Relationship of homocysteine to markers of platelet and endothelial activation in "high risk" hypertensives: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial.
OBJECTIVE
To examine the relationship between plasma homocysteine (HCY) and rheological, endothelial and platelet markers in "high risk" hypertensive patients.


METHODS
Cross-sectional study.


METHODS
A total of 165 consecutive hypertensive patients (136 male; mean age 63 years (S.D. 8)) at high risk of cardiovascular disease who screened for inclusion in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) were studied along with 38 population normotensive healthy controls. We measured levels of plasma homocysteine [high pressure liquid chromatography (HPLC)], soluble P-selectin, a marker of platelet function, von Willebrand factor (vWF), an index of endothelial damage/dysfunction [both by ELISA] and fibrinogen (CLAUSS). The Framingham cardiovascular and cerebrovascular risk scores were calculated.


RESULTS
Hypertensives had significantly higher blood pressure (BP) [165/90(16/10) vs. 138/82(12/8) mm Hg, p<0.0001], sP-sel [54(44-67) vs. 45(35-57) ng/ml, p=0.002], vWF [133(34) vs. 110(28) IU/dl, p<0.0001], and fibrinogen [2.98(2.52-3.47) vs. 2.43(2.20-2.83)g/l, p=<0.0001]. Homocysteine were lower in our hypertensives compared with controls [8.7(6.9-11.2) vs. 10.5(8.5-13.1) micromol/l, p=0.005], but there were significant correlations between homocysteine levels and both calculated 10-year coronary heart disease risk (Spearman r=0.197, p=0.026) and stroke risk (r=0.210, p=0.018), using the Framingham equation. There was a positive correlation between plasma homocysteine and soluble P-selectin (r=0.180, p=0.025), which persisted in multiple linear regression analysis. There was no significant relationship between homocysteine and HCT, PV, or the endothelial marker, vWF.


CONCLUSIONS
Hypertensives demonstrate abnormalities of endothelial, platelet and rheological function. Homocysteine is related to both 10-year coronary heart disease risk and stroke risk, and is significantly correlated with soluble P-selectin, a marker of platelet activation, in hypertensives but only weakly or not at all to other thrombotic markers. Increased platelet activation as reflected by soluble P-selectin may be one mechanism by which hyperhomocysteinaemia confers an increased thrombotic risk in hypertension.
Spencer
Charles G C
CG
City Hospital Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, Birmingham B18 7QH, United Kingdom.
Martin
Steven C
SC
Felmeden
Dirk C
DC
Blann
Andrew D
AD
Beevers
Gareth D
GD
Lip
Gregory Y H
GY
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000209:etiology / Q000503:physiopathology; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000502:physiology*; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000503:physiopathology; D014841:von Willebrand Factor / Q000032:analysis
D015415:Biomarkers; D019007:P-Selectin; D014841:von Willebrand Factor; D006710:Homocysteine; D005340:Fibrinogen