title: Von Willebrand factor, soluble P-selectin, and target organ damage in hypertension: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).
abstract: To investigate the relationship between soluble markers of platelet, endothelial and rheological function, and target organ damage and their response to intensified management in a population of middle-age hypertensive patients at high risk of cardiovascular complications, we studied 382 consecutive patients (308 men; mean age, 63 years, SD 8) along with 60 normotensive controls free of cardiovascular disease. Patients were divided into those with target organ damage (TOD; n=107) and those free of end-organ damage. Plasma levels of soluble P-selectin (sP-sel), a marker of platelet activation, and von Willebrand factor (vWF), an index of endothelial damage/dysfunction (both enzyme-linked immunosorbent assay), and the rheological indices fibrinogen, plasma viscosity, hematocrit, platelet, and white cell count were measured. In 53 patients, variables were further measured after 6 months of intensified cardiovascular risk management. Patients with TOD had significantly higher vWF, 137 (SD 33) versus 125 (SD 33) IU/dL (P=0.002,) and a greater proportion of smokers, 31% versus 16% (P=0.002). There were no statistically significant differences in plasma viscosity, fibrinogen, hematocrit, white blood cell count, platelet count, or sP-sel between the 2 subgroups. In multivariate analysis, vWF was a significant independent predictor for TOD. After 6 months of intensified management in 53 patients who entered the trial, there were significant reductions in systolic blood pressure, total cholesterol, hematocrit, plasma viscosity, sP-sel, and vWF (all P<0.01) but no significant change in fibrinogen. In conclusion, there is a relationship between TOD and endothelial damage/dysfunction in hypertension. Intensified management results in improvements in hemorheology, endothelial and platelet function.
authors.affiliation: Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, United Kingdom.
authors.forename: Charles G C
authors.initials: CG
authors.lastname: Spencer
authors.forename: David
authors.initials: D
authors.lastname: Gurney
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Blann
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Beevers
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use; D001539:Bendroflumethiazide / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003430:Cross-Sectional Studies; D004562:Electrocardiography; D005260:Female; D006400:Hematocrit; D018056:Hemorheology / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood / Q000187:drug effects*; D020913:Perindopril / Q000627:therapeutic use; D012044:Regression Analysis; D016037:Single-Blind Method; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D019007:P-Selectin; D014841:von Willebrand Factor; D017311:Amlodipine; D001262:Atenolol; D001539:Bendroflumethiazide; D020913:Perindopril