Soluble Urokinase‐Type Plasminogen Activator Receptor: A Useful Biomarker for Coronary Artery Disease and Clinical Outcomes?

While coronary artery disease (CAD) is a leading cause of death and disability worldwide, causal pathways for the progression of underlying atheromatous coronary plaque formation remain poorly understood. 1 Numerous clinical characteristics and associated laboratory findings (ie, elevated LDL-C levels) have been firmly linked with an increased likelihood of developing atherosclerosis. Some of these variables are modifiable, such as obesity, smoking, hypercholesterolemia, hypertension, and lack of exercise, while other demographic factors such as age, sex, and family history cannot be changed. 2,3 Risk assessment at the individual patient level, however, should not relate to simply accounting for the number of risk factors but rather should focus upon how to delineate the complex interplay among many established clinical and laboratory risk factors. With numerous recent advances, novel biomarkers have been identified from plasma samples of patients with possible or suspected CAD. One such biomarker that looks to be promising is the inflammatory protein—soluble urokinase-type plasminogen activator receptor (suPAR). In the current issue of the Journal of the American Heart Association, Eapen et al 4 present the findings of a study that assessed the association of plasma suPAR with the presence and severity of CAD as well as the role of suPAR as a predictive marker for death and myocardial infarction (MI) (over a mean of 2 years) in 3367 patients undergoing cardiac catheterization. In this study, suPAR levels were associated with both the presence and severity of CAD, and with an increased risk of subsequent death or myocardial infarction (MI) (hazard ratio [HR]: 1.9), cardiac death (HR: 2.62), and MI (HR: 3.20). The addition of suPAR levels to a prediction model that incorporated traditional risk factors modestly improved the discriminatory capabilities of the model (the C statistic changed from 0.72 to 0.74). Urokinase-type plasminogen activator (uPA) and its cell surface-receptor (uPAR) regulate cellular functions linked to adhesion and migration and are involved in the tissue remodeling processes. 5 The soluble form (suPAR) is present in the serum and other bodily fluids, and the soluble receptor accounts for 10% to 20% of the total receptor in vascular endothelial and smooth muscle cells. Numerous observational studies have shown systemic levels of suPAR to be associated with an increased risk of cancer, various infectious and inflammatory diseases, rheumatoid arthritis, and hepatic fibrosis. 6 Furthermore, elevated levels of suPAR have been shown to have prognostic value for patients with neoplasms, systemic inflammatory diseases, and those with various infectious diseases. 6