Endotrophin, a Collagen VI Formation-Derived Peptide, in Heart Failure.
Endotrophin, a Collagen VI Formation-Derived Peptide, in Heart Failure.
复制标题
DOI：
10.1056/evidoa2200091
复制
发表时间：
2022-10
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
内养蛋白是一种 VI 型胶原蛋白衍生肽，可在动物模型中介导代谢失调、炎症和纤维化，但尚未在人类心力衰竭 (HF) 中进行研究。我们研究了参加 TOPCAT 试验 (n=205) 的射血分数保留 (HFpEF) 心力衰竭参与者的循环内皮素与结果之间的关联。关联性在一项参与者级荟萃分析 (n=810) 中得到验证，该分析包括来自 PHFS 研究的 HFpEF 参与者（美国；n=174）、PEOPLE 队列（新西兰；n=168）、一项血管扩张剂治疗随机试验（美国；n=45）、来自 Donostia 大学医院和纳瓦拉大学的队列（西班牙；n=171）以及 TRAINING-HF 试验（西班牙；n=171）。 n=47）。我们还评估了 HF 与 PHFS 射血分数降低的关联 (n=1,642)。 TOPCAT 中，基线血浆内养蛋白水平与未来死亡风险（标准化风险比 [HR] = 1.74；95% 置信区间 [CI]=1.36–2.24；P<0.001）以及死亡或心力衰竭相关入院风险（DHFA；标准化 HR=2.11；95% CI= 1.67–2.67；P<0.001）相关。除了 MAGGIC 风险评分和 NT-proBNP（N 末端 B 型利尿钠肽原）之外，内养蛋白还改善了这些结果的重新分类和区分。研究结果在参与者层面的荟萃分析中得到了证实。在射血分数降低的 PHFS 心衰参与者中，内养蛋白水平与死亡相关（标准化 HR=1.82；95% CI=1.66–2.00；P<0.001）和 DHFA（标准化 HR=1.40；95% CI=1.31–1.50；P<0.001），但后者关联的强度明显低于 MAGGIC 风险评分（标准化HR=1.93；95% CI=1.76–2.12）和 BNP（标准化 HR=1.78；95% CI=1.66–1.92）。循环内皮素水平与 HF 患者（尤其是 HFpEF）未来的不良预后独立相关。 （由百时美施贵宝、Instituto de Salud Carlos III [西班牙] 和欧洲区域发展基金、欧盟委员会关键项目以及美国国立卫生研究院国家心肺血液研究所资助。）
Endotrophin, a collagen type VI-derived peptide, mediates metabolic dysregulation, inflammation, and fibrosis in animal models, but has not been studied in human heart failure (HF). We examined the association between circulating endotrophin and outcomes in participants suffering from HF with preserved ejection fraction (HFpEF) enrolled in the TOPCAT trial (n=205). Associations were validated in a participant-level meta-analysis (n=810) that included participants with HFpEF from the PHFS study (United States; n=174), PEOPLE cohort (New Zealand; n=168), a randomized trial of vasodilator therapy (United States; n=45), a cohort from Donostia University Hospital and University of Navarra (Spain; n=171), and the TRAINING-HF trial (Spain; n=47). We also assessed associations in HF with reduced ejection fraction in PHFS (n=1,642). Plasma endotrophin levels at baseline were associated with risk of future death (standardized hazard ratio [HR] = 1.74; 95% confidence interval [CI]=1.36–2.24; P<0.001) and death or HF-related hospital admission (DHFA; standardized HR=2.11; 95% CI= 1.67–2.67; P<0.001) in TOPCAT. Endotrophin improved reclassification and discrimination for these outcomes beyond the MAGGIC risk score and NT-proBNP (N-terminal pro b-type natriuretic peptide). Findings were confirmed in the participant-level meta-analysis. In participants with HF with reduced ejection fraction in PHFS, endotrophin levels were associated with death (standardized HR=1.82; 95% CI=1.66–2.00; P<0.001) and DHFA (standardized HR=1.40; 95% CI=1.31–1.50; P<0.001), but the strength of the latter association was substantially lower than for the MAGGIC risk score (standardized HR=1.93; 95% CI=1.76–2.12) and BNP (standardized HR=1.78; 95% CI=1.66–1.92). Circulating endotrophin levels are independently associated with future poor outcomes in patients with HF, particularly in HFpEF. (Funded by Bristol Myers Squibb; Instituto de Salud Carlos III [Spain] and European Regional Development Fund; European Commission CRUCIAL project; and the U.S. National Institutes of Health National Heart, Lung, and Blood Institute.)