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).

METHODS AND 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: Ali Abbasi, Eva Corpeleijn, Douwe Postmus, Ron T Gansevoort, Paul E de Jong, Rijk O B Gans, Joachim Struck, Janin Schulte, Hans L Hillege, Pim van der Harst, Linda M Peelen, Joline W J Beulens, Ronald P Stolk, Gerjan Navis, Stephan J L Bakker
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 1 Issue 5 Pg. e002956 (Oct 2012) ISSN: 2047-9980 [Electronic] England
• PMID: 23316297 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Peroxiredoxins

Topics

• Adult
• Aged
• Biomarkers (blood)
• Cardiovascular Diseases (blood, diagnosis, mortality)
• Female
• Humans
• Male
• Middle Aged
• Netherlands
• Oxidative Stress (physiology)
• Peroxiredoxins (blood)
• Regression Analysis
• Risk Factors