Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
JACC Heart Fail. 2018 Mar;6(3):246-256. doi: 10.1016/j.jchf.2017.12.014. Epub 2018 Feb 7.
The purpose of this study was to assess the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiovascular (CV) versus non-CV events and between NT-proBNP and potential treatment effects in heart failure (HF) with preserved, mid-range, and reduced ejection fraction (HFpEF, HFmrEF, and HFrEF, respectively) and clinically relevant subgroups.
Optimizing patient eligibility criteria in HF trials requires biomarkers that enrich for CV but not for non-CV events and select patients most likely to respond to the tested intervention.
In the Swedish HF registry population stratified by EF category, we used Kaplan-Meier curves to estimate unadjusted CV and non-CV risks (mortality or hospitalization); Poisson regressions to calculate crude event rates of CV and non-CV events according to NT-proBNP levels; and Cox regressions to calculate the adjusted hazard ratios for HF therapies according to NT-proBNP ≤ or > median.
In a cohort of 15,849 patients (23% HFpEF, 21% HFmrEF, 56% HFrEF), median NT-proBNP was 2,037, 2,192, and 3,141 pg/ml, respectively. With increasing NT-proBNP, CV event rates increased more steeply than non-CV rates (range 20 to 160 and 30 to 100 per 100 patient-years in HFpEF; 20 to 130 and 20 to 100 in HFmrEF; and 20 to 110 and 20 to 50 in HFrEF, respectively). The CV-to-non-CV ratio increased with increasing NT-proBNP in HFpEF and HFrEF, but only in the lower range in HFmrEF. The association between treatments (e.g., angiotensin-converting enzyme-inhibitor, angiotensin II receptor blockers, and beta-blockers) and outcomes was consistent in NT-proBNP ≤ and > median.
In HF trial design in different EF categories, NT-proBNP may be a useful tool for eligibility and enrichment for CV events, but its role in predicting a potential treatment response remains unclear.
本研究旨在评估 N 末端脑利钠肽前体（NT-proBNP）与心血管（CV）与非 CV 事件之间的相关性，以及在射血分数保留、中间范围和降低的心衰（HFpEF、HFmrEF 和 HFrEF）中，NT-proBNP 与潜在治疗效果之间的相关性，并分析临床相关亚组。
优化心衰试验的患者入选标准需要生物标志物，这些标志物可以增加 CV 事件的发生率，而不会增加非 CV 事件的发生率，并选择最有可能对所测试干预措施有反应的患者。
在按 EF 分类的瑞典心衰登记人群中，我们使用 Kaplan-Meier 曲线估计未经调整的 CV 和非 CV 风险（死亡率或住院率）；泊松回归计算根据 NT-proBNP 水平计算 CV 和非 CV 事件的粗发生率；Cox 回归计算根据 NT-proBNP < 或 > 中位数，计算 HF 治疗的调整后危险比。
在 15849 名患者的队列中（23% HFpEF、21% HFmrEF、56% HFrEF），中位 NT-proBNP 分别为 2037、2192 和 3141pg/ml。随着 NT-proBNP 的增加，CV 事件发生率的增加比非 CV 事件更陡峭（HFpEF 中分别为每 100 患者年 20 至 160 例和 30 至 100 例；HFmrEF 中分别为 20 至 130 例和 20 至 100 例；HFrEF 中分别为 20 至 110 例和 20 至 50 例）。随着 NT-proBNP 的增加，HFpEF 和 HFrEF 中的 CV 与非 CV 比值增加，但在 HFmrEF 中仅在较低范围内增加。在 NT-proBNP < 或 > 中位数时，治疗（如血管紧张素转换酶抑制剂、血管紧张素 II 受体阻滞剂和β受体阻滞剂）与结局之间的相关性是一致的。
在不同 EF 类别的心衰试验设计中，NT-proBNP 可能是一种有用的工具，用于 CV 事件的入选和富集，但它在预测潜在治疗反应方面的作用尚不清楚。
