PROGNOSTIC SIGNIFICANCE OF ENDOTHELIAL DYSFUNCTION MARKERS IN ARTERIAL HYPERTENSION

Aim. Assessment of prognostic significance of endothelial dysfunction markers: stable metabolites of nitric oxide (NOx), von Willebrand factor (vWF), endothelin-1 (E1), homocysteine and tissue plasminogen activator (tPA) in essential hypertension (EAH) patients not taking antihypertension therapy systematically.

Material  and  methods. Totally, 12 EAH patients investigated (45 males, 79 females) (mean age 51,4±6,5 y. o., mean duration of AH 7,9±7,3 y.). Concentration of NOx in plasma was measured by spectrophotometry, and of vWF, homocysteine, E1 and tPA — by immune enzyme assay.

Results. By the increase of SCORE risk level, there was significant increase of concentrations of NOx, E1, homocysteine and vWF in EAH patients (p<0,05), there were no changes in tPA levels (p>0,05). In 8 (8±1,1) years after baseline assessment, 115 patients were assessed second time. Of those 13 (11,3%) had cardiovascular events (CVE) and 5 (4,3%) died. By single factorial regression, the rate of CVE in EAH patients relate to homocystein level (р=0,01), NOx (р=0,001) and vWF (р=0,001). By multifactorial analysis, prognostic statistical significance is found for NOx (relative risk (RR) =3,8, р=0,006) and vWF (RR =3,5, р=0,005). In ROC-analysis there were found threshold levels of NOx (>46,6 mcM/L, AUC =0,863) and vWF (>1,68 mg/dL, AUC =0,738), the increase of which is followed by CVE development
risk for the levels of NOx >46,6 mcM/L 3,8 times (sensitivity 81,9% and specificity 65,8%), vWF >1,68 mg/dL — 3,5 times (sensitivity 74,3% and specificity 62,7%). Combination of the parameters point on the risk increase up to 6,5 times (р=0,00007).

Conclusion. NOx with the threshold of >46,6 mcM/L (RR =3,8) and vWF >1,68 mg/dL (RR =3,5) do show independent prognostic value for 5-year CVE risk assessment in EAH patients that can be applied as an additional method for risk stratification to estimate a group for more aggressive therapy and CVE prevention.

1. Whelton PK, et al. High Blood Pressure Clinical Practice Guideline/ 2017 by the American College of Cardiology Foundation and the American Heart Association, Inc. Hypertension is available at http://hyper.ahajournals.org/Hypertension. 2017; 00:e000-e000

2. Podzolkov VI Arterial hypertension Moscow MIA 2016 p.426 Russian (Подзолков В.И. Артериальная гипертензия Москва МИА 2016 с.426)

3. R. Lee, M. Margaritis, K.M. Channon, C. Antoniades Evaluating oxidative stress in human cardiovascular disease: methodological aspects and considerations/Current Medicinal Chemistry, 2012, 19, 2504-2520

4. Podzolkov VI, Bragin AE, Murashko NA The level of stable metabolites of nitric oxide in patients with essential hypertension with obesity and hyperleptinemia / Cardiology, 2016, No. 7 (56), Р. 14-19 (Подзолков В.И, Брагина А.Е., Мурашко Н.А. Уровень стабильных метаболитов оксида азота у больных эссенциальной гипертензией с ожирением и гиперлептинемией/ Кардиология, 2016, №7(56), С. 14-19)

5. Jie Dong, Yan-Jun Li, Zhi-Kai Yang, et al. / Prognostic value of serum von Willebrand factor, but not soluble ICAM and VCAM, for mortality and cardiovascular events is independent of residual renal function in peritoneal dialysis patients/ Peritoneal Dialysis International 2014, Vol. 34, pp. 706–713

6. Iida M, Nihei M, Yamazaki M et al. Predictive value of von Willebrand factor for adverse clinical outcome in hypertensive patients with mild-to-moderate aortic regurgitation./ J Hum Hypertens.- 2008.- Vol.22.- Р.275-81.

7. Kimihiro Igari, Toshifumi Kudo, Takahiro Toyofuku, et al. /The relationship between endothelial dysfunction and endothelial cell markers in peripheral arterial disease PLoS One. 2016 Nov 18;11(11): e0166840.

8. Dudchak, A.P. Nitric oxide as a marker of risk of formation of arterial hypertension in children Clinical pediatrics 2008.- 4.- P.59-62 Russian (Дудчак, А.П Оксид азота как маркер риска формирования артериальной гипертензии у детей Клиническая педиатрия 2008.- 4.- С.59-62)

9. Gkaliagkousi E, Gavriilaki E, Triantafyllou A, et al. Clinical Significance of Endothelial Dysfunction in Essential Hypertension. Curr Hypertens Rep. 2015 Nov: 17(11):85.

10. Guidelines Committee ESH-ESC. 2013 ESH-ESC guidelines for the management of arterial hypertension. J Hypertension 2013.- Vol.31.- Р.1281-1357.

11. Conroy RM, Pyorala K, Fitzgerald AP, et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. /Eur Heart J.- 2003.- Vol.24.-Р.987-1003.

12. Podzolkov VI Tarzimanova A.I. Mohammadi LN et al. Changes in endothelial function in patients with arterial hypertension with various forms of atrial fibrillation. Clinical medicine. 2014.Т.92 №3 P. 42-46 Russian (Подзолков В.И. Тарзиманова А.И. Мохаммади Л.Н. и др. Изменение функции эндотелия у больных артериальной гипертонией при различных формах фибрилляции предсердий Клиническая медицина. 2014.Т.92 №3 С.42-46)

13. Ghasemi, A. Serum nitric oxide metabolite levels in a general healthy population: relation to sex and age. / Life Sci. -2008.- Vol.29.- Р.326-331

14. Podzolkov V.I. Bragin A.E. Murashko N.A. The state of the endothelial nitroxide-producing function and left ventricular hypertrophy in patients with essential hypertension Cardiovascular therapy and prevention, 2017; 16 (4) P. 11-17 Russian (Подзолков В.И. Брагина А.Е. Мурашко Н.А. Состояние нитроксидпродуцирующей функции эндотелия и гипертрофия левого желудочка у больных гипертонической болезнью Кардиоваскулярная терапия и профилактика, 2017; 16(4) С. 11-17)

15. La Mura V, Reverter JC, Flores-Arroyo A. et al. /Von Willebrand factor levels predict clinical outcome in patients with cirrhosis and portal hypertension. Gut. 2011 Aug; 60(8):1133-8.