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.