Kidney Week

Abstract: SA-PO528

Evaluation of Plasma Sphingolipids as Mediators of the Relationship Between Kidney Diseases and Cardiovascular Events

Session Information

• Hypertension and CVD: Clinical - II
  November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1602 Hypertension and CVD: Clinical

Authors

• Lidgard, Benjamin, University of Washington, Seattle, Washington, United States

Benjamin Lidgard,

• Bansal, Nisha, University of Washington, Seattle, Washington, United States

Nisha Bansal,

• Zelnick, Leila R., University of Washington, Seattle, Washington, United States

Leila R. Zelnick,

• Hoofnagle, Andrew N., University of Washington, Seattle, Washington, United States

Andrew N. Hoofnagle,

• Fretts, Amanda M., University of Washington, Seattle, Washington, United States

Amanda M. Fretts,

• Longstreth, W. T., University of Washington, Seattle, Washington, United States

W. T. Longstreth,

• Shlipak, Michael, San Francisco VA Health Care System, San Francisco, California, United States

Michael Shlipak,

• Umans, Jason G., Georgetown University, Washington, District of Columbia, United States

Jason G. Umans,

• Lemaitre, Rozenn, University of Washington, Seattle, Washington, United States

Rozenn Lemaitre,

Background

Patients with chronic kidney disease (CKD) are at higher risk for cardiovascular events. Sphingolipids are a family of circulating lipids with regulatory and signaling roles that are strongly associated with both eGFR and cardiovascular disease. We examined whether circulating sphingolipids partially mediate the associations between eGFR and cardiovascular events.

Methods

We measured the circulating concentrations of 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 the 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 draws, using a Bonferroni-corrected p value for significance of 0.00625.

Results

The mean (±SD) eGFR was 70 (±16) mL/min/1.73 m², and the mean age was 76 (±5) years. Lower eGFR was associated with higher plasma ceramide 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 strongest mediators were ceramide-16:0 (proportion mediated 14%, 95% CI 8-23%) and sphingomyelin-16:0 (proportion mediated 10%, 95% CI 5-17%). No sphingolipids significantly mediated the association between eGFR and ischemic stroke (Table).

Conclusion

Plasma sphingolipids partially mediated the association between lower eGFR and incident heart failure. Altered sphingolipids metabolism may contribute to heart failure in patients with CKD.

Funding

• NIDDK Support