Incident Atrial Fibrillation and Disability-Free Survival in the 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.

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

Journal of the American Heart Association ◽

10.1161/jaha.119.012853 ◽

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.

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Response to Letter Regarding Article, “Physical Activity and Incidence of Atrial Fibrillation in Older Adults: The Cardiovascular Health Study”

Circulation ◽

10.1161/circulationaha.108.830901 ◽

2009 ◽

Vol 119 (5) ◽

Author(s):

Dariush Mozaffarian ◽

Curt D. Furberg ◽

Bruce M. Psaty ◽

David Siscovick

Keyword(s):

Physical Activity ◽

Atrial Fibrillation ◽

Older Adults ◽

Cardiovascular Health ◽

Health Study ◽

Cardiovascular Health Study

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The impact of height on the risk of atrial fibrillation: the Cardiovascular Health Study

European Heart Journal ◽

10.1093/eurheartj/ehs301 ◽

2012 ◽

Vol 33 (21) ◽

pp. 2709-2717 ◽

Cited By ~ 57

Author(s):

Michael A. Rosenberg ◽

Kristen K. Patton ◽

Nona Sotoodehnia ◽

Maria G. Karas ◽

Jorge R. Kizer ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cardiovascular Health ◽

Health Study ◽

Cardiovascular Health Study ◽

The Impact

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Physical Activity and Incidence of Atrial Fibrillation in Older Adults: The Cardiovascular Health Study

Journal of Atrial Fibrillation ◽

10.4022/jafib.v1i1.391 ◽

2008 ◽

Vol 1 (3) ◽

Author(s):

Suneet Mittal

Keyword(s):

Physical Activity ◽

Atrial Fibrillation ◽

Older Adults ◽

Cardiovascular Health ◽

Health Study ◽

Cardiovascular Health Study

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Hospital and clinical care costs associated with atrial fibrillation for Medicare beneficiaries in the Cardiovascular Health Study and the Framingham Heart Study

SAGE Open Medicine ◽

10.1177/2050312118759444 ◽

2018 ◽

Vol 6 ◽

pp. 205031211875944 ◽

Cited By ~ 13

Author(s):

Joseph AC Delaney ◽

Xiaoyan Yin ◽

João Daniel Fontes ◽

Erin R Wallace ◽

Asheley Skinner ◽

...

Keyword(s):

Atrial Fibrillation ◽

Confidence Interval ◽

Framingham Heart Study ◽

Cardiovascular Health ◽

Health Study ◽

Cardiovascular Health Study ◽

Heart Study ◽

Care Costs ◽

Onset Atrial Fibrillation ◽

New Onset

Background: Atrial fibrillation is increasingly prevalent as the US population ages and is associated with significant morbidity and mortality. Care for patients with atrial fibrillation can be costly, US health care costs are comparatively high, and there are few cost estimates available that incorporate detailed measurement of comorbidities and their effects on costs. Methods and Results: In the Cardiovascular Health Study and the Framingham Heart Study, participants aged 65 years or older with newly diagnosed atrial fibrillation were matched on age and follow-up time to referents free of atrial fibrillation. The total clinical and hospital medical costs paid by Medicare Parts A and B (drug costs from Medicare Part D costs were not included) in the year prior to diagnosis (or matching) were compared with costs in the following year. Estimates were adjusted for other medical conditions and adjusted to 2009 dollars. In the Cardiovascular Health Study, 513 participants were diagnosed with new-onset atrial fibrillation and survived 30 days post-atrial fibrillation diagnosis, and 513 referents (as a control cohort) were identified, with a mean age of 77 years. In the Framingham Heart Study, we identified 336 participants diagnosed with atrial fibrillation, who survived 30 days post-atrial fibrillation diagnosis and matched these participants to 336 referents. We compared these new-onset atrial fibrillation participants with referents, using a difference in difference design to account for both time trends and differences between the two groups. The adjusted incremental cost for participants with atrial fibrillation, compared with referents, was US$18,060 (95% confidence interval: US$14,965–US$21,155) in the Cardiovascular Health Study and US$20,012 (95% confidence interval: US$15,057–US$24,966) in the Framingham Heart Study. The pooled estimate was US$18,601 (95% confidence interval: US$15,981–US$21,234). Conclusion: Atrial fibrillation was associated with increased costs in the year after diagnosis in two community-based cohorts, even after careful accounting for age, time period, and systematically measured comorbidities.

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