Immuno-haemostatic dysregulation in heart failure with preserved ejection fraction

IF 3.7 2区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Giorgia D'Italia, Daniëlle M. Coenen, Titus P. Lemmens, Lloyd Brandts, Simone J. H. Wielders, Magdolna Nagy, Sanne G. J. Mourmans, Anouk Achten, Ahmad Al-Abadi, Jerremy Weerts, Arantxa Barandiaran Aizpurua, Vanessa van Empel, Blanche Schroen, Judith M. E. M. Cosemans
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引用次数: 0

Abstract

Aims

Heart failure with preserved ejection fraction (HFpEF) is a complex condition with partially unclear pathophysiology, in which systemic inflammation is a central contributor to changes in cardiac structure and function. The contribution of non-traditional immune effectors—such as platelets and coagulation—remains underexplored in HFpEF. We characterized platelet function, as well as coagulation and neutrophil activation, in patients with HFpEF.

Methods

The in vivo activation of platelets, neutrophils, endothelial cells and coagulation was measured in plasma from patients with HFpEF (n = 103), age- and sex-matched controls (n = 40) and pooled plasma from a healthy reference cohort. Flow cytometric and microfluidic assays were performed to investigate platelet function ex vivo.

Results

Compared with matched controls, patients with HFpEF exhibited reduced platelet reactivity, characterized by alterations in platelet integrin activation and granule release, and an overall decrease in thrombus activation, contraction and fibrin formation. In vivo platelet activation markers β-TG and CXCL4 were increased in plasma from patients with HFpEF and matched controls compared with the healthy reference cohort (β-TG: 923.01 and 822.25 vs. 335.06 ng/mL; CXCL4: 660.16 and 603.63 vs. 458.34 ng/mL). Linear regression analyses showed an association between platelet aberrant activation and function and the presence of HFpEF, independent of comorbidities or medications [e.g., thrombus characteristics (size, contraction, height): P valuesFully adjusted model = <0.001; <0.001; <0.001]. Patients with HFpEF showed higher levels of the neutrophil activation markers MPO and S100A8/A9 compared with matched controls (MPO: P value = 0.0152; S100A8/A9: P value = 0.0041). Levels of endothelial markers ICAM-1 and VCAM-1 were unaltered between groups. Coagulation was found elevated in patients with HFpEF, particularly in patients not on anticoagulant (AC) medications, showing increased plasma levels of plasma kallikrein, factor XI, factor IX, thrombin and D-dimer (kallikrein: P value = 0.0415; AC excluded: FXIa:C1inh: P value = 0.0110; FIXa:AT: P value = 0.0095; T:AT: 4.46 vs. reference 4 μg/L; D-dimer: 0.65 vs. reference 0.5 mg/L).

Conclusions

Patients with HFpEF present with dysfunctional platelets, a procoagulant state and neutrophil activation. The association of immuno-haemostatic processes including aberrant platelet function with the presence of HFpEF, independent of comorbidities or medications, suggests that platelet dysfunction is an intrinsic feature of HFpEF.

Abstract Image

保留射血分数的心力衰竭患者的免疫-止血功能失调。
目的:保留射血分数的心力衰竭(HFpEF)是一种复杂的疾病,其部分病理生理尚不清楚,其中全身炎症是心脏结构和功能改变的主要因素。非传统免疫效应(如血小板和凝血)在HFpEF中的作用仍未得到充分探讨。我们对HFpEF患者的血小板功能、凝血和中性粒细胞活化进行了研究。方法:检测HFpEF患者(n = 103)、年龄和性别匹配的对照组(n = 40)和健康对照队列血浆中血小板、中性粒细胞、内皮细胞和凝血功能的体内活化情况。用流式细胞术和微流体法观察体外血小板功能。结果:与对照组相比,HFpEF患者血小板反应性降低,表现为血小板整合素活化和颗粒释放改变,血栓活化、收缩和纤维蛋白形成总体减少。与健康对照组相比,HFpEF患者和匹配对照组血浆中血小板活化标志物β-TG和CXCL4升高(β-TG: 923.01和822.25 vs. 335.06 ng/mL;CXCL4: 660.16和603.63 vs. 458.34 ng/mL)。线性回归分析显示,与合并症或药物(如血栓特征(大小、收缩、高度))无关,血小板异常活化和功能与HFpEF存在关联:P值。完全调整模型=结论:HFpEF患者存在血小板功能障碍、促凝状态和中性粒细胞活化。包括异常血小板功能在内的免疫-止血过程与HFpEF存在的关联,独立于合并症或药物治疗,表明血小板功能障碍是HFpEF的内在特征。
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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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