Improving risk stratification in atherosclerotic disease Circulating biomarkers: The holy grail or a mythic battle?

Risk prediction in cardiovascular disease is an ongoing work in progress: researchers continue to seek new risk factors that can predict cardiovascular events or that can be incorporated into risk assessment algorithms. In the current era of risk-tailored and personalized cardiovascular care, assessment of cardiovascular risk in individuals is an integral part of clinical decision making. Risk prediction can be applied in various clinical domains. The overall aim of this thesis is to improve risk stratification of patients with atherosclerotic disease focusing on carotid artery disease and coronary artery disease (CAD). Part I describes biomarkers in plasma and in plasma extracellular vesicles that are associated with major adverse cardiovascular events (MACE) in patients following carotid endarterectomy (CEA). Due to the considerably high residual risk of MACE after CEA, intensified secondary prevention therapy is recommended in this population. In order to balance the health-related costs and associated benefits of intensified secondary prevention in CEA patients, detailed risk stratification using blood based biomarkers is of key importance. Part II assesses the value of extracellular vesicle proteins as diagnostic biomarkers for CAD (Chronic Coronary Syndrome and Unstable Angina). Early recognition of CAD is important as lifestyle adjustments, pharmacological therapies and invasive interventions can modify the risk for progression to Acute Coronary Syndrome. However, currently a large number of patients is unnecessary referred for additional diagnostic testing. EV-associated markers could improve the risk stratification before referral and decrease the burden for patients and the health care system.