Risk for Incident AF Associated With Plasma Levels of Ceramides, Sphingomyelin

An increased risk for incident atrial fibrillation (AF) was found to be associated with plasma levels of ceramides and sphingomyelins with palmitic acid, while plasma levels of ceramides and sphingomyelins with very-long-chain saturated fatty acids (VLSFAs) were associated with a reduction in incident AF risk, according to study results published in the Journal of the American Heart Association.

This is a sub-analysis of the Cardiovascular Health Study, a community-based prospective cohort study in which cardiovascular disease risk factors were examined in 4206 adults (age ≥65 years; mean age, 76±5 years; 40% men) without AF at baseline. Study participants were followed for up to 10 years and given annual examinations between 1989 and 1999. Sphingolipids were measured from 1992 to 1995 and included plasma levels of 8 species: ceramides and sphingomyelins with palmitic acid, as well as species with VLSFAs (ie, arachidic acid, lignoceric acid, and behenic acid).

During a median follow-up of 8.7 years, 1198 cases of incident AF (28.5%) occurred in this cohort (incidence rate, 33 per 1000 person-years). Ceramide and sphingomyelin species with VLSFAs were found to be associated with a reduction in the risk for incident AF: including those with arachidic acid (ceramide with arachidic acid: hazard ratio [HR], 0.72; 95% CI, 0.61-0.84; P <.0001), sphingomyelin with arachidic acid (HR, 0.55; 95% CI, 0.43-0.71; P <.0001), behenic acid (ceramide with behenic acid: HR, 0.71; 95% CI, 0.59-0.86; P =.0004; sphingomyelin with behenic acid: HR, 0.60; 95% CI, 0.46-0.77; P =.0001) and lignoceric acid (ceramide with lignoceric acid: HR, 0.67; 95% CI, 0.54-0.83; P =.0003; sphingomyelin with lignoceric acid: HR, 0.76; 95% CI, 0.61-0.94; P =.0124).

In contrast, an association between and an increased risk in incident AF and levels of ceramide and sphingomyelin species with palmitic acid was established (ceramide with palmitic acid: HR, 1.31; 95% CI, 1.03-1.66; P =.0274; sphingomyelin with palmitic acid: HR, 1.73; 95% CI, 1.18-2.55; P =.0051).

When the results were adjusted for N-terminal pro-B-type natriuretic peptide levels, there was an attenuation effect on most associations, such that only levels of ceramide with arachidic acid retained a significant association with incident AF (HR, 0.82; 95% CI, 0.69-0.97; P =.0246). Adjustments for age, sex, body mass index, or coronary heart disease history did not affect those relationships.

Study strengths include a detailed assessment of species variables and covariates and a high rate of AF incidence in participants. Study limitations include its observational design that precludes causal inference, inability to differentiate permanent from paroxysmal AF subtypes, the possible lack of identification of some inactive AF cases, a lack of generalizability to younger populations or other ethnicities, and singular laboratory and biomarker measurements.

“If the associations prove to be causal, increasing levels of ceramide and sphingomyelin species with a VLSFA and lowering levels of species with palmitic acid may be useful therapeutic targets for the prevention of AF,” noted the authors. They recommended that future research look to replicate their findings in younger populations and evaluate the potential use of species’ plasma levels as components of AF risk scores.

Reference

Jensen PN, Fretts AM, Hoofnagle AN, et al. Plasma ceramides and sphingomyelins in relation to atrial fibrillation risk: the Cardiovascular Health Study. J Am Heart Assoc. 2020;9(4):1-6. doi:10.1161/jaha.119.012853