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.
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。