Abstract 14141: Plasma Nitrate and Incidence of Cardiovascular Disease and All-cause Mortality in the Community: The Framingham Offspring Study

Abstract

Introduction. Plasma nitrate largely originates from human diet and endogenous nitric oxide signaling. Beneficial, as well as detrimental, effects of nitrate have been proposed. Long term prospective data regarding the prognostic significance of plasma nitrate are very limited. We evaluated the association of plasma nitrate with incident CVD and all-cause mortality prospectively in a large cohort. Methods. We determined plasma nitrate concentrations using gas-chromatography mass-spectrometry in participants of the community-based Framingham Study Offspring Cohort. Results. Natural-logarithmically transformed plasma nitrate concentrations were positively related to smoking, diabetes, alcohol consumption and antihypertensive medication use and inversely related to estimated glomerular filtration rate (eGFR) (p<0.05 for all). Of 2513 participants (56% women, mean age 58.1) who were free of CVD at baseline, 372 developed incident CVD during follow-up (median 10.3 years). We did not observe any significant association of plasma nitrate and incident CVD (hazard ratio [HR] per unit increase log-nitrate 1.12, 95% CI 0.90-1.41, p=0.31). On follow-up (median 11.3 years) of 2815 participants (54% women, mean age 58.9 years; 302 with prevalent CVD), 464 participants died. We identified a significant statistical interaction of plasma nitrate and eGFR with respect to all-cause mortality (p=0.02). Therefore, separate Cox regression models, adjusting for prevalent CVD and standard CVD risk factors, were estimated for individuals with an eGFR at or above and below the median (83.8 ml/min). In individuals with an eGFR at or above the median plasma nitrate was not associated with total mortality (HR per unit increase log-nitrate 0.97, 95% CI: 0.69-1.37, p=0.88) whereas in participants with an eGFR below the median higher plasma nitrate was associated with a significantly increased risk of death (HR per unit increase in log-nitrate 1.38, 95% CI: 1.09-1.74, p=0.007). Conclusions. In our large community-based sample, higher plasma nitrate concentrations were associated with all-cause mortality in the subset of participants with eGFR below the median, possibly because higher plasma nitrate levels may be a marker of lower renal function in this group.