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高血小板肾上腺素能活性及垂体/髓质轴的伴随激活作为急性冠脉综合征幸存者的警示实验室参数——应激性心肌梗死研究

High platelet adrenergic activity and concomitant activation of the pituitary/medullar axis as alarming laboratory parameters in ACS survivors-the STRESS-AMI study.

作者信息

Gulyás Zalán, Horváth Zsófia, Hajtman László, Kovács Andrea, Kohut László, Kósa István, Tóth-Zsámboki Emese, Kiss Róbert Gábor

机构信息

Department of Cardiology, Central Hospital of Northern Pest-Military Hospital, Budapest, Hungary.

Cardiac Rehabilitation Institute, Central Hospital of Northern Pest-Military Hospital, Balatonfüred, Hungary.

出版信息

Front Cardiovasc Med. 2024 Feb 21;11:1338066. doi: 10.3389/fcvm.2024.1338066. eCollection 2024.

Abstract

INTRODUCTION

Kinetics of stress-related biological parameters were determined in acute coronary syndrome (ACS) patients undergoing complex cardiovascular rehabilitation.

METHODS

We determined platelet functionality in the absence/presence of a selective alpha-2 adrenergic receptor inhibitor, atipemazole parallel with salivary cortisol levels at enrolment, and at 3- and 12-months follow-up in 75 ACS patients with percutaneous coronary intervention.

RESULTS

Pharmacological/non-pharmacological secondary prevention methods have been efficiently applied. Baseline aggregometry indicated platelet hyperactivity, decreasing gradually and being significantly reduced late, at 12 months ( < 0.05). Cortisol levels followed similar kinetics ( < 0.05). Baseline epinephrine-induced aggregations (EIA) significantly correlated with most of the other platelet agonists, even at subsequent time-points. Patients with upper-quartile EIA at enrolment (EIA-UQ) had significantly higher ADP- and collagen-induced aggregations at enrolment, at 3- and 12-months follow-up as well, indicating that high adrenergic response in the acute phase is accompanied by general platelet hyperactivity and predicts sustained platelet activation. In the EIA-UQ group higher cardiac biomarker release, elevated C-reactive protein and cortisol levels, and lower baseline left ventricular ejection fraction were detected.Atipemazole significantly reduced platelet aggregation induced by several platelet agonists, being most potent and comparable to full P2Y inhibition on collagen-induced aggregations ( < 0.05), indicating that catecholamines might serve as promt/long-term modulators of platelet function.

DISCUSSION

Despite effective CCR programme and dual antiplatelet therapy, prolonged activation of sympathetic neuroendocrine system and general platelet hyperactivity can be detected up to one year in ACS patients with high adrenergic platelet activity. Moreover, initial high adrenergic activity is accompanied by clinical parameters associated to increased cardiovascular risk, therefore early identification of these patients might support complex optimal long-term therapy.

摘要

引言

在接受复杂心血管康复治疗的急性冠状动脉综合征(ACS)患者中测定了应激相关生物学参数的动力学。

方法

我们在75例接受经皮冠状动脉介入治疗的ACS患者中,在入组时以及3个月和12个月随访时,测定了在存在/不存在选择性α-2肾上腺素能受体抑制剂阿替派唑的情况下的血小板功能,并同时测定了唾液皮质醇水平。

结果

已有效应用药物/非药物二级预防方法。基线聚集试验表明血小板活性过高,其活性逐渐降低,并在12个月时显著降低(<0.05)。皮质醇水平呈现相似的动力学变化(<0.05)。基线肾上腺素诱导的聚集(EIA)与大多数其他血小板激动剂显著相关,即使在后续时间点也是如此。入组时EIA处于上四分位数(EIA-UQ)的患者在入组时、3个月和12个月随访时,ADP和胶原诱导的聚集也显著更高,这表明急性期的高肾上腺素能反应伴随着一般血小板活性过高,并预示着血小板的持续活化。在EIA-UQ组中,检测到更高的心脏生物标志物释放、升高的C反应蛋白和皮质醇水平,以及更低的基线左心室射血分数。阿替派唑显著降低了几种血小板激动剂诱导的血小板聚集,在胶原诱导的聚集中作用最强且与完全P2Y抑制作用相当(<0.05),表明儿茶酚胺可能作为血小板功能的即时/长期调节剂。

讨论

尽管有有效的心血管康复计划和双联抗血小板治疗,但在肾上腺素能血小板活性高的ACS患者中,交感神经内分泌系统的长期激活和一般血小板活性过高在长达一年的时间内仍可被检测到。此外,初始的高肾上腺素能活性伴随着与心血管风险增加相关的临床参数,因此早期识别这些患者可能有助于进行复杂的最佳长期治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3829/10914969/957b396e6659/fcvm-11-1338066-g001.jpg

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