Circulating markers of nitric oxide homeostasis and cardiometabolic diseases: insights from population-based studies

Emerging data suggest that impaired nitric oxide (NO) homeostasis has a key role in development of cardiometabolic disorders. The association between circulating levels of NO metabolites, i.e. nitrate and nitrite (NOx), and risk of chronic diseases has not yet been fully clarified. This work aims to address epidemiologic aspects of NO metabolism and discusses different physiologic and pathophysiologic conditions influencing circulating NOx. Further, cross-sectional associations of serum NOx with metabolic disorders are described and along the way, potential short-term and long-term power of serum NOx for predicting cardiometabolic outcomes are reviewed. Results from population-based studies show that circulating NOx is affected by aging, smoking habits, pregnancy, menopause status, thyroid hormones, and various pathologic conditions including type 2 diabetes, insulin resistance, hypertension, and renal dysfunction. Lifestyle factors, especially dietary habits, but also smoking habits and the degree of physical activity influence NO homeostasis and the circulating levels of NOx. Elevated serum NOx, due to increased iNOS activity, is associated with increased incidence of metabolic syndrome, different obesity phenotypes, and cardiovascular events.