Soluble urokinase plasminogen activator receptor in plasma is associated with incidence of CVD. Results from the Malmo Diet and Cancer Study

Background: Soluble urokinase plasminogen activator receptor (suPAR) is a highly sensitive marker that reflects increased inflammation and is positively correlated with pro-inflammatory biomarkers. The aim of this study was to explore the relationship between suPAR, cardiovascular disease (CVD) risk factors and incidence of CVD. Methods: suPAR was assessed in a random sample of participants (N = 569), aged 63-68 years (mean age 65.5), from the Malmo Diet and Cancer Study (MDCS) cardiovascular cohort. Baseline examination was conducted between 1991 and 1994. suPAR in blood was analysed using a commercially available assay (suPARnostic). Cox regression analysis was used to investigate the incidence of CVD (coronary events or ischemic stroke), in relation to sex-specific tertiles of suPAR. Results: Significantly higher plasma levels of suPAR was found in women, smokers, diabetics and older subjects. suPAR was significantly positively correlated with markers of systemic inflammation (i.e., high sensitive C-reactive protein (hsCRP) and white blood cells (WBC), but not to lipoprotein-associated phospholipase A2 (Lp-PLA(2)), a specific vascular inflammatory biomarker. 87 subjects had a CVD event during follow-up (mean 14.1 years). In an age/sex-adjusted model, the hazard ratio (HR) for incident CVD was 2.53 (95% CI: 1.44-4.46) for the top compared to the bottom tertile of suPAR. This association remained significant after further adjustment for smoking, low density lipoprotein (LDL), systolic blood pressure, use of anti-hypertensive medication, diabetes, hsCRP, WBC and Lp-PLA2 (HR: 2.25; 1.07-4.72). Conclusion: Elevated levels of suPAR are, independently of established cardiovascular risk factors, associated with an increased incidence of CVD in elderly subjects. (C) 2011 Elsevier Ireland Ltd. All rights reserved.