Soluble urokinase plasminogen activator receptor in plasma is associated with incidence of CVD. Results from the Malmö 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 Malmö 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-PLA(2) (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.