RISK-FACTORS FOR CAROTID ATHEROSCLEROSIS AND PLATELET ACTIVATION

Thromboxane A(2) biosynthesis was studied in healthy subjects, in pati ents in whom the extent of carotid atherosclerosis was determined, and in patients receiving chronic aspirin treatment, to determine what fa ctors activate platelets to develop carotid atherosclerosis. Urinary 1 1-dehydrothromboxane B-2, a major metabolite of thromboxane A(2), was measured by radioimmunoassay after purification by reverse-phase HPLC. The extent of carotid atherosclerosis was determined by real-time B-m ode ultrasonography. The severity of carotid atherosclerosis in each s ubject was evaluated by plaque score, which was computed by summing th e maximum thickness of plaque measured in millimeters. Urinary excreti on of 11-dehydrothromboxane B-2 in healthy subjects was higher (P < 0. 01) in cigarette smokers (1063 +/- 244 ng/g creatinine) than in non-sm okers (815 +/- 183 ng/g creatinine). Aspirin significantly suppressed 11-dehydrothromboxane B-2 excretion (266 +/- 114 ng/g creatinine). In the 24 patients in whom the plaque score was measured, multivariate an alysis indicated a significant positive correlation between urinary ex cretion of 11-dehydrothromboxane B-2 and plaque score, age, smoking an d hypercholesteremia. Our results indicate that risk factors such as a ge, hypercholesteremia, atherosclerosis and smoking activate platelets in vivo to develop carotid atherosclerosis.