背景：BMP10（骨形态发生蛋白10）已成为与房颤（AF）患者缺血性卒中风险和其他预后相关的新型生物标志物。该研究旨在确定重复的BMP10测量是否能改善房颤患者心血管事件的预后。
结果：在ARISTOTLE（阿哌沙班减少房颤中的卒中和其他血栓栓塞事件）试验（n=2878）中随机分配给阿哌沙班或华法林的房颤患者中，使用原型Elecsys免疫测定法在随机分组时和2个月后收集的血浆样本中测量BMP10。使用调整后的Cox回归模型来评估2个月BMP10水平与结果之间的关联。BMP10水平在2个月内增加了7.8％（P<0.001）。2个月时与BMP10水平密切相关的基线变量是基线BMP10水平，身体质量指数,性别,年龄,肌酐,糖尿病,华法林治疗,和AF节奏。在平均1.8年的随访期间，34缺血性中风/全身性栓塞，155人死亡,99例心力衰竭住院。将第三个与第一个样本四分位数进行比较，2个月时较高的BMP10水平与较高的缺血性卒中风险相关(风险比[HR],1.33[95%CI，0.67-2.63]，P=0.037),心力衰竭（HR，1.91[95%CI，1.17-3.12]，P=0.012)和全因死亡(HR，1.61[95%CI，1.17-2.21]，P<0.001)。在已确定的危险因素和基线BMP10水平的基础上，在2个月时添加BMP10水平可改善缺血性卒中/全身性栓塞的C指数（从0.73至0.75），心力衰竭住院（0.76-0.77），全因死亡率（0.70-0.72），均P<0.05。
结论：2个月时BMP10水平升高加强了与缺血性卒中风险的关联，心力衰竭住院治疗,和全因死亡率。重复测量BMP10可以进一步改善房颤患者的风险分层。
BACKGROUND: BMP10 (bone morphogenic protein 10) has emerged as a novel biomarker associated with the risk of ischemic stroke and other outcomes in patients with atrial fibrillation (AF). The
study aimed to determine if repeated
BMP10 measurements improve prognostication of cardiovascular events in patients with AF.
RESULTS: BMP10 was measured using a prototype Elecsys immunoassay in plasma samples collected at randomization and after 2 months in patients with AF randomized to apixaban or warfarin in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation)
trial (n=2878). Adjusted Cox-regression models were used to evaluate the association between 2-month BMP10 levels and outcomes.
BMP10 levels increased by 7.8% (P<0.001) over 2 months. The baseline variables most strongly associated with
BMP10 levels at 2 months were baseline
BMP10 levels, body mass index, sex, age, creatinine, diabetes, warfarin treatment, and AF-rhythm. During median 1.8 years follow-up, 34 ischemic strokes/systemic embolism, 155 deaths, and 99 heart failure hospitalizations occurred. Comparing the third with the first sample quartile, higher BMP10 levels at 2 months were associated with higher risk of ischemic stroke (hazard ratio [HR], 1.33 [95% CI, 0.67-2.63], P=0.037), heart failure (HR, 1.91 [95% CI, 1.17-3.12], P=0.012) and all-cause death (HR, 1.61 [95% CI, 1.17-2.21], P<0.001). Adding
BMP10 levels at 2 months on top of established risk factors and baseline
BMP10 levels improved the C-indices for ischemic stroke/systemic embolism (from 0.73 to 0.75), heart failure hospitalization (0.76-0.77), and all-cause mortality (0.70-0.72), all P<0.05.
CONCLUSIONS: Elevated levels of BMP10 at 2 months strengthened the associations with the risk of ischemic stroke, hospitalization for heart failure, and all-cause mortality. Repeated measurements of BMP10 may further refine risk stratification in patients with AF.
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