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We examined the relation between cardiovascular reactivity (the response of the cardiovascular system to psychological stress) and the severity and progression of carotid atherosclerosis.Using duplex ultrasonography, we measured the change in the area of all detectable plaques in the extracranial carotid arteries during 2 years. Cardiovascular reactivity was assessed by measuring changes in hemodynamics during a frustrating cognitive task (the Stroop Color Word Interference Task). Established risk factors for atherosclerosis were measured by interviewing patients, a physical examination, and blood assays for 351 subjects with a wide range of types of atherosclerotic disease.Atherosclerotic plaques were present in the carotid arteries of 273 (78%) subjects. In a forward stepwise multiple regression analysis, it was found that greater age (β = 0.46), a history of hypertension (β = 0.20), use of lipid level-lowering agents (β = 0.18), a longer history of smoking (β = 0.13), a larger cholesterol: high-density lipoprotein ratio (β = 0.13), a smaller change in heart rate during the task (β = −0.12), and a higher resting systolic blood pressure (SBP; β = 0.11) were associated significantly with a greater plaque area (R2 = 0.35). In 136 untreated subjects who were followed up for 2 years, a greater change in SBP during the task (b = 0.28), a higher total cholesterol: high-density lipoprotein ratio (β = 0.23), a shorter resting preejection period (β = −0.19), and a lower body mass index (β = −0.17) were significant predictors of the change in atherosclerosis, after controlling for age and initial plaque area in a stepwise multiple regression analysis (R2 = 0.24).These results support the hypothesis that hemodynamic responses under conditions of mental stress may influence the progression of atherosclerosis.