Author + information
- Franz H. Messerli, MD,
- Stefano F. Rimoldi, MD,
- Sripal Bangalore, MD, MHA∗ (, )
- Chirag Bavishi, MD, MPH and
- Stephane Laurent, MD, PhD
- ↵∗The Leon H. Charney Division of Cardiology, New York University School of Medicine, 550 First Avenue, New York, New York 10016
We appreciate Dr. Palatini’s interest in our review paper and would like to respond by making the following 4 points. First, we agree that the greater augmentation index associated with a lower heart rate implies but this cannot be translated “tout court” into increased arterial stiffness. The increase in augmentation index and stroke volume are simply the hemodynamic repercussion of a slower heart rate. Whether or not they will ultimately give rise to increase in arterial stiffness may depend, as Dr. Palatini states, on “many other variables.”
Second, when analyzing the effects of beta-blockers on the arterial wall, we should remember that these drugs are not pure negative chronotropic agents; they also block the renin–angiotensin system and interfere with sympathetic stimulation. The overall effect on the arterial tree depends on the interplay of these pharmacological mechanisms. Suffice to say that Schiffrin documented by using gluteal subcutaneous biopsies that treatment with the calcium channel blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers corrected altered resistance artery structure and tended to improve endothelial function in essential hypertensive patients after 1 year, whereas similar good control of blood pressure with the beta-blocker atenolol did not (1,2).
Third, we also should recall that the CAFÉ (Conduit Artery Function Evaluation) study documented a highly significant inverse relationship between heart rate and central aortic systolic and pulse pressures (p < 0.001), indicating that heart rate reduction with beta-blockers was the major mechanism accounting for less effective central aortic pressure reduction per unit change in brachial pressure (3).
Finally, given that ivabradine is a “pure” negative chronotropic drug, it seems somewhat difficult to explain its complete lack of efficacy in 2 large, randomized trials of patients with stable coronary heart disease unless one accepts that pharmacological heart rate lowering may indeed not always be beneficial.
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Deepak L. Bhatt, MD, MPH, served as Guest Editor-in-Chief for this paper. George Bakris, MD, served as Guest Editor for this paper.
- American College of Cardiology Foundation
- Schiffrin E.L.,
- Pu Q.,
- Park J.B.
- Williams B.,
- Lacy P.S.