Endotoxemia in Coronary Thrombus of Patients With Acute Coronary Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- LPS in blood of STEMI, SA patients and controls.
研究概览
简要总结
Platelets play a key role in the athero-thrombotic process. However, the in vivo mechanism accounting for thrombus growth at site of coronary atherosclerotic lesion has not been fully elucidated. While platelet adhesion and aggregation on the thrombogenic core of atherosclerotic plaque is an established mechanism for thrombus growth, the role of systemic factors, which may contribute to thrombus via amplification and propagation of platelet aggregation, is still to be clarified.
There is a growing body of evidence that lipopolysaccharides (LPS), are implicated in athero-thrombosis. Circulating levels of endotoxins have been associated with human atherosclerosis progression, particularly in smokers or in patients with infections. Furthermore, endotoxins seem to be implicated in the thrombotic process through several mechanisms including up-regulation of macrophage tissue factor expression and amplification of platelet response upon interaction with Toll-like receptor 4. The relationship between endotoxins and platelets may be relevant in the context of acute coronary syndromes as endotoxins could locally amplify platelet-derived thrombus growth but this issue is still unexplored.
Previous studies demonstrated that low-grade endotoxemia is detectable in human circulation, likely as consequence of enhanced gut permeability, and may be responsible for leucocyte-platelet aggregate and eventually thrombosis. The investigators hypothesize that low-grade endotoxemia may be observed in patients with coronary heart disease and may favor, at site of coronary unstable plaque, thrombus growth. To explore this issue, Escherichia Coli (EC)-LPS concentration and biomarkers of platelet activation will be measured in coronary thrombus and intra-coronary blood of patients with STEMI and stable angina (SA), respectively, and in peripheral circulation of both patients and controls. EC DNA will be searched in serum of all patients by polymerase chain reaction (PCR). Furthermore, to substantiate that LPS could be biologically active, immune-histochemical analysis of thrombi and in vitro studies will be performed to assess the interplay between LPS and platelet activation.
详细描述
In this case-control study, three groups of patients will be compared: consecutive STEMI patients undergoing to manual thrombo-aspiration during primary percutaneous coronary intervention, patients with chronic stable angina (SA) undergoing elective diagnostic and/or interventional coronary procedure and outpatients without coronary heart disease referring to the ambulatory of the Department of Internal Medicine, I Clinica Medica, Sapienza -University of Rome.
Patients will be recruited from three Centers: i) Department of the Heart and Great Vessels "Attilio Reale", Sapienza -University of Rome; ii) Department of Internal Medicine, I Clinica Medica, Sapienza -University of Rome; iii) Department of Interventional Cardiology, Santa Maria University Hospital, Terni.
The study complied with the Declaration of Helsinki and was approved by the local ethic committees of centers involved.
In patients presenting STEMI, coronary thrombi, when present, or plaque fragments will be aspirated from the culprit coronary artery before stent implantation and collected in EDTA tubes.
Thrombi will be homogenized in 5 mL of a homogenization buffer. Aliquots of thrombi homogenate will be centrifuged. In a subset of STEMI patients, part of the thrombotic material aspirated will be fixed in 4% buffered formaldehyde for histologic and immunohistochemical analyses.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 95 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For STEMI patients:
- •diagnosis of STEMI based on the current European Guidelines
- •For SA patients:
- •diagnosis of SA defined according to the European Guidelines as lack of episodes of coronary instability for at least 6 months prior to admission
- •For control subjects:
- •outpatients without diagnosis of coronary heart disease
排除标准
- •estimated glomerular filtration rate less than 30 ml/min/m2
- •acute or recent systemic infections (3 weeks)
- •treatment with systemic corticosteroids
- •treatment with oral anticoagulants
- •malignancy
- •lack of consent to participate
- •Additional exclusion criteria for STEMI patients were symptoms duration>12 h, rescue PCI, in-stent thrombosis and anatomical difficulty in reaching the lesion.
结局指标
主要结局
LPS in blood of STEMI, SA patients and controls.
时间窗: 1 year
LPS will be measured in serum and expressed as concentration (pg/ml)
次要结局
- LPS in thrombus and intra-coronary blood of STEMI and SA patients.(1 year)
- sP-selectin in thrombus and intra-coronary blood of STEMI and SA patients.(1 year)
- Zonulin in blood of STEMI, SA patients and controls(1 year)
- sCD40L in thrombus and intra-coronary blood of STEMI and SA patients.(1 year)
- Escherichia coli-DNA(1 year)
- Histologic and immunohistochemical analyses of thrombus fragments aspirated from a subset of STEMI patients.(1 year)
- HS-CRP in blood of STEMI, SA patients and controls(1 year)
- Soluble CD40L (sCD40L) in blood of STEMI, SA patients and controls.(1 year)
- sP-selectin in blood of STEMI, SA patients and controls.(1 year)
研究者
Francesco Violi
Director, Head of Internal Medicine, Clinical Professor
University of Roma La Sapienza