Abstract P492: Circulating Sphingolipids and Risk of Mortality: The Cardiovascular Health Study

Abstract

Introduction: Recent studies suggest that the type of saturated fatty acid bound to sphingolipids influences sphingolipid activity, and that associations of ceramides (Cer) and sphingomyelins (SM) with cardiovascular outcomes may differ by lipid species. The purpose of this study was to assess associations of Cer and SM species with mortality among 4,612 older adults from the Cardiovascular Health Study, a population-based prospective study of adults aged ≥65 y who were followed from 1992-2015. Hypothesis: Higher levels of circulating Cer and SM with palmitic acid (Cer-16) are associated with a higher risk of mortality (i.e., deaths from cardiovascular disease (CVD) and non-cardiovascular causes) while higher levels of Cer and SM with very-long chain saturated fatty acids arachidic acid (Cer-20 and SM-20), behenic acid (Cer-22 and SM-22), and lignoceric acid (Cer-24 and SM-24) are associated with a lower risk. Methods: The associations of each sphingolipid with mortality were assessed using Cox proportional hazards models. Models adjusted for age, sex, self-reported race, geographic area, education, smoking, alcohol use, BMI, activities of daily living, HDL and LDL cholesterol, triglycerides, systolic blood pressure, physical activity, use of hypertension or lipid-lowering drugs, self-reported health status, prevalent diabetes, CVD, heart failure (HF), and other sphingolipids species. Results: During a median follow-up of 10.2 years (range 0-23 years), 4,099 deaths occurred. At each time, higher levels of Cer-16 and SM-16 were associated with a higher risk of mortality, while higher levels of Cer-22, Cer-24, SM-20, SM-22, and SM-24 were associated with a lower risk of mortality (Figure). Models that did not adjust for diabetes, CVD, and HF produced similar results. Conclusions: These findings suggest that the associations of Cer and SM with the risk of death differ according to the length of their acylated saturated fatty acid, and support the need for future studies to explore mechanisms underlying these relations.