Kristensen Søren Lund, Jhund Pardeep S, Mogensen Ulrik M, Rørth Rasmus, Abraham William T, Desai Akshay, Dickstein Kenneth, Rouleau Jean L, Zile Michael R, Swedberg Karl, Packer Milton, Solomon Scott D, Køber Lars, McMurray John J V
From the BHF Cardiovascular Research Centre, University of Glasgow, United Kingdom (S.L.K., P.S.J., U.M.M., R.R., J.J.V.M.); Department of Cardiology, Rigshospitalet University Hospital, Copenhagen, Denmark (S.L.K., U.M.M., R.R., L.K.); The Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute, Ohio State University, Columbus (W.TA.); Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.D., S.D.S.); Stavanger University Hospital, Stavanger, and Department of Clinical Science, the Institute of Internal Medicine, University of Bergen, Norway (K.D.); Institut de Cardiologie de Montréal, Université de Montréal, Canada (J.L.R.); Medical University of South Carolina and RHJ Department of Veterans Administration Medical Center, Charleston (M.R.Z.); Department of Molecular and Clinical Medicine, University of Gothenburg, Sweden (K.S.); Faculty of Medicine, National Heart and Lung Institute, Imperial College, London, United Kingdom (K.S.); and Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX (M.P.).
Circ Heart Fail. 2017 Oct;10(10). doi: 10.1161/CIRCHEARTFAILURE.117.004409.
Patients with heart failure (HF) and atrial fibrillation (AF) have higher circulating levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) than HF patients without AF. There is uncertainty about the prognostic importance of a given concentration of NT-proBNP in HF patients with and without AF. We investigated this question in a large cohort of patients with HF and reduced ejection fraction.
We studied 14 737 patients with HF and reduced ejection fraction and a measurement of NT-proBNP at time of screening, enrolled in either the PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) or the ATMOSPHERE trial (Aliskiren Trial to Minimize Outcomes in Patients With Heart Failure), of whom 3575 (24%) had AF on their baseline ECG. Median (Q1, Q3) levels of NT-proBNP were 1817 pg/mL (1095-3266 pg/mL) in those with AF and 1271 pg/mL (703-2569 pg/mL) in those without (<0.0001). Patients with AF were older (67 versus 62 years), had worse New York Heart Association class (III/IV; 36% versus 24%), and experienced fewer previous HF hospitalizations (52% versus 61%) or myocardial infarction (30% versus 46%); all <0.001. We categorized patients with and without AF into 5 NT-proBNP bands: <400, 400 to 999 (reference), 1000 to 1999, 2000 to 2999, and ≥3000 pg/mL. For the primary composite outcome of cardiovascular death or HF hospitalization, event rates differed for patients with and without AF in the lowest band (<400 pg/mL; 8.2 versus 5.0 per 100 patient-years), but not for the higher bands (400-999 pg/mL, 7.4 versus 7.7 per 100 patient-years; 1000-1999 pg/mL, 9.8 versus 11.4 per 100 patient-year; 2000-2999 pg/mL, 13.5 versus 13.4 per 100 patient-years; ≥3000 pg/mL, 22.7 versus 23.0 per 100 patient-years). These findings were consistent whether NT-proBNP was examined as a categorical or continuous variable and before and after adjustment for other prognostic variables. We found similar results for the components of the composite outcome and all-cause mortality.
HF and reduced ejection fraction patients with AF had higher NT-proBNP than those without AF. However, above a concentration of 400 pg/mL (representing most patients in each group), NT-proBNP had similar predictive value for adverse cardiovascular outcomes, irrespective of AF status.
URL: https://www.clinicaltrials.gov. Unique identifier NCT00853658 (ATMOSPHERE) and NCT01035255 (PARADIGM-HF).
心力衰竭（HF）合并心房颤动（AF）患者的N末端B型利钠肽原（NT-proBNP）循环水平高于无AF的HF患者。对于给定浓度的NT-proBNP在有和无AF的HF患者中的预后重要性尚不确定。我们在一大群射血分数降低的HF患者中研究了这个问题。
我们研究了14737例射血分数降低的HF患者，并在筛查时测量了NT-proBNP，这些患者入选了PARADIGM-HF试验（ARNI与ACEI前瞻性比较以确定对心力衰竭全球死亡率和发病率的影响）或ATMOSPHERE试验（阿利吉仑试验以最小化心力衰竭患者的结局），其中3575例（24%）在基线心电图时有AF。有AF患者的NT-proBNP中位数（Q1，Q3）水平为1817 pg/mL（1095 - 3266 pg/mL），无AF患者为1271 pg/mL（703 - 2569 pg/mL）（<0.0001）。有AF的患者年龄更大（67岁对62岁），纽约心脏协会心功能分级更差（III/IV级；36%对24%），既往HF住院次数更少（52%对61%）或心肌梗死发生率更低（30%对46%）；所有均<0.001。我们将有和无AF的患者分为5个NT-proBNP区间：<400、400至999（参考）、1000至1999、2000至2999和≥3000 pg/mL。对于心血管死亡或HF住院的主要复合结局，最低区间（<400 pg/mL）中有AF和无AF患者的事件发生率不同（每100患者年分别为8.2和5.0），但较高区间（400 - 999 pg/mL，每100患者年分别为7.4和7.7；1000 - 1999 pg/mL，每100患者年分别为9.8和11.4；2000 - 2999 pg/mL，每100患者年分别为13.5和13.4；≥3000 pg/mL，每100患者年分别为22.7和23.0）无差异。无论将NT-proBNP作为分类变量还是连续变量进行检查，以及在调整其他预后变量之前和之后，这些结果都是一致的。我们在复合结局的各个组成部分和全因死亡率方面也发现了类似结果。
射血分数降低的HF合并AF患者的NT-proBNP高于无AF患者。然而，在浓度高于400 pg/mL时（代表每组中的大多数患者），NT-proBNP对不良心血管结局具有相似的预测价值，与AF状态无关。
网址：https://www.clinicaltrials.gov。唯一标识符NCT00853658（ATMOSPHERE）和NCT01035255（PARADIGM-HF）。
