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Licensed Unlicensed Requires Authentication Published by De Gruyter November 6, 2020

Associations of endothelial biomarkers, nitric oxide metabolites and endothelin, with blood pressure and coronary lesions depend on cardiovascular risk and sex to mark endothelial dysfunction on the SCORE scale

Nadezhda G. Gumanova, Alexander U. Gorshkov, Marina V. Klimushina and Alexander Y. Kots



Endothelial dysfunction contributes to the onset and progression of cardiovascular diseases. However, direct associations of vasoactive mediators with cardiovascular risk are poorly understood.


We have determined associations of circulating levels of stable metabolites of nitric oxide, nitrate and nitrite (NOx), endothelin-1, and the endothelin-1/NOx ratio with blood pressure in 177 asymptomatic subjects without signs of coronary atherosclerosis; associations with blood pressure and with presence of coronary lesions were also evaluated in 457 patients suspected to have coronary heart disease with or without coronary lesions confirmed by coronary angiography. All participants were on a low nitrate diet 24 h prior to blood sampling.


In men, NOx levels were inversely correlated with blood pressure similar to women with low (0–4%) European Systematic Coronary Risk Estimation (SCORE). However, the correlation was not significant in women with high SCORE (5–8%). High systolic blood pressure over 140 mm Hg was negatively associated with NOx levels in asymptomatic men (p=0.05) but not in women. This association is disrupted in male and female patients with coronary atherosclerosis. In male patients, NOx (p=0.05), endothelin (p=0.01), and the endothelin/NOx ratio (p=0.04) were associated with presence of coronary lesions.


Thus, elevated cardiovascular risk according to SCORE over 4% in asymptomatic women, but not in men, is associated with a shift in markers of endothelial dysfunction. Presence of coronary lesions in patients is associated with significant changes in circulating levels of markers of endothelial dysfunction in men but not in women.

Corresponding author: Nadezhda G. Gumanova, National Medical Research Center for Preventive Medicine, Ministry of Healthcare of Russian Federation, 10 Petroverigsky per., building 3, Moscow 101990, Russia, Phone/Fax: +7(499)5516853, E-mail:

Funding source: Russian Foundation for Basic Research

Award Identifier / Grant number: No 17-04-00157

  1. Research funding: The study was supported by the Russian Foundation for Basic Research grant No 17-04-00157.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: The authors declare no conflict of interests.

  4. Informed consent: All participants gave their written informed consent to participate in the study and to grant access to their personal data.

  5. Ethical approval: The study complied with all the relevant national regulations and institutional policies. Study protocols have been approved by the Ethics Committee of NRCPM according to the guidelines of the Helsinki Declaration and WHO.


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Received: 2020-04-21
Accepted: 2020-09-10
Published Online: 2020-11-06

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