Soluble adhesion molecule P-selectin and endothelial dysfunction in essential hypertension

Abstract

Patients with essential hypertension are at high risk of atherosclerotic vascular disease. To investigate this further, we measured levels of the soluble adhesion molecule P-selectin, which is associated with platelet activity/function and atherosclerosis, von Willebrand factor, which is a marker of endothelial dysfunction, and plasma fibrinogen. We studied 104 consecutive patients (47 males, 57 females; mean +/- SD age 54.8 +/- 14.1 years) with essential hypertension compared with 47 normotensive healthy controls (55.0 +/- 19.2 years). Levels of soluble adhesion molecule P-selectin and von Willebrand factor were measured by enzyme-linked immunosorbent assay, and plasma fibrinogen by a clotting method (CLAUSS). Compared with normotensives, the hypertensives showed significant increases in soluble P-selectin (300 versus 228 ng/ml; median difference 55 ng/ml, Mann-Whitney test P = 0.03), von Willebrand factor (114 versus 96 IU/I; unpaired t-test P < or = 0.001) and fibrinogen (3.3 versus 2.9 g/l; unpaired t-test P < or = 0.001). There were significant correlations between fibrinogen and P-selectin (r = 0.16; P = 0.02) and von Willebrand factor (r = 0.39; P<0.001), but not between P-selectin and von Willebrand factor. There were no differences in these factors between patients with (n = 53) and without (n = 51) antihypertensive therapy or between those with good blood pressure control (systolic/diastolic < or = 160/90 mmHg; n = 17) and those with poor control. A stepwise multiple regression analysis showed that diastolic blood pressure was a significant predictor for soluble P-selectin levels; diastolic blood pressure and von Willebrand factor levels were significant predictors for fibrinogen levels (P<0.05). This study suggests that hypertensives have high plasma fibrinogen levels, platelet dysfunction (which could contribute to atherogenesis, as indicated by raised soluble P-selectin levels) and endothelial dysfunction (as indicated by high von Willebrand factor levels), which are related to diastolic blood pressure. These factors may act synergistically to increase atherogenesis and may explain the high risk of atherosclerotic vascular disease in hypertensives.