Ostrominski John W, Neuen Brendon L, Claggett Brian L, Anand Inder S, Desai Akshay S, Jhund Pardeep S, Lam Carolyn S P, Pfeffer Marc A, Pitt Bertram, Zannad Faiez, Zile Michael R, Packer Milton, Docherty Kieran F, McMurray John J V, Solomon Scott D, Vaduganathan Muthiah
: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; : Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
: The George Institute for Global Health, University of New South Wales, Sydney, Australia; : Department of Renal Medicine, Royal North Shore Hospital, Sydney, Australia.
J Am Coll Cardiol. 2025 Aug 19. doi: 10.1016/j.jacc.2025.08.028.
Natriuretic peptides are the primary biomarkers recommended in heart failure (HF) guidelines to risk stratify patients in clinical practice and serve as key eligibility criteria in contemporary clinical trials. However, threshold levels typically do not account for measures of adiposity, such as body mass index (BMI).
To evaluate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) with clinical outcomes in individuals with HF and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), stratified according to BMI.
In this participant-level pooled analysis of 4 global, randomized, outcomes trials including adults with HFmrEF/HFpEF, the association between NT-proBNP and clinical outcomes (cardiovascular death or HF hospitalization, cardiovascular death, HF hospitalization, and all-cause death) was evaluated according to BMI as a continuous and categorical variable.
Among 14,750 participants (mean age, 72±9 years; 50% female; mean BMI, 30±6 kg/m; median NT-proBNP, 836 pg/mL), higher baseline BMI was significantly and non-linearly associated with lower NT-proBNP levels. Over a median follow-up of 2.8 years, each doubling of baseline NT-proBNP was associated with a 40% higher covariate-adjusted rate of cardiovascular death or HF hospitalization (hazard ratio, 1.40; 95% CI, 1.36-1.43; P<0.001). However, this association appeared incrementally blunted with higher baseline BMI (P=0.008). For the same absolute risk of cardiovascular death or HF hospitalization (5 events per 100 person-years), NT-proBNP levels in participants without atrial fibrillation were nearly 3-fold lower among those with BMI ≥35 kg/m (158 pg/mL) vs. <35 kg/m (450 pg/mL). At a contemporary NT-proBNP-based trial eligibility threshold, absolute risk of cardiovascular death or HF hospitalization ranged from 3.5 per 100 person-years among persons with BMI <30 kg/m to 7.3 per 100 person-years among those with BMI ≥40 kg/m.
In this analysis, current NT-proBNP thresholds substantially underestimated the absolute risk of adverse HF outcomes among persons with higher BMI. These data question single fixed thresholds and instead suggest that lower NT-proBNP cutoffs may more appropriately risk stratify patients at higher BMI.
利钠肽是心力衰竭（HF）指南中推荐的主要生物标志物，用于在临床实践中对患者进行风险分层，并作为当代临床试验的关键入选标准。然而，阈值水平通常未考虑肥胖指标，如体重指数（BMI）。
根据BMI进行分层，评估N端前B型利钠肽原（NT-proBNP）与射血分数轻度降低或保留的心力衰竭患者（HFmrEF/HFpEF）临床结局之间的关联。
在这项对4项全球随机结局试验的参与者水平汇总分析中，纳入了HFmrEF/HFpEF成人患者，根据BMI作为连续和分类变量，评估NT-proBNP与临床结局（心血管死亡或HF住院、心血管死亡、HF住院和全因死亡）之间的关联。
在14750名参与者中（平均年龄72±9岁；50%为女性；平均BMI 30±6 kg/m²；NT-proBNP中位数836 pg/mL），较高的基线BMI与较低的NT-proBNP水平显著且呈非线性相关。在中位随访2.8年期间，基线NT-proBNP每增加一倍，经协变量调整的心血管死亡或HF住院发生率就高出40%（风险比1.40；95%CI 1.36-1.43；P<0.001）。然而，随着基线BMI升高，这种关联逐渐减弱（P=0.008）。对于相同的心血管死亡或HF住院绝对风险（每100人年5次事件），在无房颤的参与者中，BMI≥35 kg/m²者的NT-proBNP水平（158 pg/mL）比BMI<35 kg/m²者（450 pg/mL）低近3倍。在基于当代NT-proBNP的试验入选阈值下，心血管死亡或HF住院的绝对风险范围为：BMI<30 kg/m²者每100人年3.5次，BMI≥40 kg/m²者每100人年7.3次。
在本分析中，当前的NT-proBNP阈值大幅低估了BMI较高者发生不良HF结局的绝对风险。这些数据对单一固定阈值提出质疑，相反表明较低的NT-proBNP临界值可能更适当地对BMI较高的患者进行风险分层。
