Prognostic value of plasma soluble P-selectin and von Willebrand factor as indices of platelet activation and endothelial damage/dysfunction in high-risk patients with hypertension: a sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial.
BACKGROUND
Abnormal levels of prothrombotic markers have been described in hypertension, but no such marker has yet been shown to reliably predict cardiovascular outcomes in hypertension. We hypothesized that raised circulating levels of soluble P-selectin (sP-sel, an index of platelet activation) and/or von Willebrand factor (vWF, an index of endothelial damage/dysfunction) would predict vascular events in patients treated for cardiovascular risk.


METHODS
We measured vWF and sP-sel levels by an ELISA in 234 hypertensive participants with no prior cardiovascular events who were participating in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Plasma vWF and sP-sel levels were related to the subsequent cardiovascular events over a mean (SD) follow-up period of 59.6 (19) months.


RESULTS
Plasma sP-sel was a significant predictor of myocardial infarction (P = 0.03), with the greatest risk amongst those with the highest sP-sel levels. sP-sel did not predict cerebrovascular events (P = 0.53) or composite cardiovascular events (P = 0.06). No significant relationships were found between vWF levels and outcomes. There was no relationship to the presence or absence of diabetes mellitus (DM) at baseline or subsequent development of DM during the follow-up period.


CONCLUSIONS
Among 'high-risk' patients with hypertension, raised levels of sP-sel (platelet activation) were predictive of myocardial infarction. Levels of vWF (endothelial damage/dysfunction) were not associated with coronary events and neither marker predicted cerebrovascular or composite cardiovascular endpoints. Platelets (or P-selectin) might represent a target for novel therapies or an adjunctive aid to risk stratification in the setting of hypertension.
Varughese
G I
GI
Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK.
Patel
J V
JV
Tomson
J
J
Blann
A D
AD
Hughes
E A
EA
Lip
G Y H
GY
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood*; D015539:Platelet Activation; D011379:Prognosis; D012307:Risk Factors; D014841:von Willebrand Factor / Q000032:analysis*
D015415:Biomarkers; D019007:P-Selectin; D014841:von Willebrand Factor