Background
Ceramides exhibit multiple biological activities that may influence the pathophysiological characteristics of
atrial fibrillation (AF). Whether the length of the
saturated fatty acid carried by the
ceramide or their
sphingomyelin precursors are associated with AF risk is not known. Methods and Results Among 4206 CHS (Cardiovascular Health Study) participants (mean age, 76 years; 40% men) who were free of prevalent AF at baseline, we identified 1198 incident AF cases over a median 8.7 years of follow-up. We examined 8
sphingolipid species:
ceramide and
sphingomyelin species with
palmitic acid and species with very-long-chain
saturated fatty acids: arachidic; behenic; and lignoceric. In adjusted Cox regression analyses,
ceramides and
sphingomyelins with very-long-chain
saturated fatty acids were associated with reduced AF risk (ie, per 2-fold higher
ceramide with
behenic acid hazard ratio, 0.71; 95% CI, 0.59-0.86;
sphingomyelin with
behenic acid hazard ratio, 0.60; 95% CI, 0.46-0.77). In contrast,
ceramides and
sphingomyelins with
palmitic acid were associated with increased AF risk (
ceramide with
palmitic acid hazard ratio, 1.31; 95% CI, 1.03-1.66;
sphingomyelin with
palmitic acid hazard ratio, 1.73; 95% CI, 1.18-2.55). Associations were attenuated with adjustment for
NT-proBNP (N-terminal pro-
B-type natriuretic peptide), but did not differ significantly by age, sex, race, body mass index, or history of
coronary heart disease. Conclusions Our findings suggest that several
ceramide and
sphingomyelin species are associated with incident AF, and that these associations differ on the basis of the
fatty acid.
Ceramides and
sphingomyelins with
palmitic acid were associated with increased AF risk, whereas
ceramides and
sphingomyelins with very-long-chain
saturated fatty acids were associated with reduced AF risk.