Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, U.K.
George Institute for Global Health, University of Sydney, Sydney, Australia.
Diabetes Care. 2014 Aug;37(8):2202-10. doi: 10.2337/dc13-2625. Epub 2014 May 30.
We investigated microvascular event risk in people with type 2 diabetes and assessed whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) improved prediction.
We performed a case-cohort study, including 439 incident cases of microvascular events (new or worsening nephropathy or retinopathy) and 2,946 noncase subjects identified from participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. NT-proBNP and hsTnT were measured in stored plasma samples using automated commercial assays.
After adjustment for age, sex, and randomized treatment, the hazard ratios for microvascular events per 1-SD increase in the log-transformed hsTnT and NT-proBNP were 1.67 (95% CI 1.51-1.85) and 1.63 (1.44-1.84), respectively. After further adjustment for classical and diabetes-related cardiovascular disease risk factors, the hazard ratios attenuated to 1.40 (1.24-1.58) and 1.41 (1.24-1.60), respectively. While the C statistic did not improve on addition of hsTnT or NT-proBNP for the total microvascular end point, a combination of both markers improved the prediction of nephropathy (P = 0.033) but not retinopathy (P = 0.72). The corresponding net reclassification indices in a three-risk category model (<10%, 10-15%, and >15% 5-year risk) for all microvascular events were 7.31% (95% CI 2.24-12.79) for hsTNT addition, 6.23% (1.74-11.5) for NT-proBNP addition, and 7.1% (1.5-12.9) for both markers together.
These data suggest that cardiac biomarkers moderately improve microvascular event risk prediction, in particular the risk of nephropathy. Further studies examining the value of this approach for trial design and clinical use are warranted.
我们研究了 2 型糖尿病患者微血管事件的风险，并评估了 N 末端脑钠肽前体（NT-proBNP）和高敏肌钙蛋白 T（hsTnT）是否能改善预测。
我们进行了一项病例-队列研究，包括 439 例微血管事件（新发生或恶化的肾病或视网膜病变）的病例和从 ADVANCE 试验中确定的 2946 名非病例受试者。使用自动化商业检测法测量储存在血浆样本中的 NT-proBNP 和 hsTnT。
在调整年龄、性别和随机治疗后，log 转换后 hsTnT 和 NT-proBNP 每增加 1-SD，微血管事件的风险比分别为 1.67（95%CI 1.51-1.85）和 1.63（1.44-1.84）。进一步调整经典和与糖尿病相关的心血管疾病危险因素后，风险比分别减弱至 1.40（1.24-1.58）和 1.41（1.24-1.60）。虽然添加 hsTnT 或 NT-proBNP 并未提高总微血管终点的 C 统计量，但两者标志物的组合改善了肾病（P=0.033）但未改善视网膜病变（P=0.72）的预测。在三风险类别模型（<10%、10-15%和>15%的 5 年风险）中，所有微血管事件的净重新分类指数（net reclassification index，NRI）分别为 hsTNT 增加 7.31%（95%CI 2.24-12.79）、NT-proBNP 增加 6.23%（1.74-11.5）和两个标志物一起增加 7.1%（1.5-12.9）。
这些数据表明，心脏生物标志物可适度改善微血管事件风险预测，尤其是肾病的风险。需要进一步研究来检验这种方法在临床试验设计和临床应用中的价值。
