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

TitleCirculating Ceramides and Sphingomyelins and Risk of Mortality: The Cardiovascular Health Study.
Publication TypeJournal Article
Year of Publication2021
AuthorsFretts, AM, Jensen, PN, Hoofnagle, AN, McKnight, B, Sitlani, CM, Siscovick, DS, King, IB, Psaty, BM, Sotoodehnia, N, Lemaitre, RN
JournalClin Chem
Date Published2021 Nov 26
Abstract<p><b>BACKGROUND: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p>
Alternate JournalClin Chem
PubMed ID34580702
PubMed Central IDPMC8634404
Grant ListHHSN268201200036C / DK / NIDDK NIH HHS / United States
/ / National Institute of Aging /
U01 HL130114 / HL / NHLBI NIH HHS / United States
R01AG023629 / NS / NINDS NIH HHS / United States
R01 HL128575 / HL / NHLBI NIH HHS / United States
P30 DK035816 / DK / NIDDK NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
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