title: Peroxiredoxin 4, a novel circulating biomarker for oxidative stress and the risk of incident cardiovascular disease and all-cause mortality.
abstract: BACKGROUND
  Oxidative stress has been suggested to play a key role in the development of cardiovascular disease (CVD). The aim of our study was to investigate the associations of serum peroxiredoxin 4 (Prx4), a hydrogen peroxide-degrading peroxidase, with incident CVD and all-cause mortality. We subsequently examined the incremental value of Prx4 for the risk prediction of CVD compared with the Framingham risk score (FRS).
  
  
  RESULTS
  We performed Cox regression analyses in 8141 participants without history of CVD (aged 28 to 75 years; women 52.6%) from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study in Groningen, The Netherlands. Serum Prx4 was measured by an immunoluminometric assay in baseline samples. Main outcomes were: (1) incident CVD events or CVD mortality and (2) all-cause mortality during a median follow-up of 10.5 years. In total, 708 participants (7.8%) developed CVD events or CVD mortality, and 517 participants (6.3%) died. Baseline serum Prx4 levels were significantly higher in participants with incident CVD events or CVD mortality and in those who died than in participants who remained free of outcomes (both P<0.001). In multivariable models with adjustment for Framingham risk factors, hazard ratios were 1.16 (95% CI 1.06 to 1.27, P<0.001) for incident CVD events or CVD mortality and 1.17 (95% CI 1.06 to 1.29, P=0.003) for all-cause mortality per doubling of Prx4 levels. After the addition of Prx4 to the FRS, the net reclassification improvement was 2.7% (P=0.01) using 10-year risk categories of CVD.
  
  
  CONCLUSIONS
  Elevated serum Prx4 levels are associated with a significantly higher risk of incident CVD events or CVD mortality and all-cause mortality after adjustment for clinical risk factors. The addition of Prx4 to the FRS marginally improved risk prediction of future CVD.
authors: Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. a.abbasi@umcg.nl
authors: Ali
authors: A
authors: Abbasi
authors: Eva
authors: E
authors: Corpeleijn
authors: Douwe
authors: D
authors: Postmus
authors: Ron T
authors: RT
authors: Gansevoort
authors: Paul E
authors: PE
authors: de Jong
authors: Rijk O B
authors: RO
authors: Gans
authors: Joachim
authors: J
authors: Struck
authors: Janin
authors: J
authors: Schulte
authors: Hans L
authors: HL
authors: Hillege
authors: Pim
authors: P
authors: van der Harst
authors: Linda M
authors: LM
authors: Peelen
authors: Joline W J
authors: JW
authors: Beulens
authors: Ronald P
authors: RP
authors: Stolk
authors: Gerjan
authors: G
authors: Navis
authors: Stephan J L
authors: SJ
authors: Bakker
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D018384:Oxidative Stress / Q000502:physiology*; D054464:Peroxiredoxins / Q000097:blood*; D012044:Regression Analysis; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D054464:Peroxiredoxins
keywords: cardiovascular disease; epidemiology; mortality; oxidative stress; peroxiredoxin 4