposure.

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