Interleukin-6 in Heart Failure With Reduced Ejection Fraction and the Effect of Dapagliflozin: An Exploratory Analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure Trial.

IF 10.3 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC. Heart failure Pub Date : 2025-02-26 DOI:10.1016/j.jchf.2024.12.012

Kieran F Docherty, Kirsty McDowell, Paul Welsh, Mark C Petrie, Inder Anand, David D Berg, Rudolf A de Boer, Lars Køber, Mikhail N Kosiborod, Felipe A Martinez, Eileen O'Meara, David A Morrow, Piotr Ponikowski, Marc S Sabatine, Naveed Sattar, Morten Schou, Ann Hammarstedt, Mikaela Sjöstrand, Anna Maria Langkilde, Pardeep S Jhund, Scott D Solomon, John J V McMurray

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引用次数: 0

Abstract

Background: Inflammation may play an important pathophysiological role in the development and progression of heart failure (HF). Interleukin (IL)-6 is a circulating cytokine and is the main regulator of the release of C-reactive protein (CRP).

Objectives: The authors examined the association between IL-6 and high-sensitivity (hs)-CRP and outcomes in patients with HFrEF in the DAPA-HF trial and their relationship with the effect of dapagliflozin.

Methods: Inclusion criteria included: 1) NYHA functional class II-IV; 2) left ventricular ejection fraction ≤40%; 3) elevated N-terminal pro-B-type natriuretic peptide; and 4) estimated glomerular filtration rate ≥30 mL/min/1.73 m². The primary outcome was a composite of a worsening HF event or cardiovascular death. IL-6 and hs-CRP were measured at baseline and 12 months (Roche Diagnostics). The associations between IL-6 and hs-CRP and outcomes were adjusted for known prognostic variables, including NT-proBNP.

Results: Among 2,940 patients, median IL-6 and hs-CRP at baseline were 6.01 pg/mL (Q1-Q3: 4.18-9.28 pg/mL) and 2.05 mg/L (Q1-Q3: 0.83-4.9 mg/L), respectively. Baseline IL-6 tertiles (T) were: T1 ≤4.72 pg/mL; T2 4.73-7.89 pg/mL; and T3 ≥7.90 pg/mL. The adjusted risks of the primary outcome relative to T1 were as follows: T2 = HR 1.34 (95% CI: 1.04-1.73) and T3 = HR 1.80 (95% CI: 1.41-2.31). A rise in IL-6 between baseline and 12 months was associated with worse outcomes. The beneficial effect of dapagliflozin on the primary outcome was consistent regardless of IL-6 concentration (continuous interaction P = 0.57), with similar results for hs-CRP. Dapagliflozin did not reduce IL-6 or hs-CRP at 12 months.

Conclusions: In DAPA-HF, elevated IL-6 and hs-CRP levels were each associated with the risk of worsening HF or cardiovascular death. Dapagliflozin reduced the risk of adverse outcomes regardless of baseline IL-6 or hs-CRP. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124).

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白细胞介素-6在心力衰竭伴射血分数降低及达格列净的作用：达格列净与心力衰竭试验不良后果预防的探索性分析

背景：炎症在心力衰竭（HF）的发生和发展中可能起着重要的病理生理作用。白细胞介素(IL)-6是一种循环细胞因子，是c反应蛋白（CRP）释放的主要调节因子。目的：在DAPA-HF试验中，作者研究了IL-6和高敏(hs)-CRP与HFrEF患者预后的关系，以及它们与达格列净疗效的关系。方法：纳入标准包括：1)NYHA功能等级II-IV；2)左室射血分数≤40%；3) n端前b型利钠肽升高；4)估计肾小球滤过率≥30 mL/min/1.73 m2。主要结局是心衰事件恶化或心血管死亡的综合结果。在基线和12个月时测量IL-6和hs-CRP（罗氏诊断）。根据已知的预后变量（包括NT-proBNP）调整IL-6和hs-CRP与预后之间的关系。结果：在2940例患者中，基线时IL-6和hs-CRP的中位数分别为6.01 pg/mL （Q1-Q3: 4.18-9.28 pg/mL）和2.05 mg/L （Q1-Q3: 0.83-4.9 mg/L）。基线IL-6分位数(T): T1≤4.72 pg/mL；T2 4.73 ~ 7.89 pg/mL；T3≥7.90 pg/mL。主要结局相对于T1的调整风险如下：T2 = HR 1.34 (95% CI: 1.04-1.73), T3 = HR 1.80 （95% CI: 1.41-2.31）。基线和12个月之间IL-6的升高与较差的结果相关。不管IL-6浓度如何，达格列净对主要结局的有益作用是一致的（持续相互作用P = 0.57）， hs-CRP的结果也相似。达格列净在12个月时没有降低IL-6或hs-CRP。结论：在DAPA-HF患者中，IL-6和hs-CRP水平升高均与HF恶化或心血管死亡的风险相关。无论基线IL-6或hs-CRP水平如何，达格列净均可降低不良结局的风险。达格列净对慢性心力衰竭患者心衰加重或心血管死亡发生率的影响研究[DAPA-HF]；NCT03036124)。

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来源期刊

JACC. Heart failure CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

21.20

自引率

2.30%

发文量

164

期刊介绍： JACC: Heart Failure publishes crucial findings on the pathophysiology, diagnosis, treatment, and care of heart failure patients. The goal is to enhance understanding through timely scientific communication on disease, clinical trials, outcomes, and therapeutic advances. The Journal fosters interdisciplinary connections with neuroscience, pulmonary medicine, nephrology, electrophysiology, and surgery related to heart failure. It also covers articles on pharmacogenetics, biomarkers, and metabolomics.