doi: 10.1161/CIRCULATIONAHA.107.692970
(Circulation. 2007;115:1973-1974.)
© 2007 American Heart Association, Inc.
Editorial |
The Obese Hypertensive
The Weight of Evidence Against ß-Blockers
From the Department of Cardiovascular Sciences, University of Leicester School of Medicine, Leicester, UK.
Correspondence to Bryan Williams, MD, FRCP, FAHA, Professor of Medicine, Department of Cardiovascular Sciences, Clinical Sciences Bldg, Leicester Royal Infirmary, PO Box 65, Leicester, LE2 7LX, UK. E-mail bw17{at}le.ac.uk
Key Words: Editorials • blood pressure • hypertension • obesity • beta-blockers
It has long been accepted that the cardiovascular risk burden of hypertension is attributable to more than blood pressure itself. Many patients with hypertension have a constellation of risk factors that add to their risk, notably features of the metabolic syndrome. The link between obesity and the metabolic syndrome is well recognized.1 However, obesity also is associated with an increased prevalence of hypertension.2 Although body mass index often is used to define obesity, visceral adiposity is more important in defining the relationship between blood pressure and obesity. Studies using magnetic resonance imaging to accurately quantify the distribution of body fat have shown that in untreated hypertensive men, fat preferentially accumulates intra-abdominally and intrathoracically and that the magnitude of visceral adiposity is quantitatively related to the elevation in blood pressure.3 It is important to note that this link between adiposity and blood pressure is observable from early childhood and is a key predictor of the likelihood of developing overt hypertension.4 Visceral fat accumulation in people with hypertension also underpins the link between hypertension and the metabolic syndrome and ultimately the increased risk of people with hypertension developing diabetes mellitus. Consequently, lifestyle interventions, including weight loss, are an important means of reducing blood pressure, the associated metabolic disturbances, and the risk of progression to diabetes.1,5
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The preferred strategy to reduce body weight toward the ideal in people with hypertension is lifestyle modification. However, not uncommonly, this approach fails to achieve its objectives, and adjunctive therapeutic interventions designed to facilitate weight loss have been developed. With regard to therapy for people with hypertension, the potential exists for some blood pressure–lowering medications to influence body weight, and concern in this regard has focused primarily on ß-blockers and their potential to promote weight gain or to hinder weight loss.6
In this issue of Circulation, Scholze and colleagues7 have made an important contribution to the debate about the preferred treatment of the obese hypertensive patient. They have evaluated the interaction between 2 different blood pressure–lowering strategies and sibutramine, a selective serotonin and norepinephrine reuptake inhibitor that can promote weight loss. This study is important for 2 reasons. First, there have been concerns that sibutramine might actually increase blood pressure because of its mode of action as a monoamine reuptake inhibitor and thereby reduce the efficiency of blood pressure–lowering medication. Second, the use of a weight loss–promoting drug provides a controlled stimulus for weight loss in obese hypertensive patients that allows the impact of different blood pressure–lowering agents on weight loss and associated metabolic parameters to be evaluated and quantified in a controlled way over a short period of time.
In a prospective 16-week, double-blind, placebo-controlled, randomized study of obese hypertensive patients, as expected, sibutramine treatment was more effective than placebo at reducing body weight, body mass index, and waist circumference. Blood pressure lowering, especially diastolic blood pressure, with the antihypertensive therapies was slightly attenuated by sibutramine treatment compared with placebo, but this did not reach statistical significance. However, this study is relatively small and of short duration. Whether the effect of sibutramine on blood pressure would be clinically significant in some patients cannot be confidently excluded by this study, and the small average effects observed do not exclude the possibility that more significant changes could occur in individual patients, thereby mandating the need for careful long-term blood pressure monitoring in all patients when this treatment is used to promote weight loss.
The study also examined the interaction between sibutramine and blood pressure lowering on weight loss and metabolic parameters. Two different blood pressure–lowering strategies were studied: conventional therapy involving combinations of ß-blocker and thiazide diuretic treatment and more contemporary blood pressure–lowering therapy with 2 different calcium channel blocker/angiotensin-converting enzyme inhibitor–based treatments. Blood pressure–lowering efficacy was similar between these 2 treatment strategies. It is important to note, however, sibutramine-induced weight loss was markedly attenuated in the ß-blocker/thiazide–treated patients. Moreover, the sibutramine-induced improvements in glucose tolerance also were markedly attenuated by the ß-blocker/thiazide diuretic treatment. These findings are important because they lend strong support to the perception from previous meta-analyses that ß-blocker–based treatments in particular may promote weight gain6 and that ß-blocker/thiazide–based treatments enhance the risk of developing diabetes mellitus.8,9 This study also suggests that the basis for these observations lies with a specific effect of ß-blocker–based treatment on the accumulation of visceral adiposity and the associated features of the metabolic syndrome. The biological basis for these findings was not specifically addressed by the study. Nevertheless, in previous blood pressure–lowering trials, there has been no sign suggesting an effect of thiazide-type diuretics on inducing weight gain, even though they may have contributed to the metabolic disturbances observed, especially glucose intolerance. In contrast, evidence exists that ß-blockers may promote weight gain and metabolic disturbances, most likely in part because of the potential for ß-blocker therapy to reduce physical activity and muscle blood flow. Although the biological basis for these findings is open to speculation and awaits further exploration, their importance for clinical practice is without question. Mindful of the fact that visceral fat accumulation underpins the link between obesity, hypertension, and the attendant metabolic syndrome, it seems illogical to advocate a ß-blocker–based treatment strategy for the routine treatment of hypertension with the knowledge that it will undermine the ability to redress the associated metabolic disturbances, whether by lifestyle interventions or drug therapy.
These findings add to a growing list of concerns about the efficiency and cost effectiveness of ß-blockers as a preferred routine treatment for hypertension.10–13 Previous studies and meta-analyses have demonstrated that ß-blocker–based treatments are no more effective than any other class of blood pressure–lowering therapy at preventing major cardiovascular events and are significantly less effective at preventing stroke in people with hypertension.10–15 ß-Blocker–based treatments also have a less beneficial effect than alternative treatments on central aortic pressures and hemodynamics,16 and they are more likely to result in the development of diabetes mellitus, especially when combined with thiazide-type diuretics.8,9 Moreover, in a formal cost-effectiveness analysis, ß-blockers were the least cost-effective treatment option for hypertension, despite their relatively modest cost.17 The national treatment guidelines in the United Kingdom were recently updated to reflect these findings and recommend that ß-blockers should no longer be a preferred routine initial treatment for hypertension unless there are compelling indications, and even then, they should not usually be combined with a thiazide-type diuretic.17 The findings of the study of Scholze and colleagues7 add to the weight of evidence against ß-blocker treatment for hypertension, especially those with obesity.
Finally, interest is growing in the use of medication such as sibutramine to offset the weight gain and metabolic disturbances associated with modern lifestyles. The effect of these therapies on body weight relative to the rotund baseline of most patients in studies seems modest at best. It is clear that weight loss therapeutics will never be a substitute for effective lifestyle modification. Furthermore, the longer-term safety and effectiveness of these weight-modifying interventions at reducing cardiovascular events and improving clinical outcomes need to be evaluated. In the meantime, we should ensure that the treatment of traditional risk factors such as blood pressure does not hinder the objectives of lifestyle intervention and the lowering of blood pressure itself.
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Acknowledgments |
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Disclosures
None.
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Footnotes |
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The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.
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References |
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- Sironi AM, Gastaldelli A, Mari A, Ciociaro D, Postano V, Buzzigoli E, Ghione S, Turchi S, Lombardi M, Ferrannini E. Visceral fat in hypertension. Hypertension. 2004; 44: 127–133.
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