Evaluation of plasma sphingolipids as mediators of the relationship between kidney disease and cardiovascular eventsResearch in context
Summary: Background: 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 concentr...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396423003316 |
| _version_ | 1797736842585440256 |
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| author | Benjamin Lidgard Nisha Bansal Leila R. Zelnick Andrew N. Hoofnagle Amanda M. Fretts William T. Longstreth, Jr. Michael G. Shlipak David S. Siscovick Jason G. Umans Rozenn N. Lemaitre |
| author_facet | Benjamin Lidgard Nisha Bansal Leila R. Zelnick Andrew N. Hoofnagle Amanda M. Fretts William T. Longstreth, Jr. Michael G. Shlipak David S. Siscovick Jason G. Umans Rozenn N. Lemaitre |
| author_sort | Benjamin Lidgard |
| collection | DOAJ |
| description | Summary: Background: 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. Methods: 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. Findings: The mean (±SD) eGFR was 70 (±16) mL/min/1.73 m2; 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. Interpretation: 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. Funding: 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). |
| first_indexed | 2024-03-12T13:19:46Z |
| format | Article |
| id | doaj.art-c8863ab2b9c6472a93ed61fcec604af9 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-03-12T13:19:46Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-c8863ab2b9c6472a93ed61fcec604af92023-08-26T04:43:36ZengElsevierEBioMedicine2352-39642023-09-0195104765Evaluation of plasma sphingolipids as mediators of the relationship between kidney disease and cardiovascular eventsResearch in contextBenjamin Lidgard0Nisha Bansal1Leila R. Zelnick2Andrew N. Hoofnagle3Amanda M. Fretts4William T. Longstreth, Jr.5Michael G. Shlipak6David S. Siscovick7Jason G. Umans8Rozenn N. Lemaitre9Department of Medicine, University of Washington, United States; Corresponding author. Kidney Research Institute, University of Washington, 908 Jefferson St, 3rd floor, Seattle, WA 98104, United States.Department of Medicine, University of Washington, United StatesDepartment of Medicine, University of Washington, United StatesDepartment of Medicine, University of Washington, United StatesDepartment of Medicine, University of Washington, United StatesDepartment of Medicine, University of Washington, United StatesKidney Health Research Collaborative, San Francisco Veterans Affairs Healthcare System and University of California San Francisco, United StatesNew York Academy of Medicine, United StatesGeorgetown University, United StatesDepartment of Medicine, University of Washington, United StatesSummary: Background: 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. Methods: 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. Findings: The mean (±SD) eGFR was 70 (±16) mL/min/1.73 m2; 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. Interpretation: 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. Funding: 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).http://www.sciencedirect.com/science/article/pii/S2352396423003316SphingolipidsCeramideSphingomyelinCKDHeart failureMediation |
| spellingShingle | Benjamin Lidgard Nisha Bansal Leila R. Zelnick Andrew N. Hoofnagle Amanda M. Fretts William T. Longstreth, Jr. Michael G. Shlipak David S. Siscovick Jason G. Umans Rozenn N. Lemaitre Evaluation of plasma sphingolipids as mediators of the relationship between kidney disease and cardiovascular eventsResearch in context EBioMedicine Sphingolipids Ceramide Sphingomyelin CKD Heart failure Mediation |
| title | Evaluation of plasma sphingolipids as mediators of the relationship between kidney disease and cardiovascular eventsResearch in context |
| title_full | Evaluation of plasma sphingolipids as mediators of the relationship between kidney disease and cardiovascular eventsResearch in context |
| title_fullStr | Evaluation of plasma sphingolipids as mediators of the relationship between kidney disease and cardiovascular eventsResearch in context |
| title_full_unstemmed | Evaluation of plasma sphingolipids as mediators of the relationship between kidney disease and cardiovascular eventsResearch in context |
| title_short | Evaluation of plasma sphingolipids as mediators of the relationship between kidney disease and cardiovascular eventsResearch in context |
| title_sort | evaluation of plasma sphingolipids as mediators of the relationship between kidney disease and cardiovascular eventsresearch in context |
| topic | Sphingolipids Ceramide Sphingomyelin CKD Heart failure Mediation |
| url | http://www.sciencedirect.com/science/article/pii/S2352396423003316 |
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