This Article Figures Only Full Text Full Text (PDF) View Related Cardiosmart Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (17) Citing Articles via Google Scholar Google Scholar Articles by Bangalore, S. Articles by Messerli, F. H. Search for Related Content PubMed Articles by Bangalore, S. Articles by Messerli, F. H. Related Collections Related Articles

CLINICAL RESEARCH: HYPERTENSION

Relation of Beta-Blocker–Induced Heart Rate Lowering and Cardioprotection in Hypertension

Department of Medicine, Division of Cardiology, St. Luke's Roosevelt Hospital and Columbia University College of Physicians and Surgeons, New York, New York

Manuscript received March 7, 2008; revised manuscript received June 3, 2008, accepted June 6, 2008.

^_* Reprint requests and correspondence: Dr. Franz H. Messerli, Hypertension Program, Division of Cardiology, St. Luke's-Roosevelt Hospital, Columbia University College of Physicians and Surgeons, 1000 10th Avenue, Suite 3B-30, New York, New York 10019 (Email: fmesserl{at}chpnet.org).

Objectives: The purpose of this study was to evaluate the role of heart rate reduction with beta-blockers on the risk of cardiovascular events in patients with hypertension.

Background: Resting heart rate has been shown to be a risk factor for cardiovascular morbidity and mortality in the general population and in patients with heart disease such as hypertension, myocardial infarction, and heart failure. Conversely, pharmacological reduction of heart rate is beneficial for patients with heart disease. However, the role of pharmacological reduction of heart rate using beta-blockers in preventing cardiovascular events in patients with hypertension is not known.

Methods: We conducted a MEDLINE/EMBASE/CENTRAL database search of studies from 1966 to May 2008. We included randomized controlled trials that evaluated beta-blockers as first-line therapy for hypertension with follow-up for at least 1 year and with data on heart rate. We extracted the baseline characteristics, the blood pressure response, heart rate at the baseline and end of trial, and cardiovascular outcomes from each trial.

Results: Of 22 randomized controlled trials evaluating beta-blockers for hypertension, 9 studies reported heart rate data. The 9 studies evaluated 34,096 patients taking beta-blockers against 30,139 patients taking other antihypertensive agents and 3,987 patients receiving placebo. Paradoxically, a lower heart rate (as attained in the beta-blocker group at study end) was associated with a greater risk for the end points of all-cause mortality (r = –0.51; p < 0.0001), cardiovascular mortality (r = –0.61; p < 0.0001), myocardial infarction (r = –0.85; p < 0.0001), stroke (r = –0.20; p = 0.06), or heart failure (r = –0.64; p < 0.0001). The same was true when the heart rate difference between the 2 treatment modalities at the end of the study was compared with the relative risk reduction for cardiovascular events.

Conclusions: In contrast to patients with myocardial infarction and heart failure, beta-blocker–associated reduction in heart rate increased the risk of cardiovascular events and death for hypertensive patients.

Key Words: beta-blockers • heart rate • hypertension

Abbreviations and Acronyms   CAD = coronary artery disease   CI = confidence interval   MI = myocardial infarction   RCT = randomized controlled trial   RR = relative risk

Related Articles

Beta-Blockers in Hypertension: Adding Insult to Injury

Norman M. Kaplan
J. Am. Coll. Cardiol. 2008 52: 1490-1491. [Full Text] [PDF]

This article has been cited by other articles:

				R. A. Phillips Is the relationship between Beta-blocker-induced heart rate lowering and cardiovascular outcomes the result of confounding by indication? J. Am. Coll. Cardiol., June 2, 2009; 53(22): 2101 - 2101. [Full Text] [PDF]

				J. R. Cockcroft Atenolol is dead: long live Beta-blockade. J. Am. Coll. Cardiol., June 2, 2009; 53(22): 2102 - 2102. [Full Text] [PDF]

				S. Laurent and P. Boutouyrie Beta-blocker-induced heart rate reduction too simplistic to explain the deleterious effects of Beta-blockers. J. Am. Coll. Cardiol., June 2, 2009; 53(22): 2103 - 2104. [Full Text] [PDF]

				S. S. Khan Beta-blocker-induced heart rate lowering, cardioprotection, and hypertension. J. Am. Coll. Cardiol., June 2, 2009; 53(22): 2104 - 2105. [Full Text] [PDF]

				G. Fragasso, M. Cera, and A. Margonato Different metabolic effects of selective and nonselective Beta-blockers rather than mere heart rate reduction may be the mechanisms by which Beta-blockade prevents cardiovascular events. J. Am. Coll. Cardiol., June 2, 2009; 53(22): 2105 - 2105. [Full Text] [PDF]

				F. H. Messerli and S. Bangalore Reply. J. Am. Coll. Cardiol., June 2, 2009; 53(22): 2106 - 2107. [Full Text] [PDF]

				I. Aursnes and J.-B. Osnes Atenolol versus other Beta-adrenergic blockers. J. Am. Coll. Cardiol., June 2, 2009; 53(22): 2101 - 2102. [Full Text] [PDF]

				V. K. Gupta Beta-blockers, hypertension, and randomized controlled trials: science and sensibility. J. Am. Coll. Cardiol., June 2, 2009; 53(22): 2102 - 2103. [Full Text] [PDF]

				J. M. Cruickshank Beta-blockers and hypertension. J. Am. Coll. Cardiol., June 2, 2009; 53(22): 2105 - 2106. [Full Text] [PDF]

				J.-C. Tardif Heart rate as a treatable cardiovascular risk factor Br. Med. Bull., June 1, 2009; 90(1): 71 - 84. [Abstract] [Full Text] [PDF]

				R. Gopinathannair, R. M. Sullivan, and B. Olshansky Slower Heart Rates for Healthy Hearts: Time to Redefine Tachycardia? Circ Arrhythmia Electrophysiol, December 1, 2008; 1(5): 321 - 323. [Full Text] [PDF]

				N. M. Kaplan Beta-Blockers in Hypertension: Adding Insult to Injury J. Am. Coll. Cardiol., October 28, 2008; 52(18): 1490 - 1491. [Full Text] [PDF]