Neuen Brendon L, Vaduganathan Muthiah, Claggett Brian L, Beldhuis Iris, Myhre Peder, Desai Akshay S, Skali Hicham, Mc Causland Finnian R, McGrath Martina, Anand Inder, Zile Michael R, Pfeffer Marc A, McMurray John J V, Solomon Scott D
Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA; The George Institute for Global Health, University of New South Wales, Sydney, Australia; Department of Renal Medicine, Royal North Shore Hospital, Sydney, Australia.
Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Division of Cardiovascular Medicine, Center for Cardiometabolic Implementation Science, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
JACC Heart Fail. 2025 Jan;13(1):28-39. doi: 10.1016/j.jchf.2024.08.009. Epub 2024 Aug 31.
N-terminal pro-B-type natriuretic peptides (NT-proBNPs) are guideline-recommended biomarkers for risk stratification in patients with heart failure. However, NT-proBNP levels are often elevated in chronic kidney disease, introducing uncertainty about their prognostic relevance in persons across a broad range of estimated glomerular filtration rate (eGFR).
The aim of this study was to assess the association of NT-proBNP with cardiovascular and mortality outcomes in patients with heart failure and mildly reduced or preserved ejection fraction, stratified by baseline kidney function.
A pooled analysis was conducted of participants with NT-proBNP and eGFR measured at baseline in the I-PRESERVE (Irbesartan in Heart Failure and Preserved Ejection Fraction), TOPCAT (Americas region) (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function), PARAGON (Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction), and DELIVER (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure) trials. The relationship between NT-proBNP and eGFR was assessed using piecewise linear regression. Using multivariable Cox and Poisson regression models, the association of NT-proBNP with outcomes across a range of eGFR was evaluated. The primary outcome was hospitalization for heart failure or cardiovascular death.
Among 14,831 participants (mean age: 72.1 years; 50.3% female; mean eGFR: 63.3 mL/min/1.73 m, and median NT-proBNP: 840 pg/mL) followed up for a median 33.5 months, there were 3,092 primary outcomes. NT-proBNP levels increased by 9%, 8%, and 23% per 10 mL/min/1.73 m lower eGFR in patients with baseline eGFR ≥60, 45-<60, and <45 mL/min/1.73 m, respectively (P for nonlinearity < 0.001). Each doubling in NT-proBNP was associated with a 37% relative increase in the primary outcome (HR: 1.37; 95% CI: 1.34-1.41), consistent across different eGFR categories (P for interaction = 0.42). For the same incidence of the primary outcome, NT-proBNP levels were approximately 2.5- to 3.5-fold lower in patients with eGFR <45 mL/min/1.73 m, compared with patients with eGFR ≥60 mL/min/1.73 m. Similar patterns were observed across all outcomes studied, including cardiovascular and noncardiovascular death.
The same NT-proBNP concentration predicts a substantially higher absolute risk of adverse outcomes for people with heart failure and reduced kidney function, compared with those with preserved kidney function. These data call into question proposals for higher NT-proBNP references ranges in people with CKD, and suggest that reduced kidney function per se should not be a reason to disregard higher NT-proBNP levels.
N 末端 B 型利钠肽原（NT-proBNP）是心力衰竭患者风险分层的指南推荐生物标志物。然而，慢性肾脏病患者的 NT-proBNP 水平通常会升高，这使得其在广泛的估计肾小球滤过率（eGFR）人群中的预后相关性存在不确定性。
本研究旨在评估 NT-proBNP 与心力衰竭且射血分数轻度降低或保留的患者心血管及死亡结局的关联，并按基线肾功能进行分层。
对 I-PRESERVE（厄贝沙坦治疗心力衰竭和保留射血分数）、TOPCAT（美洲地区）（醛固酮拮抗剂治疗成人心力衰竭和保留收缩功能）、PARAGON（ARNI 与 ARB 在保留射血分数心力衰竭中的全球结局前瞻性比较）和 DELIVER（达格列净评估改善保留射血分数心力衰竭患者生活质量）试验中基线时测量了 NT-proBNP 和 eGFR 的参与者进行汇总分析。使用分段线性回归评估 NT-proBNP 与 eGFR 之间的关系。使用多变量 Cox 和泊松回归模型，评估 NT-proBNP 在一系列 eGFR 范围内与结局的关联。主要结局是因心力衰竭住院或心血管死亡。
在 14831 名参与者（平均年龄：72.1 岁；50.3%为女性；平均 eGFR：63.3 mL/min/1.73m²，NT-proBNP 中位数：840 pg/mL）中进行了中位 33.5 个月的随访，共有 3092 例主要结局。基线 eGFR≥60、45 - <60 和 <45 mL/min/1.73m²的患者，每降低 10 mL/min/1.73m²的 eGFR，NT-proBNP 水平分别升高 9%、8%和 23%（非线性 P<0.001）。NT-proBNP 每增加一倍，主要结局相对增加 37%（HR：1.37；95%CI：1.34 - 1.41），在不同 eGFR 类别中一致（交互作用 P = 0.42）。对于相同的主要结局发生率，与 eGFR≥60 mL/min/1.73m²的患者相比，eGFR<45 mL/min/1.73m²的患者 NT-proBNP 水平约低 2.5 至 3.5 倍。在所有研究的结局中均观察到类似模式，包括心血管和非心血管死亡。
与肾功能正常的心力衰竭患者相比，相同的 NT-proBNP 浓度预测肾功能降低的心力衰竭患者不良结局的绝对风险要高得多。这些数据对慢性肾脏病患者更高 NT-proBNP 参考范围的提议提出了质疑，并表明肾功能降低本身不应成为忽视较高 NT-proBNP 水平的理由。
