Title | Plasma Ceramides and Sphingomyelins in Relation to Heart Failure Risk. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Lemaitre, RN, Jensen, PN, Hoofnagle, A, McKnight, B, Fretts, AM, King, IB, Siscovick, DS, Psaty, BM, Heckbert, SR, Mozaffarian, D, Sotoodehnia, N |
Journal | Circ Heart Fail |
Volume | 12 |
Issue | 7 |
Pagination | e005708 |
Date Published | 2019 Jul |
ISSN | 1941-3297 |
Abstract | <p><b>BACKGROUND: </b>Ceramides exhibit multiple biological activities that may influence the pathophysiology of heart failure. These activities may be influenced by the saturated fatty acid carried by the ceramide (Cer). However, the associations of different circulating Cer species, and their sphingomyelin (SM) precursors, with heart failure have received limited attention.</p><p><b>METHODS AND RESULTS: </b>We studied the associations of plasma Cer and SM species with incident heart failure in the Cardiovascular Health Study. We examined 8 species: Cer and SM with palmitic acid (Cer-16 and SM-16), species with arachidic acid (Cer-20 and SM-20), species with behenic acid (Cer-22 and SM-22), and species with lignoceric acid (Cer-24 and SM-24). During a median follow-up of 9.4 years, we identified 1179 cases of incident heart failure among 4249 study participants. In Cox regression analyses adjusted for risk factors, higher levels of Cer-16 and SM-16 were associated with higher risk of incident heart failure (hazard ratio for one SD increase:1.25 [95% CI, 1.16-1.36] and 1.28 [1.18-1.40], respectively). In contrast, higher levels of Cer-22 were associated with lower risk of heart failure in multivariable analyses further adjusted for Cer-16 (hazard ratio, 0.85 [0.78-0.92]); and higher levels of SM-20, SM-22 and SM-24 were associated with lower risk of heart failure in analyses further adjusted for SM-16 (hazard ratios, 0.83 [0.77-0.90], 0.81 [0.75-0.88], and 0.83 [0.77-0.90], respectively). No statistically significant interactions with age, sex, black race, body mass index, or baseline coronary heart disease were detected. Similar associations were observed for heart failure with preserved (n=529) or reduced (n=348) ejection fraction.</p><p><b>CONCLUSIONS: </b>This study shows associations of higher plasma levels of Cer-16 and SM-16 with increased risk of heart failure and higher levels of Cer-22, SM-20, SM-22, and SM-24 with decreased risk of heart failure.</p><p><b>CLINICAL TRIAL REGISTRATION: </b>URL: https://www.clinicaltrials.gov . Unique identifier: NCT00005133.</p> |
DOI | 10.1161/CIRCHEARTFAILURE.118.005708 |
Alternate Journal | Circ Heart Fail |
PubMed ID | 31296099 |
PubMed Central ID | PMC6629465 |
Grant List | U01 HL080295 / HL / NHLBI NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States HHSN268201800001C / HL / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States R01 HL128575 / HL / NHLBI NIH HHS / United States |