title: Platelet aggregation in whole blood is a paradoxical predictor of ischaemic stroke: Caerphilly Prospective Study revisited.
abstract: The Caerphilly Prospective Study demonstrates a paradoxical association of increased ischaemic stroke risk with decreased whole blood adenosine diphosphate (ADP) induced platelet sensitivity. A reanalysis of this association examines whether other haematological indices and prevalent disease at baseline may explain this finding. There were 1506 men free of clinical cardiovascular disease at baseline, with 85 men manifesting a first ischaemic stroke event over 8.3 years of follow-up in this population-based prospective cohort study. Using two different approaches, the paradoxical findings are confirmed and associations are slightly stronger after accounting for red cell, platelet, and white cell indices. A U-shaped relation of stroke with platelet count is noted. These findings are consistent with the existence of sub-clinical endothelial disease and compensatory mechanisms down-regulating ADP-induced aggregation sensitivity. They support an allostasis model of causality for understanding the paradox. A public health approach to prevention could have measurable impact if intervention strategies can be developed to alter early stages of disease appropriate to such mechanisms of causation.
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA. dsharp@cdc.gov
authors.forename: D S
authors.initials: DS
authors.lastname: Sharp
authors.forename: Y
authors.initials: Y
authors.lastname: Ben-Shlomo
authors.forename: A D
authors.initials: AD
authors.lastname: Beswick
authors.forename: M E
authors.initials: ME
authors.lastname: Andrew
authors.forename: P C
authors.initials: PC
authors.lastname: Elwood
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D001780:Blood Coagulation Tests / Q000379:methods; D001792:Blood Platelets / Q000502:physiology; D002545:Brain Ischemia / Q000097:blood* / Q000453:epidemiology*; D015984:Causality; D015331:Cohort Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D010865:Pilot Projects; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D011446:Prospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D020521:Stroke / Q000097:blood* / Q000453:epidemiology*; D014852:Wales / Q000453:epidemiology
chemical_list: D000244:Adenosine Diphosphate