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Evaluation of plasma sphingolipids as mediators of the relationship between kidney disease and cardiovascular events.
Wednesday,2023-09-13 20:50 America/Los_Angeles — ecterry
| Title | Evaluation of plasma sphingolipids as mediators of the relationship between kidney disease and cardiovascular events. |
| Publication Type | Journal Article |
| Year of Publication | 2023 |
| Authors | Lidgard, B, Bansal, N, Zelnick, LR, Hoofnagle, AN, Fretts, AM, Longstreth, WT, Shlipak, MG, Siscovick, DS, Umans, JG, Lemaitre, RN |
| Journal | EBioMedicine |
| Volume | 95 |
| Pagination | 104765 |
| Date Published | 2023 Aug 24 |
| ISSN | 2352-3964 |
| Abstract | <p><b>BACKGROUND: </b>Sphingolipids are a family of circulating lipids with regulatory and signaling roles that are strongly associated with both eGFR and cardiovascular disease. Patients with chronic kidney disease (CKD) are at high risk for cardiovascular events, and have different plasma concentrations of certain plasma sphingolipids compared to patients with normal kidney function. We hypothesize that circulating sphingolipids partially mediate the associations between eGFR and cardiovascular events.</p><p><b>METHODS: </b>We measured the circulating concentrations of 8 sphingolipids, including 4 ceramides and 4 sphingomyelins with the fatty acids 16:0, 20:0, 22:0, and 24:0, in plasma from 3,463 participants in a population-based cohort (Cardiovascular Health Study) without prevalent cardiovascular disease. We tested the adjusted mediation effects by these sphingolipids of the associations between eGFR and incident cardiovascular disease via quasi-Bayesian Monte Carlo method with 2,000 simulations, using a Bonferroni correction for significance.</p><p><b>FINDINGS: </b>The mean (±SD) eGFR was 70 (±16) mL/min/1.73 m; 62% of participants were women. Lower eGFR was associated with higher plasma ceramide-16:0 and sphingomyelin-16:0, and lower ceramides and sphingomyelins-20:0 and -22:0. Lower eGFR was associated with risk of incident heart failure and ischemic stroke, but not myocardial infarction. Five of eight sphingolipids partially mediated the association between eGFR and heart failure. The sphingolipids associated with the greatest proportion mediated were ceramide-16:0 (proportion mediated 13%, 95% CI 8-22%) and sphingomyelin-16:0 (proportion mediated 10%, 95% CI 5-17%). No sphingolipids mediated the association between eGFR and ischemic stroke.</p><p><b>INTERPRETATION: </b>Plasma sphingolipids partially mediated the association between lower eGFR and incident heart failure. Altered sphingolipids metabolism may be a novel mechanism for heart failure in patients with CKD.</p><p><b>FUNDING: </b>This study was supported by T32 DK007467 and a KidneyCure Ben J. Lipps Research Fellowship (Dr. Lidgard). Sphingolipid measurements were supported by R01 HL128575 (Dr. Lemaitre) and R01 HL111375 (Dr. Hoofnagle) from the National Heart, Lung, and Blood Institute (NHLBI).</p> |
| DOI | 10.1016/j.ebiom.2023.104765 |
| Alternate Journal | EBioMedicine |
| PubMed ID | 37634384 |
| PubMed Central ID | PMC10474367 |
| Grant List | U01 HL080295 / 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 P30 DK035816 / DK / NIDDK NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States R01 HL111375 / HL / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States HHSN268201800001C / HL / NHLBI NIH HHS / United States 75N92021D00006 / HL / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States T32 DK007467 / DK / NIDDK 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 |
ePub date:
23/08