Question: Are concentrations of novel circulating biomarkers of high risk coronary plaque associated with long-term cardiovascular outcomes in patients within UK Biobank?
Rationale: High-sensitivity cardiac troponin assays have transformed the evaluation of patients in the Emergency Department with suspected myocardial infarction, and today the majority of patients can be safely discharged with myocardial infarction ruled-out. However, future cardiovascular risk is not equal in all discharged patients. In contrast to those with the lowest troponin concentrations, patients with intermediate troponin concentrations between 5 ng/L and the 99th centile upper reference limit are 10-times more likely to have an adverse cardiovascular event at 1 year. Unstable or vulnerable atherosclerotic coronary disease is a prerequisite for myocardial infarction, and it is thought that troponin could be identifying unstable coronary disease in these patients. However, troponin is poorly specific for coronary disease. The ability to identify vulnerable coronary plaque with high-certainty using a blood test and then target novel disease modifying therapies to prevent myocardial infarction would represent a major advance for the millions of patients every year who present to hospital with suspected acute coronary syndrome.
Progress to date: In patients enrolled in the PRECISE-CTCA trial having coronary imaging with Computed Tomography Coronary Angiography (CCTA), plaque characterisation was performed and stored blood evaluated for novel circulating protein biomarkers using the Olink Cardiovascular and Inflammatory panels. External validation was then performed in the WESTCOR study. Of 734 candidate biomarkers analysed, several have been identified as having high statistical probability of an association with high risk plaque features on CCTA. Further large scale validation of these biomarkers is now required in to determine association with future adverse cardiovascular events.
