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The significance of β-blockers in the treatment of cardiovascular diseases is well established. The effect of vasodilating β-blockers on endothelial function and prothrombotic state has not been investigated.The study comprised 550 consecutive patients with uncomplicated essential hypertension. They were treated with celiprolol, carvedilol or nebivolol monotherapy (171, 179, and 200 patients, respectively), achieving comparable blood pressure reduction. Plasma levels of fibrinogen and homocystine and serum levels of plasminogen activator inhibitor-1 (PAI-1) were obtained before and 6 months after initiation of treatment.The three drugs differentiated in regard to homocystine (P < .00001) and fibrinogen level changes (P = .00003), but not (P = NS) in PAI-1 change. In smokers, differentiation was found in all three parameters (P = .0002, P = .001, and P = .006 for fibrinogen, PAI-1, and homocystine, respectively), but in nonsmokers differentiation was found only in homocystine change (P = .00003). In smokers, fibrinogen, PAI-1, and homocystine were reduced more (P = .002, P = .0009, and P <.0001, respectively) than in nonsmokers in the whole study cohort. The effect of nebivolol was more prominent in smokers than nonsmokers in reducing all three parameters (P = .0001, .003, and .003, respectively), whereas in celiprolol and carvedilol-treated groups, differentiation between smokers and nonsmokers was significant (P = .00003 and .01, respectively) only in homocystine level change.In hypertensive smokers, nebivolol resulted in a significant decrease of plasma PAI-1, fibrinogen and homocystine. Celiprolol also significantly affected these parameters but to a lesser degree, whereas carvedilol had no significant favorable action. In nonsmokers, homocystine was reduced significantly by nebivolol. We conclude that smoking status should be a determinant of antihypertensive treatment choice. Am J Hypertens 2004;17:582-589 © 2004 American Journal of Hypertension, Ltd.