Multimodal Biomarkers in Coronary Artery Disease Pathogenesis: The Oxford Acute Myocardial Infarction Study (OXAMI Study)

Coronary artery disease is one of the most common causes of illness and death. It develops when fatty deposits, known as plaques, build up in the arteries that supply blood to the heart. These plaques can gradually narrow the arteries and reduce blood flow, causing symptoms such as chest pain (angina). Sometimes a plaque can suddenly break open, causing a blood clot to form and block the artery. This can lead to a heart attack and permanent damage to the heart muscle.

Although much has been learned about coronary artery disease, important questions remain about why some plaques suddenly become unstable, how this affects blood flow through the smallest blood vessels of the heart, and why some patients develop more heart muscle damage than others.

The Oxford Acute Myocardial Infarction (OxAMI) research programme aims to improve our understanding of these processes. We will study both the disease within the coronary arteries (the "upstream" problem) and its effects on the heart muscle (the "downstream" damage). By examining these together, we hope to understand more clearly how changes in coronary plaques lead to heart injury and how this differs between patients.

Patients undergoing procedures to investigate or treat coronary artery disease provide an important opportunity to study these processes. During coronary angioplasty (also called percutaneous coronary intervention or PCI), a narrow or blocked artery is opened, usually using a small balloon and a stent. This procedure can disturb the underlying plaque in a similar way to the plaque disruption that occurs during a heart attack. Where appropriate, we may therefore collect blood and material released from the plaque during these procedures. Blood may be collected from different locations in the circulation, allowing us to study substances released by the plaque and heart muscle. Material that would otherwise be discarded during treatment may also be collected for laboratory analysis.

We will use several established and newer techniques to examine the coronary arteries, the small blood vessels within the heart, and the heart muscle. These may include detailed imaging from inside the coronary arteries using intravascular ultrasound (IVUS) or optical coherence tomography (OCT). We may also measure blood pressure and flow within the coronary arteries to assess how well the small blood vessels supplying the heart are working.

Non-invasive heart scans may include cardiovascular magnetic resonance (CMR/MRI), cardiac computed tomography (CT) and echocardiography (ultrasound). These techniques can provide detailed information about the structure and function of the heart, blood supply to the heart muscle, areas of injury or permanent scarring, and changes that occur following a heart attack. In particular, MRI may help distinguish heart muscle that has been permanently damaged from muscle that is injured but could potentially recover after blood flow is restored. This may be especially important for patients who arrive at hospital several hours after their heart attack began.

Other measurements may include electrocardiograms (ECGs), which record the electrical activity of the heart, and measurements of heart pressure, volume and function. Some participants may also have longer-term ECG monitoring.

Blood and tissue samples may be analysed using a range of laboratory techniques. These studies will investigate inflammation, blood clotting and other biological processes involved in coronary artery disease and heart attacks. Newer laboratory methods may allow us to measure large numbers of proteins and small molecules in the blood. Material collected from plaques may also be examined under a microscope to identify its cells and structural components.

With additional consent, blood samples may be stored for genetic research. This could help us understand whether differences in people's genes influence their risk of coronary artery disease, their response to a heart attack, or the amount of heart damage that occurs.

By combining information about coronary plaques, blood flow through the heart's circulation, heart muscle injury, imaging, blood and tissue markers, and genetic factors, OxAMI aims to build a detailed picture of coronary artery disease and heart attacks. The programme will establish a carefully characterised group of research participants who may contribute to future OxAMI studies conducted under separate research protocols.

Ultimately, this research aims to identify better ways to predict, diagnose and understand coronary artery disease and heart attacks, and to identify new approaches that could improve treatment and outcomes for future patients.