A cross-sectional, diurnal, and follow-up study of platelet activation and endothelial dysfunction in malignant phase hypertension

Abstract

To investigate the hypothesis that abnormalities of thrombogenesis and endothelial damage/dysfunction are greater in malignant hypertension (MHT) compared with uncomplicated nonmalignant essential hypertension (EHT) > 160/90 mm Hg), we measured markers of endothelial function (von Willebrand factor) platelet activation (soluble P-selectin) and fibrinogen in 18 consecutive patients with MHT, 50 patients with untreated EHT, and 34 healthy control subjects. We also investigated whether there was any diurnal variation in the measured indices, as well as the effects of good blood pressure (BP) control after 6-month follow-up. Mean plasma fibrinogen and von Willebrand factor levels were both highest in the MHT group, intermediate in the nonmalignant hypertension group and lowest in the normotensive control subjects ( P < .001). Similarly, mean soluble P-selectin levels were higher in both hypertensive groups compared to normotensive control subjects ( P = .033). There was no significant diurnal variation in plasma fibrinogen, soluble P-selectin, and von Willebrand factor levels over the 24-h study period among the MHT patients. At 6-month follow-up and a reduction in mean BP, there was no significant change in mean plasma fibrinogen levels ( P = .25), but both soluble P-selectin ( P < .001) and von Willebrand factor ( P = .0025) were significantly reduced. In conclusion, malignant hypertension is associated with abnormal endothelial damage (elevated von Willebrand factor), platelet activation (soluble P-selectin), and fibrinogen levels, which may be related to the pathogenesis of this condition, as well as the development of complications. These abnormalities do not undergo any significant diurnal variation and may be beneficially altered by BP reduction.