THE IMPACT OF THIRD-GENERATION BETA-BLOCKER ANTIHYPERTENSIVE TREATMENT ON ENDOTHELIAL FUNCTION AND THE PROTHROMBOTIC STATUS. EFFECTS OF SMOKING

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 homocysteine 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 homocysteine (p<0,00001) and fibrinogen level changes (p=0,00003), but not (p=NS) in PAI-1 change. In smokers, differentiation was found in all three parameters (p=0,0002, p=0,001, and p=0,006 for fibrinogen, PAI-1, and homocysteine, respectively), but in non-smokers differentiation was found only in homocysteine change (p=0,00003). In smokers, fibrinogen, PAI-1, and homocysteine were reduced more (p=0,002, p=0,0009, and p<0,0001, respectively) than in non-smokers in the whole study cohort. The effect of nebivolol was more prominent in smokers than non-smokers in reducing all three parameters (p=0,0001, p=0,003, and p=0,003, respectively), whereas in celiprolol and carvedilol-treated groups, differentiation between smokers and non-smokers was significant (p=0,00003 and p=0,01, respectively) only in homocysteine level change. In hypertensive smokers, nebivolol resulted in a significant decrease of plasma PAI-1, fibrinogen, and homocysteine. Celiprolol also significantly affected these parameters but to a lesser degree, whereas carvedilol had no significant favourable action. In non-smokers, homocysteine was reduced significantly by nebivolol. We conclude that smoking status should be a determinant of antihypertensive treatment choice.

Hypertension, third-generation beta-blockers, endothelial function, prothrombotic state, smoking

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