Cardiovascular risk prediction in the general population with use of suPAR, CRP, and Framingham Risk Score

Int J Cardiol. 2013 Sep 10;167(6):2904-11. doi: 10.1016/j.ijcard.2012.07.018. Epub 2012 Aug 19.


Background: The inflammatory biomarkers soluble urokinase plasminogen activator receptor (suPAR) and C-reactive protein (CRP) independently predict cardiovascular disease (CVD). The prognostic implications of suPAR and CRP combined with Framingham Risk Score (FRS) have not been determined.

Methods: From 1993 to 1994, baseline levels of suPAR and CRP were obtained from 2315 generally healthy Danish individuals (mean [SD] age: 53.9 [10.6] years) who were followed for the composite outcome of ischemic heart disease, stroke and CVD mortality.

Results: During a median follow-up of 12.7 years, 302 events were recorded. After adjusting for FRS, women with suPAR levels in the highest tertile had a 1.74-fold (95% confidence interval [CI]: 1.08-2.81, p=0.027) and men a 2.09-fold (95% CI: 1.37-3.18, p<0.001) increase in risk compared to the lowest tertile. Including suPAR and CRP together resulted in stronger risk prediction with a 3.30-fold (95% CI: 1.36-7.99, p<0.01) increase for women and a 3.53-fold (1.78-7.02, p<0.001) increase for men when both biomarkers were in the highest compared to the lowest tertile. The combined extreme tertiles of suPAR and CRP reallocated individuals predicted to an intermediate 10-year risk of CVD of 10-20% based on FRS, to low (<10%) or high (>20%) risk categories, respectively. This was reflected in a significant improvement of C statistics for men (p=0.034) and borderline significant for women (p=0.054), while the integrated discrimination improvement was highly significant (P≤0.001) for both genders.

Conclusions: suPAR provides prognostic information of CVD risk beyond FRS and improves risk prediction substantially when combined with CRP in this setting.

Keywords: Biomarkers; C-reactive protein; Cardiovascular risk; Framingham Risk Score; Soluble urokinase plasminogen activator receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • C-Reactive Protein / metabolism*
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / diagnosis*
  • Cardiovascular Diseases / epidemiology
  • Denmark / epidemiology
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Population Surveillance / methods
  • Predictive Value of Tests
  • Receptors, Urokinase Plasminogen Activator / blood*
  • Risk Assessment / methods
  • Risk Factors


  • Biomarkers
  • PLAUR protein, human
  • Receptors, Urokinase Plasminogen Activator
  • C-Reactive Protein