Human serum paraoxonase concentration predicts cardiovascular mortality in hemodialysis patients

Aims: Human serum paraoxonase (PON1) is associated with high-density lipoprotein, and inhibits oxidative modification of low-density lipoprotein. Therefore, PON1 is supposed to contribute to the prevention of atherosclerosis. We and other investigators have shown that the enzymatic activities and concentrations of PON1 were decreased in maintenance hemodialysis (HD) patients. However, the effect of PON 1 status on the long-term outcome of HD patients has not been reported. In this study, we examined the association between baseline PON 1 status and cardiovascular mortality in an observation study of an outpatient HD population. Patients and methods: The relation between baseline cardiovascular risk factors and clinical events was investigated, during 6 years of follow-up, in 81 HD patients (50 males and 31 females) whose enzymatic activities, concentrations and genetic polymorphisms of PON1 had been determined in a previous study. Results: During follow-up for 6 years, we recorded 42 deaths, including 24 fatal cardiovascular events. In univariate analyses, baseline PON1 concentration was associated with not only cardiovascular mortality (p < 0.005), but also all-cause mortality (p < 0.001) during the period of follow-up, as were age, preexisting cardiovascular disease (CVD) and hemoglobin concentration. In a multivariate Cox regression analysis, PON1 concentration retained significant associations with cardiovascular mortality (p < 0.05) and all-cause mortality (p < 0.005) even after correction of known risk factors for CVD or mortality in HD patients. Using Kaplan-Meier survival curves, we assessed the association between low and high concentrations of PON 1 divided according to the median value (7.52 U/ml). Significantly increased cardiovascular mortality (log rank 6.125, p = 0.01) and all-cause mortality (log rank 7.113, p < 0.01) were detected in the patients with low PON 1 concentrations. Conclusions: These data suggest that low PON 1 concentration may be an independent predictor of cardiovascular mortality in maintenance HD patients.