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 ( Prx 4), a hydrogen peroxide–degrading peroxidase, with incident CVD and all‐cause mortality. We subsequently examined the incremental value of Prx 4 for the risk prediction of CVD compared with the F ramingham risk score ( FRS ). Methods and Results We performed C ox regression analyses in 8141 participants without history of CVD (aged 28 to 75 years; women 52.6%) from the P revention of R enal and V ascular E nd‐stage D isease ( PREVEND ) study in G roningen, The N etherlands. Serum Prx 4 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 Prx 4 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 F ramingham 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 Prx 4 levels. After the addition of Prx 4 to the FRS , the net reclassification improvement was 2.7% ( P =0.01) using 10‐year risk categories of CVD . Conclusions Elevated serum Prx 4 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 Prx 4 to the FRS marginally improved risk prediction of future CVD .