Uppsala Clinical Research Center, Dag Hammarskjölds väg 14B, Uppsala, Sweden.
Circulation. 2012 Apr 3;125(13):1605-16. doi: 10.1161/CIRCULATIONAHA.111.038729. Epub 2012 Feb 28.
Cardiac biomarkers are strong predictors of adverse outcomes in several patient populations. We evaluated the prevalence of elevated troponin I and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and their association to cardiovascular events in atrial fibrillation (AF) patients in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial.
Biomarkers at randomization were analyzed in 6189 patients. Outcomes were evaluated by Cox proportional hazards models adjusting for established cardiovascular risk factors and the CHADS(2) and CHA(2)DS(2)-VASc risk scores. Patients were stratified based on troponin I concentrations: <0.010 μg/L, n=2663; 0.010 to 0.019 μg/L, n=2006; 0.020 to 0.039 μg/L, n=1023; ≥0.040 μg/L, n=497; and on NT-proBNP concentration quartiles: <387; 387 to 800; 801 to 1402; >1402 ng/L. Rates of stroke were independently related to levels of troponin I with 2.09%/year in the highest and 0.84%/year in the lowest troponin I group (hazard ratio [HR], 1.99 [95% CI, 1.17-3.39]; P=0.0040), and to NT-proBNP with 2.30%/year versus 0.92% in the highest versus lowest NT-proBNP quartile groups, (HR, 2.40 [95% CI, 1.41-4.07]; P=0.0014). Vascular mortality was also independently related to biomarker levels with 6.56%/year in the highest and 1.04%/year the lowest troponin I group (HR, 4.38 [95% CI, 3.05-6.29]; P<0.0001), and 5.00%/year in the highest and 0.61%/year in the lowest NT-proBNP quartile groups (HR, 6.73 [3.95-11.49]; P<0.0001). Biomarkers increased the C-statistic from 0.68 to 0.72, P<0.0001, for a composite of thromboembolic events.
Elevations of troponin I and NT-proBNP are common in patients with AF and independently related to increased risks of stroke and mortality. Cardiac biomarkers seem useful for improving risk prediction in AF beyond currently used clinical variables.
在多个患者群体中，心脏生物标志物是不良结局的强有力预测因子。我们评估了随机化时肌钙蛋白 I 和 N 末端 B 型利钠肽前体（NT-proBNP）升高的发生率及其与心房颤动（AF）患者心血管事件的关系，该研究来自随机评估长期抗凝治疗（RE-LY）试验。
对 6189 例患者的生物标志物进行了分析。采用 Cox 比例风险模型评估结局，该模型对已确立的心血管危险因素、CHADS2 和 CHA2DS2-VASc 风险评分进行了调整。患者根据肌钙蛋白 I 浓度进行分层：<0.010 μg/L，n=2663；0.010 至 0.019 μg/L，n=2006；0.020 至 0.039 μg/L，n=1023；≥0.040 μg/L，n=497；根据 NT-proBNP 浓度四分位数分层：<387；387 至 800；801 至 1402；>1402ng/L。卒中发生率与肌钙蛋白 I 水平独立相关，最高肌钙蛋白 I 组为 2.09%/年，最低肌钙蛋白 I 组为 0.84%/年（风险比 [HR]，1.99 [95%CI，1.17-3.39]；P=0.0040），与 NT-proBNP 也相关，最高 NT-proBNP 四分位组为 2.30%/年，最低组为 0.92%（HR，2.40 [95%CI，1.41-4.07]；P=0.0014）。血管死亡率也与生物标志物水平独立相关，最高肌钙蛋白 I 组为 6.56%/年，最低肌钙蛋白 I 组为 1.04%/年（HR，4.38 [95%CI，3.05-6.29]；P<0.0001），最高 NT-proBNP 四分位组为 5.00%/年，最低组为 0.61%/年（HR，6.73 [3.95-11.49]；P<0.0001）。生物标志物将 C 统计量从 0.68 提高到 0.72，P<0.0001，用于血栓栓塞事件的综合评估。
在 AF 患者中，肌钙蛋白 I 和 NT-proBNP 的升高很常见，与卒中风险和死亡率的增加独立相关。心脏生物标志物似乎可用于改善 AF 患者的风险预测，超越目前使用的临床变量。
