03876nas a2200397 4500008004100000022001400041245010100055210006900156260001600225300001300241490000600254520276700260653000903027653001403036653001903050653002703069653002103096653001603117653001103133653001103144653000903155653001803164653001903182100001903201700002003220700002203240700002503262700002203287700002403309700002403333700001903357700002003376700002203396700002403418856003603442 2023 eng d a2574-380500aPlasma Ceramides and Sphingomyelins and Sudden Cardiac Death in the Cardiovascular Health Study.0 aPlasma Ceramides and Sphingomyelins and Sudden Cardiac Death in  c2023 Nov 01 ae23438540 v63 a

IMPORTANCE: Sphingolipids, including ceramides and sphingomyelins, may influence the pathophysiology and risk of sudden cardiac death (SCD) through multiple biological activities. Whether the length of the fatty acid acylated to plasma sphingolipid species is associated with SCD risk is not known.

OBJECTIVE: To determine whether the saturated fatty acid length of plasma ceramides and sphingomyelins influences the association with SCD risk.

DESIGN, SETTING, AND PARTICIPANTS: In this 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. Baseline data were collected from January 1992 to December 1995 during annual examinations. Data were analyzed from February 11, 2020, to September 9, 2023.

EXPOSURES: Eight plasma sphingolipid species (4 ceramides and 4 sphingomyelins) with saturated fatty acids of 16, 20, 22, and 24 carbons.

MAIN OUTCOME AND MEASURE: Association of plasma ceramides and sphingomyelins with saturated fatty acids of different lengths with SCD risk.

RESULTS: Among the 4612 CHS participants included in the analysis (mean [SD] age, 77 [5] years; 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, 1.34 [95% CI, 1.12-1.59]; HR for SM-16, 1.37 [95% CI, 1.12-1.67]). 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, 1.06 [95% CI, 0.90-1.24]; HR for ceramide with behenic acid, 0.92 [95% CI, 0.77-1.10]; HR for ceramide with lignoceric acid, 0.92 [95% CI, 0.77-1.09]; HR for sphingomyelin with arachidic acid, 0.83 [95% CI, 0.71-0.98]; HR for sphingomyelin with behenic acid, 0.84 [95% CI, 0.70-1.00]; HR for sphingomyelin with lignoceric acid, 0.86 [95% CI, 0.72-1.03]).

CONCLUSIONS AND RELEVANCE: 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.

10aAged10aCeramides10aCohort Studies10aDeath, Sudden, Cardiac10aEicosanoic Acids10aFatty Acids10aFemale10aHumans10aMale10aSphingolipids10aSphingomyelins1 aBockus, Lee, B1 aJensen, Paul, N1 aFretts, Amanda, M1 aHoofnagle, Andrew, N1 aMcKnight, Barbara1 aSitlani, Colleen, M1 aSiscovick, David, S1 aKing, Irena, B1 aPsaty, Bruce, M1 aSotoodehnia, Nona1 aLemaitre, Rozenn, N uhttps://chs-nhlbi.org/node/9533