SOLUBLE ADHESION MOLECULE P-SELECTIN AND ENDOTHELIAL DYSFUNCTION IN ESSENTIAL-HYPERTENSION - IMPLICATIONS FOR ATHEROGENESIS - A PRELIMINARY-REPORT

Objective: Patients with essential hypertension are at high risk of at herosclerotic vascular disease. To investigate this further, we measur ed levels of the soluble adhesion molecule P-selectin, which is associ ated with platelet activity/function and atherosclerosis, von Willebra nd factor, which is a marker of endothelial dysfunction, and plasma fi brinogen. Patients and methods: We studied 104 consecutive patients (4 7 males, 57 females; mean +/- SD age 54.8 +/- 14.1 years) with essenti al 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). Results: Compare d with normotensives, the hypertensives showed significant increases i n 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 less than or equal to 0.001) and fibrinogen (3.3 versus 2.9 g/l; unpaired t-test P less than or equal to 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 n ot between P-selectin and von Willebrand factor. There were no differe nces in these factors between patients with (n = 53) and without (n = 51) antihypertensive therapy or between those with good blood pressure control (systolic/diastolic less than or equal to 160/90 mmHg; n = 17 ) and these 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). Conclusions: This study suggests that hypertensives have high p lasma fibrinogen levels, platelet dysfunction (which could contribute to atherogenesis, as indicated by raised soluble P-selectin levels) an d 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.