Cardiovascular Health Research Unit, Department of Medicine (R.N.L., P.N.J., B.M.P., S.R.H., N.S.), University of Washington, Seattle.
Department of Laboratory Medicine (A.H.), University of Washington, Seattle.
Circ Heart Fail. 2019 Jul;12(7):e005708. doi: 10.1161/CIRCHEARTFAILURE.118.005708. Epub 2019 Jul 12.
Ceramides exhibit multiple biological activities that may influence the pathophysiology of heart failure. These activities may be influenced by the saturated fatty acid carried by the ceramide (Cer). However, the associations of different circulating Cer species, and their sphingomyelin (SM) precursors, with heart failure have received limited attention.
We studied the associations of plasma Cer and SM species with incident heart failure in the Cardiovascular Health Study. We examined 8 species: Cer and SM with palmitic acid (Cer-16 and SM-16), species with arachidic acid (Cer-20 and SM-20), species with behenic acid (Cer-22 and SM-22), and species with lignoceric acid (Cer-24 and SM-24). During a median follow-up of 9.4 years, we identified 1179 cases of incident heart failure among 4249 study participants. In Cox regression analyses adjusted for risk factors, higher levels of Cer-16 and SM-16 were associated with higher risk of incident heart failure (hazard ratio for one SD increase:1.25 [95% CI, 1.16-1.36] and 1.28 [1.18-1.40], respectively). In contrast, higher levels of Cer-22 were associated with lower risk of heart failure in multivariable analyses further adjusted for Cer-16 (hazard ratio, 0.85 [0.78-0.92]); and higher levels of SM-20, SM-22 and SM-24 were associated with lower risk of heart failure in analyses further adjusted for SM-16 (hazard ratios, 0.83 [0.77-0.90], 0.81 [0.75-0.88], and 0.83 [0.77-0.90], respectively). No statistically significant interactions with age, sex, black race, body mass index, or baseline coronary heart disease were detected. Similar associations were observed for heart failure with preserved (n=529) or reduced (n=348) ejection fraction.
This study shows associations of higher plasma levels of Cer-16 and SM-16 with increased risk of heart failure and higher levels of Cer-22, SM-20, SM-22, and SM-24 with decreased risk of heart failure.
URL: https://www.clinicaltrials.gov . Unique identifier: NCT00005133.
神经酰胺表现出多种可能影响心力衰竭病理生理学的生物学活性。这些活性可能受到神经酰胺（Cer）所携带的饱和脂肪酸的影响。然而，不同循环 Cer 种类及其神经鞘磷脂（SM）前体与心力衰竭之间的关联尚未得到广泛关注。
我们在心血管健康研究中研究了血浆 Cer 和 SM 种类与心力衰竭事件的相关性。我们检查了 8 种 Cer 和 SM 种类：带有棕榈酸的 Cer（Cer-16 和 SM-16）、带有花生四烯酸的 Cer（Cer-20 和 SM-20）、带有山萮酸的 Cer（Cer-22 和 SM-22）和带有二十四烷酸的 Cer（Cer-24 和 SM-24）。在中位随访 9.4 年期间，我们在 4249 名研究参与者中发现了 1179 例心力衰竭事件。在调整风险因素的 Cox 回归分析中，Cer-16 和 SM-16 水平升高与心力衰竭事件风险增加相关（SD 增加的风险比：1.25 [95%CI，1.16-1.36] 和 1.28 [1.18-1.40]）。相比之下，进一步调整 Cer-16 后，较高的 Cer-22 水平与心力衰竭风险降低相关（风险比，0.85 [0.78-0.92]）；进一步调整 SM-16 后，较高的 SM-20、SM-22 和 SM-24 水平与心力衰竭风险降低相关（风险比，0.83 [0.77-0.90]、0.81 [0.75-0.88]和 0.83 [0.77-0.90]）。未检测到与年龄、性别、黑种人、体重指数或基线冠心病的统计学显著交互作用。在保留（n=529）或降低（n=348）射血分数的心力衰竭中也观察到类似的相关性。
本研究表明，较高的血浆 Cer-16 和 SM-16 水平与心力衰竭风险增加相关，而较高的 Cer-22、SM-20、SM-22 和 SM-24 水平与心力衰竭风险降低相关。
