Is There an Association Between Non-cardiac Inflammatory Conditions and Dynamic Changes in Platelet Priming & Reactivity? A Prospective Observational Single Centre Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 100
- 主要终点
- Dynamic platelet reactivity with non-cardiac inflammation
研究概览
简要总结
Non-cardiac acute and chronic inflammatory conditions are associated with high risk of acute myocardial infarction.
Specifically, there are reports of high prevalence of AMI and cardiac death in chronic conditions such as Rheumatoid arthritis, chronic gum disease, psoriasis and Chronic airway disease. Furthermore, there are intriguing temporal links between acute non-cardiac conditions, including fractured neck of femur and admission for chest infection in the elderly and subsequent risk of AMI within the next few weeks. Finally, a more recent association has been reported between COVID vaccination and acute thrombotic events.
In Summary, a link between acute non-cardiac inflammatory conditions and subsequent AMI in a near term envelope is established, but unexplained, and circumstantial evidence so far suggests a possible mechanism in terms of dynamic alteration in platelet reactivity. It is this concept we wish to explore further in the proposed set of experiments.
Our experiments may provide some insight into a potential mechanism of such an association, which could have implications for future tailored therapeutic interventions.
We will recruit 5 groups of patients, consistent with the data produced previously and the literature regarding disease models of non-cardiac inflammations. Aiming to recruit 20 patients per group with 100 candidates in total. Groups including:
- Fracture neck of femur.
- Patients >70 years age admitted with chest infection.
- Healthy volunteers receiving fourth COVID booster vaccine.
- Patients admitted with AMI within 6 weeks of (fractured neck of femur, chest infection Rheumatoid arthritis flare up, exacerbation of psoriasis and exacerbation of inflammatory bowel disease).
- AMI secondary to stent thrombosis.
Study will be undertaken within the Cardiothoracic unit at University Hospital Southampton, the sponsor will be UHS Research and Development Department, UHS.
详细描述
BACKGROUND
Inflammation and Platelets
Cardiovascular disease (CVD) is the leading cause of death worldwide. Specifically, acute myocardial infarction (AMI) and acute ischaemic stroke are common causes of morbidity and mortality and are responsible for substantial healthcare costs. Whilst the underlying pathophysiology of atherosclerosis is now better understood as a chronic inflammatory process, the exact precipitants for the acute inflammation responsible for the acute event are still not fully explained. It has become clear that platelets play a key role in the pathophysiology of both atheroma formation and acute thrombus formation in AMI and stroke. Specifically, platelet activation is an integral component of initiation and amplification of the local vascular inflammatory response in these conditions. It is for this reason that routine antiplatelet therapy represents a mainstay of treatment for patients with coronary atheroma and especially for those treated with intracoronary stents.
Evidence for inter- and intra-individual variability in response to antiplatelets: dynamic reactivity
However, previous work from our group and others indicates that the response of individuals to both aspirin and P2Y12 inhibitors is idiosyncratic, so that some individuals may be relatively resistant to aspirin as well as clopidogrel, prasugrel and ticagrelor. Specifically, we have previously shown that patients on P2Y12 inhibitors for coronary stents with high on treatment platelet reactivity have elevated risk of stent thrombosis , and that individual responses can be modified using tailored therapy. Furthermore, our group has previously shown that the response to both aspirin and P2Y12 inhibitors is dynamic. Thus, there is a rebound Adenosine Diphosphate (ADP) response after clopidogrel is withdrawn in patients with drug-eluting stents. With regard to aspirin responses, we have reported that the response to arachidonic acid stimulation is variable within individuals, has some interaction with P2Y12 inhibitors, and that there appears to be a cyclo-oxygenase-dependent and -independent pathway for AA-induced platelet activity. Our previous data also suggest that the most commonly used near patient VerifyNow platelet test overestimates the response of patients to clopidogrel.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients over 18 years of age.
- •Indication for inclusion:
- •Group 1 fractured neck of femur Group 2 age >70yrs with chest infection Group 3 healthy volunteers receiving COVID booster dose Group 4 Acute myocardial infarction within 6 weeks from suffering (Fracture neck of femur, chest infection, rheumatoid arthritis flare-up, Psoriasis flare up or flare up of inflammatory bowel disease).
- •Group 5 Acute myocardial infarction secondary to stent thrombosis.
- •Written Informed Consent to participate in the study.
- •Antiplatelet Naïve on admission, except for Groups 4 & 5.
排除标准
- •Surgery in an emergency setting.
- •Liver failure. (From history and background, deranged Liver functions tests i.e AST/ALT)
- •Renal failure requiring dialysis.
- •Platelet count <150,
- •Medications including steroids, anticoagulants, non-steroidal anti-inflammatory drugs, COX-inhibitors.
- •Known malignancy.
- •Pregnancy.
结局指标
主要结局
Dynamic platelet reactivity with non-cardiac inflammation
时间窗: During the period of recruitment (Max 1 month for each patient)
Detecting an association between dynamic platelet reactivity and vascular inflammatory status in a variety of non-cardiac inflammatory conditions
次要结局
未报告次要终点