DNA Repair in Patients With Stable Angina.

Study Overview
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Brief Summary
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Markers of DNA damage and repair are present in both atherosclerotic plaques and peripheral blood mononuclear cells of patients with coronary artery disease. A positive correlation has been observed between the level of DNA damage and the severity of atherosclerotic lesions, as well as atherogenic risk factors such as smoking, hypertension and hyperlipidaemia. A number of in-vitro studies have implicated defective DNA repair in the development and progression of atherosclerotic lesions. In mouse models of atherosclerosis, the DNA repair signalling cascade has been shown to be amenable to pharmacological intervention and overexpression of specific repair proteins attenuate the development of atherosclerotic plaques. However, data regarding the role of DNA repair in the pathogenesis of atherosclerosis in humans are lacking. We have preliminary data indicating reduced DNA repair activity in patients with stable angina. This study will determine the molecular basis and the biological consequences of this observation.

Official Title
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DNA Repair in Patients With Stable Angina.

Conditions
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Coronary Artery Disease, Coronary Arteriosclerosis, DNA Damage, DNA Repair Abnormality

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Ability to provide written informed consent Exclusion Criteria: Age ≥ 80 years Inability to provide written informed consent Presentation with an acute coronary syndrome Severe valvular heart disease Hypertrophic cardiomyopathy Left ventricular ejection fraction ≤ 35% Prior coronary revascularisation (surgical or percutaneous) Diabetes Mellitus Clinical evidence of peripheral vascular disease Prior history of cerebrovascular disease Malignancy Active inflammatory disorders (e.g. rheumatoid arthritis/connective tissue disorder) Renal impairment eGFR <60ml/min/1.73m2 Anaemia (Hb <100g/dL)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patient Arm.<br>Consecutive patients undergoing elective percutaneous coronary intervention (PCI) or isolated coronary artery bypass grafting (CABG) for symptomatic stable angina (SA) despite optimal medical therapy at the University Hospital Southampton NHS Foundation Trust will be prospectively enrolled (n=86). No interventions administered. 40ml of whole blood in EDTA vials to be taken for cellular separation and analysis. | |
| Age and gender matched controls<br>Age and gender-matched patients being investigated for chest pain with unobstructed coronary arteries, defined as coronary stenosis ≤ 30% in any major epicardial vessel on CT or invasive coronary angiography, will also be recruited as controls (n=86). 40ml of whole blood in EDTA vials to be taken for cellular separation and analysis. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association between monocytes exhibiting reduced base excision repair and/or double strand break repair activity in patients with stable angina as compared to patients without coronary artery disease. | This will be assessed using real-time polymerase chain reaction, western blotting and proteosomal degradation assay. | Blood will be collected at the time of hospital admission for index procedure. No follow-up of patients will be required. | 
| Reduced DNA repair activity is associated with impaired response to oxidative stress in human monocytes in patients with stable angina in comparison to an age and gender matched control. |  | Blood will be collected at the time of hospital admission for index procedure. No follow-up of patients will be required. |