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Plasma Ceramides and Sphingomyelins in Relation to Heart Failure Risk.
Circulation: Heart Failure ( IF 9.7 ) Pub Date : 2019-07-12 , DOI: 10.1161/circheartfailure.118.005708
Rozenn N Lemaitre 1 , Paul N Jensen 1 , Andrew Hoofnagle 2 , Barbara McKnight 3 , Amanda M Fretts 4 , Irena B King 5 , David S Siscovick 6 , Bruce M Psaty 1, 4, 7, 8 , Susan R Heckbert 1, 4 , Dariush Mozaffarian 9 , Nona Sotoodehnia 1
Affiliation  

BACKGROUND 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. METHODS AND RESULTS 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. CONCLUSIONS 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. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov . Unique identifier: NCT00005133.

中文翻译:

血浆神经酰胺和鞘磷脂与心力衰竭风险的关系。

背景技术神经酰胺表现出可能影响心力衰竭的病理生理的多种生物学活性。这些活性可能会受到神经酰胺(Cer)携带的饱和脂肪酸的影响。但是,不同的循环Cer物种及其鞘磷脂(SM)前体与心力衰竭的联系受到了有限的关注。方法和结果我们在心血管健康研究中研究了血浆Cer和SM物种与心力衰竭的相关性。我们检查了8种:棕榈酸的Cer和SM(Cer-16和SM-16),花生四烯酸的物种(Cer-20和SM-20),山hen酸的物种(Cer-22和SM-22)以及木质酸的物种(Cer-24和SM-24)。在9.4年的中位随访期间,我们在4249名研究参与者中确定了1179例心力衰竭事件。在针对风险因素进行校正的Cox回归分析中,较高的Cer-16和SM-16水平与较高的事件性心力衰竭风险相关(一种SD的危险比增加:1.25 [95%CI,1.16-1.36]和1.28 [1.18] -1.40])。相比之下,在进一步针对Cer-16进行调整的多变量分析中,较高的Cer-22水平与较低的心力衰竭风险相关(危险比,0.85 [0.78-0.92]);在进一步针对SM-16进行调整的分析中,较高的SM-20,SM-22和SM-24水平与较低的心衰风险相关(危险比,0.83 [0.77-0.90],0.81 [0.75-0.88]和分别为0.83 [0.77-0.90]。未发现与年龄,性别,黑人,体重指数或基线冠心病有统计学意义的相互作用。对于心力衰竭观察到相似的关联,射血分数保留(n = 529)或射血分数降低(n = 348)。结论本研究表明,血浆Cer-16和SM-16的较高水平与心力衰竭风险增加相关,而血浆Cer-22,SM-20,SM-22和SM-24的较高水平与心力衰竭风险降低相关。临床试验注册网址:https://www.clinicaltrials.gov。唯一标识符:NCT00005133。
更新日期:2019-11-01
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