Reductions in N-Terminal Pro-Brain Natriuretic Peptide Levels Are Associated With Lower Mortality and Heart Failure Hospitalization Rates in Patients With Heart Failure With Mid-Range and Preserved Ejection Fraction
Reductions in N-Terminal Pro-Brain Natriuretic Peptide Levels Are Associated With Lower Mortality and Heart Failure Hospitalization Rates in Patients With Heart Failure With Mid-Range and Preserved Ejection Fraction
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DOI：
10.1161/circheartfailure.116.003105
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发表时间：
2016-11-01
影响因子：
9.7
通讯作者：
Lund, Lars H.
中科院分区：
文献类型：
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作者：
Savarese, Gianluigi;Hage, Camilla;Lund, Lars H.
背景：对于中等射血分数（HFmrEF）和保留射血分数（HFpEF）的心力衰竭，需要可行的替代终点进行II期试验。目的是评估在未选择的HFmrEF和HFpEF患者群体中，n端前b型利钠肽（NT-proBNP）的减少是否与死亡率/发病率的改善有关。方法和结果：在瑞典心力衰竭登记处，报告至少连续2次门诊NT-proBNP评估的HFmrEF （EF=40%-49%）和HFpEF （EF=50%）患者进行前瞻性研究。通过多变量Cox回归评估NT-proBNP降低与总死亡率、HF住院率及其组合之间的关系，NT-proBNP变化建模为二元（减少/增加）或限制性三次样条定量预测因子。在650例患者中，两次NT-proBNP测量间隔的中位时间为7个月，中位随访时间为1.65年，其中361例（55%）患者NT-proBNP降低，289例（45%）患者NT-proBNP升高。NT-proBNP的变化与预后风险相关。57名NT-proBNP降低的患者（16%）对78名NT-proBNP升高的患者（27%）死于任何原因（校正风险比=0.53；95%可信区间=0.36-0.77），61名（17%）对86名（30%）因心衰住院（风险比=0.41；95%可信区间=0.29-0.60），96名（27%）对125名（43%）报告了综合结果（风险比=0.46；95%可信区间=0.34-0.62）。这些发现分别在HFmrEF和HFpEF中得到了重复。结论：在常规护理期间的HFmrEF和HFpEF中，NT-proBNP的降低与死亡率和发病率的改善有关。需要研究NT-proBNP对治疗反应的变化是否能预测药物疗效。
Background-In heart failure with mid-range ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF), feasible surrogate end points are needed for phase II trials. The aim was to assess whether a reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with improved mortality/morbidity in an unselected population of HFmrEF and HFpEF patients.Methods and Results-In the Swedish Heart Failure Registry, HFmrEF (EF=40%-49%) and HFpEF (EF=50%) patients reporting at least 2 consecutive outpatient NT-proBNP assessments were prospectively studied. Associations between reduction in NT-proBNP and overall mortality, HF hospitalization, and their composite were assessed by multivariable Cox regressions, with NT-proBNP changes modeled as binary (decrease/increase) or quantitative predictor by restricted cubic splines. In 650 patients, at a median of 7 months between the 2 measurements of NT-proBNP and over a median followup of 1.65 years, 361 patients (55%) showed a reduction and 289 patients (45%) an increase in NT-proBNP. Change in NT-proBNP was associated with risk of outcomes. Fifty-seven patients (16%) who decreased their NT-proBNP versus 78 patients (27%) who increased it died from any cause (adjusted hazard ratio=0.53; 95% confidence interval=0.36-0.77), 61 (17%) versus 86 (30%) were hospitalized for HF (hazard ratio=0.41; 95% confidence interval=0.29-0.60), and 96 (27%) versus 125 (43%) reported the composite outcome (hazard ratio=0.46; 95% confidence interval=0.34-0.62). These findings were replicated in HFmrEF and HFpEF separately.Conclusions-In HFmrEF and HFpEF during routine care, decreases in NT-proBNP were associated with improved mortality and morbidity. Studies to determine whether NT-proBNP changes in response to therapy predict drug efficacy are needed.