Association of Urinary Nitrate With Lower Prevalence of Hypertension and Stroke and With Reduced Risk of Cardiovascular Mortality
Authors: Angelico Mendy
Journal: Circulation (2018)

◼ nitrate ◼ nitric oxide ◼ stroke U rinary nitrate derives from endogenous and dietary sources.Endogenous nitrate results from the oxidization of nitric oxide (NO) produced by endothelial NO synthase and can be suggestive of NO synthase-NO bioavailability.Dietary nitrate, found mostly in green leafy vegetables or beetroot, partly enters the enterosalivary circulation to be converted to nitrite by oral bacteria.Nitrite from endogenous and dietary nitrate are reduced to NO by reactions with hemoglobin, myoglobin, and molybdopterin enzymes. 1 Because NO is a potent regulator of vascular homoeostasis and integrity, this study examined in a large sample representative of the US population the association of urinary nitrate with cardiovascular disease (CVD) prevalence and mortality as primary outcomes and with cancer and all-cause mortality as secondary outcomes.CVD is the leading cause of death worldwide and in the United States, where it accounts for nearly 1 in every 4 deaths.Data on 17 618 adult participants in the NHANES (National Health and Nutrition Examination Surveys), conducted between 2005 and 2014 in the United States, were analyzed.The NHANES protocols were approved by the Institutional Review Boards of the National Center for Health Statistics and the Centers for Disease Control, and informed consent was obtained from each participant.Nitrate was analyzed in a spot urine sample using ion chromatography with tandem mass spectrometry.Hypertension was defined by self-reported physician diagnosis, use of antihypertensive medication, mean systolic blood pressure (of 4 measurements on 2 separate occasions) ≥140 mm Hg or mean diastolic blood pressure ≥90 mm Hg.Myocardial infarction and stroke were defined by self-reported physician diagnosis.A subset of 11 893 participants in the NHANES between 2005 and 2010 was prospectively followed for mortality through 2011 (median 4.34 years) using National Death Index records and death certificates.Cardiovascular mortality was defined using the tenth revision of the International Classification of Diseases.Logistic regression and Cox proportional hazards regression analysis were used to calculate the odds ratio and hazard ratio for the association of log-transformed urinary nitrate with the outcomes.The models were adjusted for age, sex, race/ ethnicity, poverty income ratio, body mass index, cigarette smoking, hypertension, hypercholesterolemia, diabetes mellitus, physical activity, and urinary creatinine.The NHANES sampling weights and complex survey design were applied so that estimates are nationally representative.The median age of participants was 45 years.The prevalence of hypertension was 32.8%, 2.6% for stroke, and 3.2% for myocardial infarction.Among participants followed for mortality, 628 died, including 120 of CVD.The geometric mean (standard error) of urinary nitrate was 726.14 (11.42) uM/L.Urinary nitrate was significantly lower in individuals with hypercholesterolemia, diabetes mellitus, hypertension, myocardial infarction, or stroke.In logistic regression analysis,