Ma Ronald C W, Tam Claudia H T, Hou Yong, Lau Eric S H, Ozaki Risa, Lui Juliana N M, Chow Elaine, Kong Alice P S, Huang Chuiguo, Ng Alex C W, Fung Erik G, Luk Andrea O Y, So Wing Yee, Lim Cadmon K P, Chan Juliana C N
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, HKSAR, China.
Laboratory for Molecular Epidemiology in Diabetes, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, HKSAR, China.
Diabetologia. 2025 Feb;68(2):342-356. doi: 10.1007/s00125-024-06299-x. Epub 2024 Nov 7.
AIMS/HYPOTHESIS: N-terminal pro B-type natriuretic peptide (NT-proBNP) is a natriuretic peptide that is strongly associated with congestive heart failure (CHF). The utility of NT-proBNP for prediction of cardiovascular events and renal endpoints, compared with clinical risk factors, has not been evaluated in detail. We hypothesise that NT-proBNP can improve risk stratification and prediction of cardiorenal events in type 2 diabetes, beyond that provided by clinical risk factors.
NT-proBNP was measured in 1993 samples from the Hong Kong Diabetes Biobank, a multicentre prospective diabetes cohort and biobank. A cut-off of ≥125 pg/ml was used to define elevated NT-proBNP. Associations between elevated NT-proBNP and incident cardiovascular and renal endpoints were examined using Cox regression, adjusted for sex, age and duration of diabetes, as well as other covariates. Prognostic and incremental predictive values of NT-proBNP in diabetes cardiorenal complications, compared with those of the Joint Asia Diabetes Evaluation risk equations for CHD, CHF and kidney failure, were evaluated using the concordance index (C index), net reclassification improvement index, integrated discrimination improvement index and relative integrated discrimination improvement index.
A total of 24.7% of participants had elevated NT-proBNP. Participants with elevated NT-proBNP at baseline had a more adverse cardiometabolic profile, with 2-4-fold higher frequency of complications at baseline. Adjusting for age at baseline, sex and duration of diabetes, elevated NT-proBNP was associated with incident atrial fibrillation (HR 4.64 [95% CI 2.44, 8.85]), CHD (HR 4.21 [2.46, 7.21]), CVD (HR 3.32 [2.20, 5.01]) and CHF (HR 4.18 [2.18, 8.03]; all p<0.001). All these associations remained significant after further adjustment for additional covariates. Elevated NT-proBNP had good discriminative ability for various cardiorenal endpoints, with C index of 0.83 (95% CI 0.76, 0.90) for CHD, 0.88 (0.81, 0.94) for atrial fibrillation, 0.89 (0.83, 0.95) for CHF, 0.81 (0.77, 0.84) for 40% drop in eGFR and 0.88 (0.84, 0.92) for kidney failure. Models incorporating NT-proBNP had improved prediction compared with established clinical risk models. Sensitivity analyses including alternative cut-off of NT-proBNP, as well as use of other risk engines of CHD, yielded similar results.
CONCLUSIONS/INTERPRETATION: NT-proBNP demonstrated a promising ability to serve as a prognostic marker for a variety of cardiorenal complications in type 2 diabetes. Considering NT-proBNP in clinical assessments could potentially help identify high-risk individuals who may benefit from more intensive therapies.
目的/假设:N 末端 B 型利钠肽原(NT-proBNP)是一种与充血性心力衰竭(CHF)密切相关的利钠肽。与临床风险因素相比,NT-proBNP 在预测心血管事件和肾脏终点方面的效用尚未得到详细评估。我们假设,NT-proBNP 能够改善 2 型糖尿病患者的心肾事件风险分层和预测,其作用超过临床风险因素。
在香港糖尿病生物样本库(一个多中心前瞻性糖尿病队列和生物样本库)的 1993 份样本中测量 NT-proBNP。NT-proBNP 升高的定义为≥125 pg/ml。使用 Cox 回归分析 NT-proBNP 升高与心血管和肾脏终点事件之间的关联,并对性别、年龄、糖尿病病程以及其他协变量进行校正。与冠心病、CHF 和肾衰竭的亚洲糖尿病联合评估风险方程相比,使用一致性指数(C 指数)、净重新分类改善指数、综合判别改善指数和相对综合判别改善指数评估 NT-proBNP 在糖尿病心肾并发症中的预后和增量预测价值。
共有 24.7%的参与者 NT-proBNP 升高。基线时 NT-proBNP 升高的参与者具有更不利的心脏代谢特征指标,基线时并发症发生频率高出 2 至 4 倍。在校正基线年龄、性别和糖尿病病程后,NT-proBNP 升高与心房颤动(HR 4.64 [95% CI 2.44, 8.85])、冠心病(HR 4.21 [2.46, 7.21])、心血管疾病(CVD,HR 3.32 [2.20, 5.01])和 CHF(HR 4.18 [2.18, 8.03];所有 p<0.001)相关。在进一步校正其他协变量后,所有这些关联仍然显著。NT-proBNP 升高对各种心肾终点具有良好的判别能力,冠心病的 C 指数为 0.83(95% CI 0.76, 0.90),心房颤动为 0.88(0.81, 0.94),CHF 为 0.89(0.83, 0.95),估算肾小球滤过率(eGFR)下降 40%为 0.81(0.77, 0.84),肾衰竭为 0.88(0.84, 0.92)。与既定的临床风险模型相比,纳入 NT-proBNP 的模型预测能力有所提高。敏感性分析包括 NT-proBNP 的替代临界值以及使用其他冠心病风险评估工具,结果相似。
结论/解读:NT-proBNP 显示出有望作为 2 型糖尿病各种心肾并发症预后标志物的能力。在临床评估中考虑 NT-proBNP 可能有助于识别可能从强化治疗中获益的高危个体。