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

TY - JOUR

T1 - Plasma Nitrate and Incidence of Cardiovascular Disease and All-Cause Mortality in the Community: The Framingham Offspring Study

AU - Maas, Renke

AU - Xanthakis, Vanessa

AU - Göen, Thomas

AU - Müller, Johannes

AU - Schwedhelm, Edzard

AU - Böger, Rainer H

AU - Vasan, Ramachandran S.

N1 - © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

PY - 2017/11/18

Y1 - 2017/11/18

N2 - BACKGROUND: Nitrate is a dietary component as well as an endogenously formed metabolite and source of the signaling molecule nitric oxide. Harmful as well as beneficial effects of nitrate have been advocated. Data regarding the prognostic relevance of plasma nitrate are limited. The aim of this study was to evaluate the prospective association of plasma nitrate with cardiovascular disease (CVD) and all-cause mortality.METHODS AND RESULTS: We assayed plasma nitrate in 2855 Framingham Offspring Study participants (mean age 59 years, 54% women) by gas chromatography-mass spectrometry and evaluated its association with all-cause mortality and incident CVD. On follow-up (median 17.3 years), 775 participants died and 522 developed new-onset CVD (of 2546 participants free of CVD at baseline). In multivariable models adjusting for standard risk factors, plasma nitrate was associated with an increased risk of death in participants (hazard ratio per unit increase in log-nitrate 1.21; 95% confidence interval, 1.04-1.40 [P=0.015]). The strength of the association was attenuated by additional adjustment for estimated glomerular filtration rate (hazard ratio, 1.16; 95% confidence interval, 1.00-1.35 [P=0.057]). In contrast, no evidence was found for an association of plasma nitrate with incident CVD (multivariable-adjusted hazard ratio per unit increase log-nitrate 1.08; 95% confidence interval, 0.89-1.31 [P=0.42]).CONCLUSIONS: In our prospective community-based investigation, a higher plasma nitrate concentration was associated with all-cause mortality but not with incident CVD. The association of nitrate with mortality may at least in part be attributable to its association with renal function.

AB - BACKGROUND: Nitrate is a dietary component as well as an endogenously formed metabolite and source of the signaling molecule nitric oxide. Harmful as well as beneficial effects of nitrate have been advocated. Data regarding the prognostic relevance of plasma nitrate are limited. The aim of this study was to evaluate the prospective association of plasma nitrate with cardiovascular disease (CVD) and all-cause mortality.METHODS AND RESULTS: We assayed plasma nitrate in 2855 Framingham Offspring Study participants (mean age 59 years, 54% women) by gas chromatography-mass spectrometry and evaluated its association with all-cause mortality and incident CVD. On follow-up (median 17.3 years), 775 participants died and 522 developed new-onset CVD (of 2546 participants free of CVD at baseline). In multivariable models adjusting for standard risk factors, plasma nitrate was associated with an increased risk of death in participants (hazard ratio per unit increase in log-nitrate 1.21; 95% confidence interval, 1.04-1.40 [P=0.015]). The strength of the association was attenuated by additional adjustment for estimated glomerular filtration rate (hazard ratio, 1.16; 95% confidence interval, 1.00-1.35 [P=0.057]). In contrast, no evidence was found for an association of plasma nitrate with incident CVD (multivariable-adjusted hazard ratio per unit increase log-nitrate 1.08; 95% confidence interval, 0.89-1.31 [P=0.42]).CONCLUSIONS: In our prospective community-based investigation, a higher plasma nitrate concentration was associated with all-cause mortality but not with incident CVD. The association of nitrate with mortality may at least in part be attributable to its association with renal function.

KW - Journal Article

U2 - 10.1161/JAHA.117.006224

DO - 10.1161/JAHA.117.006224

M3 - SCORING: Journal article

C2 - 29151027

VL - 6

JO - J AM HEART ASSOC

JF - J AM HEART ASSOC

SN - 2047-9980

IS - 11

ER -