SERUM NITRITE AND NITRATE LEVELS, NOX, IN CARDIOVASCULAR MORTALITY STUDY: 3 AND 7 YEAR FOLLOW UP

N. Gumanova, A. Deev and S. Shalnova

Department of Biochemistry, National Research Center for Preventive Medicine, Moscow, Russia

Abstract

Aim: Nitric oxide (NO) is an important functional regulator that contributes to progression of various cardiovascular diseases. We studied associations between circulating nitric oxide metabolites, nitriteand nitrate (NOx), and cardiovascular mortality.

Methods: A prospective cohort study in 1,876 elderly Muscovite subjects aged 55 years and older. The Cox proportional hazard regression model was adjusted for multiple factors including sex, age, preexisting cardiovascular conditions, and serum inflammatory markers. The log-rank test in Kaplan-Meier survival analysis was also used. Concentrations of nitrate and nitrite (NOx) were measured in deproteinized serum using Griess reaction after reduction with vanadium (III) chloride. Other biochemical parameters were measured by ELISA kits or automatic analyzers.

Results: Cox regression adjusted for factors related to cardiovascular disease risks and inflammatory markers showed a significant association between high levels of NOx =75 μM and increased cardiovascular mortality (HR 2.21; 95% CI 1.13–4.31; P=0.02) and no association with all-cause mortality in a 3-year follow-up. Analysis of adjusted HRs demonstrates that association of NOx with cardiovascular mortality was independent of levels of inflammatory markers: CRP, IL-6, fibrinogen, leucocytes. Results of 7-year follow-up study demonstrated that high serum levels of NOx, =70 μM are still associated with cardiovascular mortality although HR was reduced compared to 3-year follow up (HR 1.6; 95% CI 1.06–2.26, P=0.01). Moreover, NOx becomes associated with all-cause mortality (HR 1.5; 95% CI 1.16–2.06, P=0.003). Kaplan-Meier survival analysis indicates that cardiovascular mortality and total mortality was increased in men with high serum NOx =70 μM versus mean with low NOx levels <40 μM (Log-rank p=0.01 Wilcoxon - 0.003). These associations were not observed in women.

Conclusions: Elevated concentrations of serum NOx =70 μM are a long-term predictor of cardiovascular and all-cause mortality specifically in men. Elevated concentrations of serum NOx are also a short term predictor of cardiovascular mortality for men and women and may be used as a marker of cardiovascular death. The reported study was funded by RFBR according to the research project ? 17-04-00157\17.

Keywords: Nitate, nitrite, markers, cardiovascular, mortality.