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.

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.

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 Fatty acid-binding protein 4 and incident heart failure: the Cardiovascular Health Study

2013 ◽  
Vol 15 (4) ◽  
pp. 394-399 ◽  
Author(s):  
Luc Djoussé ◽  
Traci M. Bartz ◽  
Joachim H. Ix ◽  
Jinesh Kochar ◽  
Jorge R. Kizer ◽  
...  
Keyword(s):  
Heart Failure ◽  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Cardiovascular Health ◽  
Binding Protein ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Incident Heart Failure

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.

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 5011: Role of Autonomic Nervous System Dysregulation and Inflammation in the Increased Risk of Depression for Cardiovascular Mortality: The Cardiovascular Health Study

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Willem J Kop ◽  
Phyllis K Stein ◽  
Joshua I Barzilay ◽  
Russell P Tracy ◽  
John S Gottdiener
Keyword(s):  
Nervous System ◽  
Autonomic Nervous System ◽  
Cardiovascular Mortality ◽  
Inflammatory Markers ◽  
Cardiovascular Health ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Scaling Exponent ◽  
Autonomic Nervous

The increased cardiovascular (CV) risk associated with depression is hypothesized to be explained by autonomic nervous system (ANS) dysregulation and inflammatory processes. This study determines the role of ANS dysregulation and inflammation in the predictive value of depression for CV mortality. 908 participants of the Cardiovascular Health Study (age 71±5 yrs) free of CV disease were evaluated for depression (CES-D scale), ANS dysregulation by abnormal non-linear heart rate variability (decreased short-term fractal scaling exponent), and inflammation (IL-6, CRP, fibrinogen and WBC). Predictors of CV mortality were examined using Cox regression analysis, adjusting for age, sex, race, systolic blood pressure, diabetes, subclinical disease, use of beta-blockers, smoking status, BMI, and physical activity (median follow-up=13.3 yrs). Risks were calculated for subgroups based on the presence or absence of depression, and ANS or inflammatory CV risk factors (Figure ). Depression was predictive of CV mortality (RR=1.88, CI=1.23–2.86), ANS dysregulation (p=0.014) and inflammatory markers (IL-6 p=0.072; WBC p=0.033; and fibrinogen p=0.050) were correlated with depression. The association of depression with CV mortality occurred primarily in the presence of ANS dysregulation and/or inflammation (Figure ). Addition of ANS and inflammatory markers to the multivariate model did not substantially reduce the CV mortality risk of depression (adjusted RR=1.65, CI=1.03–2.65). Depression is predictive of cardiovascular mortality, and the elevated risk is additive to autonomic nervous system dysregulation and inflammation

Abstract P122: Plasma Fatty Acid Binding Protein 4 is Associated with the Incidence of Sudden Cardiac Death in Non-Diabetic Adults in the Cardiovascular Health Study

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Luc Djousse ◽  
Marlena Maziarz ◽  
Mary L Biggs ◽  
Joachim H Ix ◽  
Jorge R Kizer ◽  
...  
Keyword(s):  
Older Adults ◽  
Fatty Acid ◽  
Cardiac Death ◽  
Fatty Acid Binding Protein ◽  
Cardiovascular Health ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Diabetes Status

Background: Fatty acid binding protein 4 (FABP4) is an adipokine that plays a role in lipid transport. Previous studies have reported that FABP4 may increase the risk of diabetes and exert negative inotropy on the myocardium. It is unknown whether plasma FABP4 is associated with the risk of sudden cardiac death (SCD). Objective: To test the hypothesis that plasma FABP4 is associated with a higher incidence of SCD in older adults and determine if diabetes status modifies this association. Methods: We prospectively analyzed data on 4,564 men and women aged 65+ years from the Cardiovascular Health Study. FABP4 was measured at baseline using ELISA and SCD events were adjudicated through review of medical records (inter-reviewer agreement of 88% and kappa of 0.74). We used Cox proportional hazards model to examine the association between FABP4 and SCD. Results: During a median follow up of 11.8 years, 146 new cases of SCD occurred. In a multivariable model adjusting for age, sex, race, clinic, education, glomerular filtration rate based on cystatin C, high-sensitive C-reactive protein, leisure time physical activity, hormone replacement therapy, alcohol intake, self-reported general health status, smoking, prevalent coronary heart disease, and prevalent heart failure, each higher standard deviation (SD) of plasma FABP4 was associated with a non-significant 14% (95% CI: -5% to 37%) higher risk of SCD. When stratified by prevalent diabetes status, FABP4 was associated with a higher risk of SCD in non-diabetic participants, [HR per SD of FABP4: 1.37 (95% CI: 1.11-1.67)] but not in diabetic participants [HR per SD of FABP4: 0.77 (95% CI: 0.52-1.15)], p for diabetes-FABP4 interaction was 0.026. Conclusion: A single measure of plasma FABP4 obtained later in life was associated with a higher risk of SCD among older adults without diabetes but not among those with diabetes. If confirmed in other studies, these data may point to novel mechanisms and opportunities for SCD prevention.

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