可溶性尿激酶纤溶酶原激活剂受体和HFpEF的预后:一项TOPCAT辅助研究。

IF 3.7 2区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Christina G Hutten, Annika Tekumulla, Anis Ismail, Alexi Vasbinder, Theresa Farhat, Pennelope Kunkle, Sascha N Goonewardena, Ahmed Abdel-Latif, Bertram Pitt, Salim S Hayek
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引用次数: 0

摘要

目的:炎症被认为是保留射血分数(HFpEF)心力衰竭的关键致病机制。可溶性尿激酶纤溶酶原激活剂受体(suPAR)是先天免疫活性的调节因子,与心力衰竭的发生有关;然而,它在HFpEF中的作用仍不清楚。我们的目的是阐明suPAR在HFpEF结局中的作用。方法:在这项对TOPCAT试验北美队列的二次分析中,在接受内酯或安慰剂治疗的HFpEF患者亚组(n = 406)中,在基线和1年测量suPAR。我们评估了suPAR水平与不良结局之间的关系,螺内酯是否影响suPAR水平,以及螺内酯与结局之间的关系是否依赖于suPAR水平。主要结局是心血管死亡、心脏骤停或因心力衰竭住院治疗的综合结果。结果:参与者平均年龄69.5岁,女性占46.6%。中位随访2.9年后,19.9%的患者出现了主要结局事件。suPAR浓度最高的各组(≤3.93 ng/mL)主要结局的5年累积发生率为44%,而浓度最低的各组(≤2.94 ng/mL)的5年累积发生率为14% (P = 0.001)。螺内酯在1年时没有显著改变suPAR水平,其对结果的影响也没有被基线suPAR所改变(相互作用的P = 0.6)。在多变量分析中,基线suPAR水平每增加一倍,主要结局风险增加近两倍,与传统危险因素和利钠肽(NP)水平无关(HR 1.94 [95% CI 1.33-2.83])。suPAR的风险识别能力优于NP,具有可叠加性。结论:虽然suPAR水平独立预测HFpEF患者的不良预后,但螺内酯不能调节这种炎症途径。研究结果表明,suPAR在HFpEF中是一种稳定的炎症生物标志物,强调需要进一步评估该人群的靶向抗炎策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Soluble urokinase plasminogen activator receptor and outcomes in HFpEF: A TOPCAT ancillary study.

Aims: Inflammation is postulated to be a key pathogenic mechanism in heart failure with preserved ejection fraction (HFpEF). Soluble urokinase plasminogen activator receptor (suPAR), a regulator of innate immune activity, is associated with incident heart failure; however, its role in HFpEF remains unclear. We aimed to elucidate the role of suPAR in HFpEF outcomes.

Methods: In this secondary analysis of the TOPCAT trial's North American cohort, suPAR was measured at baseline and 1 year in a subset of patients with HFpEF (n = 406) treated with either spironolactone or placebo. We assessed the association between suPAR levels and adverse outcomes, whether spironolactone influenced suPAR levels and whether the association between spironolactone and outcomes is dependent on suPAR levels. The primary outcome was a composite of cardiovascular death, cardiac arrest or hospitalization for heart failure management.

Results: The mean age of participants was 69.5 years, and 46.6% were female. After a median follow-up of 2.9 years, 19.9% experienced the primary outcome event. The 5-year cumulative incidence of the primary outcome in the highest tertile of suPAR (>3.93 ng/mL) was 44%, compared with 14% in the lowest tertile (≤2.94 ng/mL) (P = 0.001). Spironolactone did not significantly change suPAR levels at 1 year, nor was its effect on outcomes modified by baseline suPAR (P for interaction = 0.6). In multivariable analysis, each doubling of baseline suPAR levels was associated with nearly twofold increased risk of the primary outcome, independent of traditional risk factors and natriuretic peptide (NP) levels (HR 1.94 [95% CI 1.33-2.83]). suPAR's risk discrimination ability was superior and additive to that of NP.

Conclusions: While suPAR levels independently predict poor outcomes in HFpEF patients, spironolactone does not modulate this inflammatory pathway. The findings suggest that suPAR represents a stable inflammatory biomarker in HFpEF, highlighting the need for further evaluation of targeted anti-inflammatory strategies in this population.

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来源期刊
ESC Heart Failure
ESC Heart Failure Medicine-Cardiology and Cardiovascular Medicine
CiteScore
7.00
自引率
7.90%
发文量
461
审稿时长
12 weeks
期刊介绍: ESC Heart Failure is the open access journal of the Heart Failure Association of the European Society of Cardiology dedicated to the advancement of knowledge in the field of heart failure. The journal aims to improve the understanding, prevention, investigation and treatment of heart failure. Molecular and cellular biology, pathology, physiology, electrophysiology, pharmacology, as well as the clinical, social and population sciences all form part of the discipline that is heart failure. Accordingly, submission of manuscripts on basic, translational, clinical and population sciences is invited. Original contributions on nursing, care of the elderly, primary care, health economics and other specialist fields related to heart failure are also welcome, as are case reports that highlight interesting aspects of heart failure care and treatment.
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