Cardiovascular risk prediction in the general population with use of suPAR, CRP, and Framingham Risk Score.
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.
Department of Cardiology, Copenhagen University Hospital Gentofte, Denmark. stiglyngbaek@gmail.com
Stig
S
Lyngbæk
Jacob L
JL
Marott
Thomas
T
Sehestedt
Tine W
TW
Hansen
Michael H
MH
Olsen
Ove
O
Andersen
Allan
A
Linneberg
Steen B
SB
Haugaard
Jesper
J
Eugen-Olsen
Peter R
PR
Hansen
Jørgen
J
Jeppesen
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D003718:Denmark / Q000453:epidemiology; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods; D011237:Predictive Value of Tests; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood*; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors
D015415:Biomarkers; C524898:PLAUR protein, human; D055293:Receptors, Urokinase Plasminogen Activator; D002097:C-Reactive Protein