Background Recent studies suggest that associations of ceramides (Cer) and sphingomyelins (SM) with health outcomes differ according to the fatty acid acylated to the sphingoid backbone. The purpose of this study was to assess associations of Cer and SM species with mortality. Methods The study population included participants from the Cardiovascular Health Study (CHS), a community-based cohort of adults aged ≥65 years who were followed from 1992–2015 (n = 4612). Associations of plasma Cer and SM species carrying long-chain (i.e., 16:0) and very-long-chain (i.e., 20:0, 22:0, 24:0) saturated fatty acids with mortality were assessed using Cox proportional hazards models. Results During a median follow-up of 10.2 years, 4099 deaths occurred. High concentrations of Cer and SM carrying fatty acid 16:0 were each associated with an increased risk of mortality. Conversely, high concentrations of several ceramide and sphingomyelin species carrying longer fatty acids were each associated with a decreased risk of mortality. The hazard ratios for total mortality per 2-fold difference in each Cer and SM species were: 1.89 (95% CI), 1.65–2.17 for Cer-16, 0.79 (95% CI, 0.70–0.88) for Cer-22, 0.74 (95% CI, 0.65–0.84) for Cer-24, 2.51 (95% CI, 2.01–3.14) for SM-16, 0.68 (95% CI, 0.58–0.79) for SM-20, 0.57 (95% CI, 0.49–0.67) for SM-22, and 0.66 (0.57–0.75) for SM-24. We found no association of Cer-20 with risk of death. Conclusions Associations of Cer and SM with the risk of death differ according to the length of their acylated saturated fatty acid. Future studies are needed to explore mechanisms underlying these relationships.

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循环神经酰胺和鞘磷脂与死亡风险：心血管健康研究

背景 最近的研究表明，神经酰胺 (Cer) 和鞘磷脂 (SM) 与健康结果的关联因鞘氨醇骨架酰化的脂肪酸而异。本研究的目的是评估 Cer 和 SM 物种与死亡率的关联。方法 研究人群包括心血管健康研究 (CHS) 的参与者，这是一个基于社区的 65 岁以上成年人队列，于 1992 年至 2015 年进行随访 (n = 4612)。使用 Cox 比例风险评估携带长链（即 16:0）和极长链（即 20:0、22:0、24:0）饱和脂肪酸的血浆 Cer 和 SM 物种与死亡率的关联楷模。结果 在中位随访 10.2 年期间，有 4099 人死亡。携带脂肪酸 16:0 的高浓度 Cer 和 SM 均与死亡风险增加相关。相反，高浓度的几种携带较长脂肪酸的神经酰胺和鞘磷脂物种均与死亡风险降低相关。每个 Cer 和 SM 物种每 2 倍差异的总死亡率风险比为：1.89 (95% CI)，Cer-16 为 1.65–2.17，Cer-22 为 0.79 (95% CI，0.70–0.88)，Cer-22 为 0.74 (95% CI, 0.65–0.84) Cer-24, 2.51 (95% CI, 2.01–3.14) SM-16, 0.68 (95% CI, 0.58–0.79) SM-20, 0.57 (95% CI, 2.01–3.14) SM-22 为 0.49–0.67)，SM-24 为 0.66 (0.57–0.75)。我们发现 Cer-20 与死亡风险没有关联。结论 Cer 和 SM 与死亡风险的关联根据其酰化饱和脂肪酸的长度而有所不同。未来的研究需要探索这些关系背后的机制。