title: Soluble urokinase plasminogen activator receptor is associated with subclinical organ damage and cardiovascular events.
abstract: OBJECTIVE
  The soluble urokinase plasminogen activator receptor (suPAR) is a plasma marker of low grade inflammation and has been associated with cardiovascular risk. We wanted to investigate whether suPAR was associated with markers of subclinical organ damage.
  
  
  METHODS
  In a population sample of 2038 individuals, aged 41, 51, 61 and 71 years, without diabetes, prior stroke or myocardial infarction, not receiving any cardiovascular, anti-diabetic or lipid-lowering medications, we measured urine albumin/creatinine ratio (UACR), carotid atherosclerotic plaques and carotid/femoral pulse wave-velocity (PWV) together with traditional cardiovascular risk factors and high sensitivity C-reactive protein (hsCRP).
  
  
  RESULTS
  suPAR was significantly associated with the presence of plaques (P = 0.003) and UACR (P < 0.001), but not PWV (P = 0.17) when adjusting for age, gender, systolic blood pressure, cholesterol, plasma glucose, waist/hip ratio, smoking and hsCRP. However, suPAR explained only a small part of the variation in the markers of subclinical organ damage (R(2) 0.02-0.04). During a median follow-up of 12.7 years (5th-95th percentile 5.1-13.4 years) a total of 174 composite endpoints (CEP) of cardiovascular death, non-fatal myocardial infarction and stroke occurred. suPAR was associated with CEP independent of plaques, PWV, UACR, and hsCRP as well as age, gender, systolic blood pressure, cholesterol, plasma glucose, waist/hip ratio and smoking with a standardized hazard ratio of 1.16 (95% confidence interval 1.04-1.28, P = 0.006).
  
  
  CONCLUSIONS
  suPAR was associated with subclinical organ damage, but predicted cardiovascular events independent of subclinical organ damage, traditional risk factors and hsCRP. Further studies must investigate whether suPAR plays an independent role in the pathogenesis of cardiovascular disease.
authors.affiliation: Cardiovascular Research Unit, Department of Internal Medicine, Copenhagen University Hospital, Nordre Ringvej 57, 2600 Glostrup, Denmark. ts@heart.dk
authors.forename: T
authors.initials: T
authors.lastname: Sehestedt
authors.forename: S
authors.initials: S
authors.lastname: Lyngbæk
authors.forename: J
authors.initials: J
authors.lastname: Eugen-Olsen
authors.forename: J
authors.initials: J
authors.lastname: Jeppesen
authors.forename: O
authors.initials: O
authors.lastname: Andersen
authors.forename: T W
authors.initials: TW
authors.lastname: Hansen
authors.forename: A
authors.initials: A
authors.lastname: Linneberg
authors.forename: T
authors.initials: T
authors.lastname: Jørgensen
authors.forename: S B
authors.initials: SB
authors.lastname: Haugaard
authors.forename: M H
authors.initials: MH
authors.lastname: Olsen
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000097:blood / Q000150:complications* / Q000401:mortality / Q000503:physiopathology; D000704:Analysis of Variance; D058070:Asymptomatic Diseases; D050197:Atherosclerosis / Q000097:blood / Q000150:complications* / Q000000981:diagnostic imaging / Q000401:mortality / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D017536:Carotid Artery, Common / Q000503:physiopathology; D016009:Chi-Square Distribution; D003187:Compliance; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005263:Femoral Artery / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications* / Q000401:mortality / Q000503:physiopathology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000150:complications* / Q000000981:diagnostic imaging / Q000401:mortality / Q000503:physiopathology; D016016:Proportional Hazards Models; D011673:Pulsatile Flow; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood*; D018570:Risk Assessment; D012307:Risk Factors; D014463:Ultrasonography
chemical_list: D015415:Biomarkers; C524898:PLAUR protein, human; D055293:Receptors, Urokinase Plasminogen Activator