Evidence for allostasis: how decreased platelet sensitivity predicts increased stroke risk.
Sharp-DS; Ben-Shlomo-Y; Beswick-AD; Andrew-ME; Elwood-PC
Am J Epidemiol 2005 Jun; 161(11)(Suppl):S23
The Caerphilly Prospective Study demonstrates a paradoxical association of increased thromboembolic stroke risk with decreased whole blood adenosine diphosphate (ADP) induced platelet sensitivity (Br J Hematol 2001; 112:514-520). A new analysis of this association examines whether other hematological indices and prevalent disease at baseline explain this finding. Of 1,506 men free of cardiovascular disease at baseline, 85 manifest a thromboembolic stroke event over 8.3 years of follow-up. The paradoxical findings are confirmed and associations are slightly stronger after accounting for red cell, paltelet, and white cell indices; age-adjusted relative risks increasing from 1.41 [95% Confidence Interval: 1.05, 1.89] to 1.54 [1.11, 2.14]. A U-shaped relation of stroke with platelet count is also noted. In contrast, 55 men prevalent for thromboemoblic stroke at baseline demonstrate increased platelet sensitive. These new findings are consistent with the existence of sub-clinical endothelial disease and established compensatory mechanisms down-regulating ADP-induced platelet aggregation sensitivity. They support an allostasis model of causality for understanding the paradox. A public health approach to prevention could have measureable impact if intervention strategies can be developed to alter early stages of disease appropriate to such mechanisms of causation.
Risk-factors; Risk-analysis; Sensitivity-testing; Demographic-characteristics; Age-factors; Sex-factors; Diseases; Disease-prevention; Cardiovascular-system-disorders
American Journal of Epidemiology