Serum nitric oxide metabolites and hard clinical endpoints: a population-based prospective study

Abstract

Objective. Limited data are available regarding prognostic value of nitric oxide metabolites (NOx) for clinical hard end points. In this study, we defined optimum cut-off values of serum NOx for predicting all-cause and cardiovascular disease (CVD) mortality events and prospectively investigated their hazards in the presence of traditional risk factors. Design. Serum NOx concentrations were measured at baseline (2006–2008) and 3520 adult men and women were followed during 7.7 years for all-cause and cardiovascular disease (CVD) mortality. To determine the optimal cut-off points of serum NOx, the receiver operator characteristic (ROC) curve analysis was used. Multivariate Cox proportional hazard models were used to estimate the hazard ratios (HRs) with 95% confidence intervals (95% CIs) of all-cause and CVD mortality below and above the defined optimal cut-off points of serum NOx. Results. Mean age of participants was 44.5 ± 16.0 years at baseline and 40.2% were male. Median (inter-quartile range) of serum NOx levels was 25.0 µmol/L (19.0–37.0), at baseline. The optimal cut-off points of serum NOx levels for predicting CVD and all-cause mortality were 30.5 and 32.5 µmol/L, respectively. In the presence of age, sex, body mass index, smoking, type 2 diabetes, hypertension, and history of CVD, a significant increased risk of CVD mortality (HR = 1.98, 95% CI = 1.10–3.58) and all-cause mortality (HR = 1.52, 95% CI = 1.05–2.21) was observed for serum NOx values higher than their cut-offs. Conclusion. Serum NOx level may be predictor of CVD mortality and death, in general populations.