DNA Repair in Patients With Stable Angina. (DECODE II)

University Hospital Southampton NHS Foundation Trust

Status: Enrolling

Conditions: Coronary Artery Disease; Coronary Arteriosclerosis; DNA Repair Abnormality; DNA Damage

Study type: Observational

Funder types: Other

Identifiers

NCT04453267

CAR0566

Details and patient eligibility

About

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.

Enrollment: 172 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

172 participants in 2 patient groups

Patient Arm.

Description:

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

Description:

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.