Sphingolipids with acetylated palmitic acid are associated with increased risk of sudden cardiac death

Sudden cardiac death (SCD) is a growing concern and sphingolipids, including ceramides and sphingomyelins, is known to influence the pathophysiology and risk of sudden cardiac death (SCD) through multiple biological activities.

Bioactive sphingolipids constitute a family of lipids, including sphingosine, ceramide, sphingosine-1-phosphate (S1P) and ceramide-1-phosphate. These molecules act on distinct protein targets, including kinases, phosphatases, lipases and other enzymes and membrane receptors, and they exert distinct cellular functions.

Sphingolipids with palmitic acid was associated with increased risk of SCD, whereas those containing very-long-chain saturated fatty acids are not. In the cohort study it was found that out of 215 SCD events in older people of 65 years , plasma ceramides and sphingomyelins with palmitic acid were associated with 34% and 37% higher SCD risk, respectively, per higher SD of log plasma levels according to a study in JAMA Network.

Researchers designed a cohort study, multivariable Cox proportional hazards regression models were used to examine the association of sphingolipid species with SCD risk. The study population included 4612 participants in the Cardiovascular Health Study followed up prospectively for a median of 10.2 (IQR, 5.5-11.6) years. Eight plasma sphingolipid species (4 ceramides and 4 sphingomyelins) with saturated fatty acids of 16, 20, 22, and 24 carbons were particularly looked. Association of plasma ceramides and sphingomyelins with saturated fatty acids of different lengths with SCD risk was evaluated.

The key findings of the study are

• Out of 4612 study participants included in the analysis 2724 [59.1%] women; 6 [0.1%] American Indian; 4 [0.1%] Asian; 718 [15.6%] Black; 3869 [83.9%] White, and 15 [0.3%] Other), 215 SCD cases were identified.

• In adjusted Cox proportional hazards regression analyses, plasma ceramides and sphingomyelins with palmitic acid (Cer-16 and SM-16) were associated with higher SCD risk per higher SD of log sphingolipid levels (hazard ratio [HR] for Cer-16 was 1.34 ; HR for SM-16, was 1.37 ).

• Associations did not differ by baseline age, sex, race, or body mass index. No significant association of SCD with sphingolipids with very-long-chain saturated fatty acids was observed after correction for multiple testing (HR for ceramide with arachidic acid, was 1.06.

• HR for ceramide with behenic acid, was 0.92; HR for ceramide with lignoceric acid was, 0.92 ; HR for sphingomyelin with arachidic acid, was 0.83 ; HR for sphingomyelin with behenic was acid 0.84 ; HR for sphingomyelin with lignoceric acid was 0.86.

Researchers concluded that “The findings of this large, population-based cohort study of SCD identified that higher plasma levels of Cer-16 and SM-16 were associated with higher risk of SCD. Future studies are needed to examine the underlying mechanism of these associations.”

Reference: Bockus LB, Jensen PN, Fretts AM, et al. Plasma Ceramides and Sphingomyelins and Sudden Cardiac Death in the Cardiovascular Health Study. JAMA Netw Open. 2023;6(11):e2343854. doi:10.1001/jamanetworkopen.2023.43854.