Serum nitrite and nitrate levels, NOx, can predict cardiovascular mortality in the elderly in a 3‐year follow‐up study

Abstract

Nitric oxide (NO) is an important functional regulator that contributes to progression of various cardiovascular diseases. We studied associations between nitric oxide metabolites, nitrite and nitrate (NOx), and cardiovascular mortality in a prospective 3-year follow-up cohort study in 1,869 elderly patients aged over 55 years. The Cox proportional hazard regression model was adjusted for multiple factors including sex, age, risk corresponding to preexisting cardiovascular conditions, and serum inflammatory markers (C-reactive protein, interleukin-6, fibrinogen, and leucocytes count). During the follow-up period, there were a total of 348 deaths including 216 deaths unrelated to cardiovascular events and 132 cardiovascular deaths. Cox regression adjusted for factors related to cardiovascular disease risks and inflammatory markers showed a significant association between high levels of serum nitric oxide metabolites, NOx, and increased cardiovascular mortality (hazard ratio 2.21; 95% confidence interval 1.13-4.31) but there was no association with non-cardiovascular mortality. Analysis of adjusted hazard ratios demonstrates that association of serum nitric oxide metabolites with cardiovascular mortality was independent of levels of inflammatory markers. Thus, elevated concentrations of serum nitric oxide metabolites are a predictor of cardiovascular mortality and may be used as an integral marker of cardiovascular death. © 2016 BioFactors, 43(1):82-89, 2017.

Elevated levels of serum nitrite and nitrate, NOx, are associated with increased total and cardiovascular mortality in an 8‐year follow‐up study

“…Our previous work demonstrated that high concentrations of serum NOx can be considered an independent risk factor associated with increased cardiovascular mortality during 3‐year follow‐up. Some other factors were associated with cardiovascular mortality including age, sex, HDL cholesterol, C‐reactive protein, interleukin‐6, fibrinogen and history of previous cardiovascular events . It should be noted that a number of factors were not associated with mortality in the present study in agreement with our previous results .…”

“…Mean NOx concentrations were 58.0 ± 30.4 µmol/L. NOx concentrations did not differ between men and women and between subjects of various age groups …”

“…Levels of various biochemical parameters were compared between the groups similar to our preceding studies and parameters that demonstrated significant differences are listed in Table with particular emphasis on cholesterol metabolism, inflammation and blood coagulation considering results of other authors on identification of various risk factors associated with mortality in the subjects over 55 years of age …”

“…Patients were recruited within the framework of the prospective population cohort survey Stress Aging and Health in Russia (SAHR). Protocol of the study has been described in detail in our preceding publications . The study launched in 2006 as the core of the project Biodemography of Disease and Death in Moscow, 2008.…”

“…In our previous publications, we have demonstrated that high concentrations of serum NOx are independently associated with an increase in cardiovascular mortality in a 3‐year follow‐up study . Moreover, elevated concentrations of NOx can be linked to prevalence of certain non‐infectious diseases including stroke .…”