Prospective Evaluation of Acetyl-Coenzyme A Carboxylase Phosphorylation State in Platelets in Atherothrombotic Coronary Artery Disease.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 188
- 试验地点
- 2
- 主要终点
- an increase in platelet ACC phosphorylation state in patients with coronary artery disease
研究概览
简要总结
In human purified platelets, only thrombin, and not the other platelet agonists, leads to a transient activation of the protein kinase activated by AMP (AMPK) and to phosphorylation of its "bona fide" substrate, ACC on its Ser79. ACC phosphorylation (P-ACC) can be an interesting marker of thrombin action on platelets. Indeed platelet and coagulation interplay, though undoubtedly present in atherosclerosis and atherothrombosis, remains difficult to assess. Our group showed that atherosclerotic mice (SRBI/Apolipoprotein E knock-out) had higher platelet P-ACC compared to corresponding control mice (C57BL6). In agreement with these data, preliminary results showed increased platelet P-ACC in a small cohort of patients admitted for coronary angiogram, with demonstrated coronary artery disease (CAD).
In the light of our preliminary results, we sought to analyze platelet P-ACC in a large prospective clinical trial (ACCTHEROMA) in patients admitted for coronary angiogram. The aim of the study is to compare platelet P-ACC in platelets of patients with CAD and more particularly in unstable CAD patients to non-CAD patients. This study could potentially identify patients at high risk of future ischemic cardiovascular events, because of a higher level of thrombin generation.
详细描述
Consecutive patients with planned coronary angiogram at the Cliniques Universitaires Saint Luc, Brussels, whatever the indication, will be included between March 2015 and February 2016. Informed consent will be obtained before angiogram.
A. Blood Sampling Routine veinous blood sample will be done under fasting condition in the cardiology ward before the angiogram (standard of care for patients undergoing coronary angiogram).
In order to avoid additional puncture for blood sampling and to limit platelet activation, blood samples are withdrawn after sheath insertion at the Cath lab before any drug administration. The following measurements will be done:
- Routine coagulation tests including international rationalize ratio, activated cephaline time, thrombin time, prothrombin time, Fibrinogen, DDimers.
- Platelet reactivity testing by the Multiple Electrode Aggregometer (Multiplate Analysis)
- Platelet isolation and lysates will be stocked frozen for phospho-protein analysis by immunoblotting and electrochemiluminescence (ECLIA)
- Aliquots of poor platelet plasma stocked frozen for inflammation (HsCRP), thrombin generation tests (thrombin-antithrombin complex, prothrombin fragment F1.2, endogenous thrombin generation potential-ETP), platelet activation markers (platelet factor 4, soluble CD40ligand, soluble P-selectin) and circulating micro-RNA extraction.
- Platelet isolation and further purification for platelet specific micro-RNA extraction.
B. Atherosclerosis evaluation All patients underwent coronary angiogram. Significant coronary artery lesion is defined as a luminal stenosis above 50%. Syntax score will be calculated for all patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Screening
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Signed informed consent
- •Planned angiography within the next 3 days, whatever the indication.
排除标准
- •Not able to sign informed consent
- •Patients on anticoagulation therapy (oral or parenteral) including heparins, fondaparinux, vitamin K antagonist, novel oral anticoagulants, for any reasons.
- •Active neoplasia
- •Active inflammatory disease
- •Patients with life expectancy lower than 3 years
- •Haemophilia and other coagulopathy
- •Abnormal platelet count
- •Heart transplanted patients
- •Active hepatitis B or C or HIV patients
- •Any contra-indication for coronary angiography.
结局指标
主要结局
an increase in platelet ACC phosphorylation state in patients with coronary artery disease
时间窗: 2 years
次要结局
- a correlation between thrombin generation markers and platelet P-ACC in overall population.(2 years)
- platelet ACC phosphorylation state according clinical severity of CAD (stable versus unstable patients)(2 years)
- the role of platelet P-ACC in predicting the risk of the patient for future cardiovascular events (death, myocardial infarction, stroke)(3 years)