Letter by Nieminen et al Regarding Article, “Differential Impact of Blood Pressure-Lowering Drugs on Central Aortic Pressure and Clinical Outcomes: Principal Results of the Conduit Artery Function Evaluation (CAFE) Study”
To the Editor:
The interesting article by Williams et al1 convincingly shows that treatments based on atenolol and amlodipine differ substantially in their influences on central aortic pressures even in long-term treatment, despite having similar effects on brachial blood pressures. The authors conclude that this phenomenon is due to differences in the timing of systolic ejection caused by lower heart rate during treatment with the β-blocker atenolol. This mechanism certainly has merit.
However, there is another physiological and pharmacological factor to be considered: Because a β-blocker slows down heart rate, the filling time of the left ventricle increases, leading to larger end-diastolic volume and preload. According to the Frank-Starling law, the higher the preload, the larger the stroke volume (SV). This suggests that β-blocker therapy would increase SV. This has indeed been demonstrated particularly in using β-blockers with vasodilatory properties—such as nebivolol2 or carvedilol3—but also using, for example, atenolol4 and metoprolol.3 Therefore, the enhancement of SV occurs despite the slightly negative inotropic effect of the β-blockers.
On the other hand, SV is a well-known determinant of pulse pressure (PP)5: Given a constant compliance, elevation of PP is secondary to a rise in SV and vice versa. In the case of atenolol and the consequential increase in SV, the increase in central aortic PP and the changes in the corresponding pressure waveform are probably a combination of the enhanced direct outflow from the heart and stronger reflected pressure waves. We believe that this simple mechanism partially explains the differential effect of amlodipine and atenolol on aortic pressures.
Williams B, Lacy PS, Thom SM, Cruickshank K, Stanton A, Collier D, Hughes AD, Thurston H, O’Rourke M. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) Study. Circulation. 2006; 113: 1213–1225.
Metra M, Giubbini R, Nodari S, Boldi E, Modena MG, Dei Cas L. Differential effects of beta-blockers in patients with heart failure: a prospective, randomized, double-blind comparison of the long-term effects of metoprolol versus carvedilol. Circulation. 2000; 102: 546–551.
Mier CM, Domenick MA, Wilmore JH. Changes in stroke volume with beta-blockade before and after 10 days of exercise training in men and women. J Appl Physiol. 1997; 83: 1660–1665.