CORRESPONDENCE: LETTER TO THE EDITOR
Resting Heart Rate and Cardiovascular Disease: The Beta-Blocker–Hypertension Paradox
Franz H. Messerli, MD, FACC* and
Sripal Bangalore, MD, MHA
* Hypertension Program, Division of Cardiology, Columbia University College of Physicians and Surgeons, St. Luke’s-Roosevelt Hospital Center, 1000 Tenth Avenue, Suite 3B-30, New York, New York 10025 (Email: fmesserli{at}aol.com).
The hypothesis of Fox et al. (1) of heart rate being an independent predictor of cardiovascular and all-cause mortality in people with and without diagnosed cardiovascular disease is convincing and supported by a solid body of evidence. Considerably less well documented is that pharmacologic heart rate slowing within the physiologic range will reduce cardiovascular events or, indeed, increase longevity. As Fox et al. (1) point out, it is likely that the beneficial effect of beta-blockers after myocardial infarction and in congestive heart failure is, at least to some extent, related to a reduction in heart rate. However, the opposite seems to be true in hypertension: we recently found a greater risk of cardiovascular events (all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, and heart failure, all p < 0.0001) with a lower heart rate in a meta-analysis of more than 60,000 patients in 9 large beta-blocker trials (2). Thus, the greater the heart rate reduction with beta-blockers, the greater the risk of cardiovascular events in hypertensive patients. The reason that drug-induced bradycardia is less beneficial than spontaneously occurring bradycardia may be related to the dyssynchrony of the reflected pulse wave and the outgoing pressure wave. Ideally, the reflected wave should return toward the heart during diastole to augment diastolic filling. If the wave returns earlier during the cardiac cycle, as is the case with pharmacologic heart rate slowing, it amplifies the outgoing pressure wave, thereby increasing systolic pressure. Indeed, findings from the CAFÉ (Conduit Artery Function Evaluation) (3) study, in which pulse-wave analysis was used to derive central aortic pressure, documented a pseudo-antihypertensive effect of the beta-blocker regimen (4). Despite identical brachial pressure in both treatment arms, central aortic systolic pressure was lowered significantly less well with atenolol than with amlodipine. Thus, pulse-wave dyssynchrony, secondary to heart rate slowing, may account for the beta-blocker–hypertension paradox. This would indicate that not all heart rate slowing is created equal—bradycardia induced by negative chronotropic drugs may not necessarily be as beneficial as bradycardia occurring spontaneously or being related to aerobic conditioning.
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Footnotes
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Please note: Dr. Messerli is an ad hoc consultant/speaker for Abbott, GlaxoSmithKline, Novartis, Pfizer, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Forest, Daiichi Sankyo, Sanofi-Aventis, Merck, and King Pharmaceuticals.
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References
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1. Fox K, Borer JS, Camm AJ, et al. Heart Rate Working Group Resting heart rate in cardiovascular disease J Am Coll Cardiol 2007;50:823-830.[Abstract/Free Full Text]2. Bangalore S, Sawhney S, Uretsky S, Messerli FH. Heart rate and anti-hypertensive therapy—Kjekshus hypothesis revisited(abstr) Circulation 2007;116:II654. 3. Williams B, Lacy PS, Thom SM, et al. CAFE Investigators; Anglo-Scandinavian Cardiac Outcomes Trial Investigators; CAFE Steering Committee and Writing Committee 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.[Abstract/Free Full Text] 4. Messerli FH, Williams B, Ritz E. Essential hypertension Lancet 2007;370:591-603.[CrossRef][Web of Science][Medline]
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