0
Review Article |

Long-term Effects of Weight-Reducing Interventions in Hypertensive Patients:  Systematic Review and Meta-analysis FREE

Karl Horvath, MD; Klaus Jeitler, MD; Ulrich Siering, Dipl Soz; Anne K. Stich, Dipl Soz-Päd; Guido Skipka, DrRerNat; Thomas W. Gratzer, MD; Andrea Siebenhofer, MD
[+] Author Affiliations

Author Affiliations: EBM Review Center, Department of Internal Medicine, Medical University of Graz, Graz, Austria (Drs Horvath, Jeitler, Gratzer, and Siebenhofer); German Institute for Quality and Efficiency in Health Care, Cologne, Germany (Drs Siering, Stich, and Skipka); and Deutsche Krebshilfe-German Cancer Aid, Bonn, Germany (Dr Siering).


Arch Intern Med. 2008;168(6):571-580. doi:10.1001/archinte.168.6.571.
Text Size: A A A
Published online

Weight loss is recommended in all major guidelines for antihypertensive therapy. We searched for randomized controlled trials investigating the effects of weight-reducing diets, pharmacologic substances, and invasive interventions for weight reduction on patient-relevant end points and blood pressure (BP) in patients with essential hypertension. No information on the effects on patient-relevant end points was available. Patients assigned to weight loss diets, orlistat, or sibutramine reduced their body weight more effectively than did patients in the usual care/placebo groups. Reduction of BP was higher in patients treated with weight loss diets (systolic BP [SBP]: weighted mean difference [WMD], −6.3 mm Hg; diastolic BP [DBP]: WMD, −3.4 mm Hg) or orlistat (SBP: WMD, −2.5 mm Hg; DBP: WMD, −2.0 mm Hg). Systolic BP increased with sibutramine treatment (WMD, 3.2 mm Hg). In patients with essential hypertension, therapy with a weight loss diet or orlistat resulted in reductions in body weight and BP. Although sibutramine treatment reduced body weight, it did not lower BP.

Figures in this Article

Globally, cardiovascular diseases (CVDs) account for 13% of the disease burden in adults and for approximately half of the deaths caused by noncommunicable diseases, that is, 16.7 million. In developed countries, heart disease and stroke are the first and second leading causes of death in adults and together are responsible for 36% of all deaths. Furthermore, the mortality and disease burden resulting from CVD are rapidly increasing in developing regions.1 Among the major CVD risk factors is high blood pressure (BP). High BP is estimated to lead to more than 7 million deaths each year, approximately 13% of the total deaths worldwide.2 Lowering BP levels in hypertensive patients has been shown to be a very effective means of reducing patients' cardiovascular risk, with a significant reduction in cardiovascular morbidity and mortality.3

Consistently, epidemiologic investigations have found an association between high BP and different lifestyles, excess body weight among them. Weight reduction is recommended in major guidelines as an initial intervention in the treatment of hypertensive patients.4,5 Among the possible means of reducing body weight are lifestyle modifications and pharmacologic and invasive interventions.

The review question was to assess the long-term effects of (1) dietary interventions intended to reduce body weight, (2) pharmacologically induced reduction in body weight, and (3) reduction of body weight through invasive interventions on all causes of death, cardiovascular morbidity, adverse events, and BP in people with essential hypertension.

ELIGIBILITY CRITERIA

To be included in this meta-analysis, trials were required to use a randomized controlled design; to compare dietary, pharmacologic, or invasive interventions for weight loss with placebo or usual care; and to have follow-up of at least 24 weeks. Combinations of different nonpharmacologic interventions for reducing BP without the possibility of analyzing the different interventions were excluded. In the case of an additional active care (eg, antihypertensive medication), this co-therapy also had to be a component of the comparison group. To be considered, trials had to include patients with essential hypertension aged 18 years or older (excluding pregnant women) and had to report on at least 1 of the following outcomes: mortality, cardiovascular outcomes, adverse events, and BP effects. Publication language had to be English, German, Dutch, French, Italian, Portuguese, or Spanish.

IDENTIFICATION AND SELECTION OF TRIALS

An initial search was performed in June 2006 in MEDLINE, EMBASE, the Cochrane databases, BIOSIS, and CINAHL and in the reference lists of retrieved relevant articles and overviews. Also, study registries and the Internet sites of the European Agency for the Evaluation of Medicinal Products and the Food and Drug Administration were searched. Companies producing sibutramine hydrochloride and orlistat and authors of relevant articles were contacted. In March 2007, we updated the search and extended it to include rimonabant. The updated search was limited to the electronic databases MEDLINE, EMBASE, and CENTRAL.

OUTCOME MEASURES

Outcomes of primary interest were total mortality, cardiovascular morbidity, and adverse events. Other analyzed outcomes were duration and magnitude of BP and body weight reduction.

STUDY SELECTION AND QUALITY ASSESSMENT

Two of us (K.H., K.J., T.W.G., and/or A.S.) independently screened the title, abstract, and key words of each reference identified by the search and applied the inclusion and exclusion criteria. The same procedure was applied to references retrieved for more detailed evaluation. Differences between reviewers were resolved by discussion or a third reviewer (K.H., K.J., T.W.G., or A.S.). Data on quality, patient characteristics, interventions, and relevant outcomes were abstracted by 2 reviewers (K.H., K.J., T.W.G., and/or A.S.) independently.

Quality assessment was based on the adequacy of randomization; allocation of concealment; blinding of participants, study personnel, and outcome assessors; comparability of patients in the different treatment groups for prognostically relevant factors at baseline; follow-up and handling of withdrawals and dropouts in the analyses; statistical methods; and consistency of reporting. Accordingly, the methodological quality of the included studies was graded as no methodological deficiencies detectable (A), slight methodological deficiencies detectable (B), or serious methodological deficiencies detectable (C).

STATISTICAL ANALYSIS

Weighted mean differences (WMDs) were calculated for the changes in BP and body weight. A random-effects model was used for the meta-analyses. Standard deviations were approximated on the basis of P values and, if P values were not available, sample sizes. Heterogeneity between trials was assessed using Higgins I2, which describes the percentage of the variability in effect estimates due to heterogeneity. In the case of substantial heterogeneity (Higgins I2 > 50%),6 we planned to perform sensitivity analyses and subgroup analyses for the following items: study quality, per-protocol vs intention-to-treat analyses, sex, age, body mass index, concomitant diseases, ethnicity, BP at baseline, BP goals, concomitant antihypertensive therapy, and socioeconomic status. However, owing to the low number of included trials in the different meta-analyses and the lack of information on most of these items, we could not perform formal sensitivity analyses. A formal statistical test on publication bias was not meaningful because of the low number of included trials.7

TRIAL FLOW

Figure 1 shows the number of trials (1) identified, (2) excluded for various reasons, and (3) included in the systematic review. The XENDOS study810 was included in this review only after additional information was made available through the manufacturer (Hoffmann-LaRoche AG, Basel, Switzerland). This information is publicly available in the Institute for Quality and Efficiency in Health Care report8 on this topic.

Place holder to copy figure label and caption
Figure 1.

Flow diagram of the systematic review. EMEA indicates European Agency for the Evaluation of Medicinal Products; FDA, Food and Drug Administration; and RCT, randomized controlled trial.

Graphic Jump Location

Seven studies (38 publications) investigated dietary interventions. In 8 studies (10 publications), pharmacologic interventions (orlistat or sibutramine) were compared with placebo. No studies examining surgical interventions or rimonabant satisfying the inclusion criteria were found, mainly because studies were not randomized, had a duration of less than 24 weeks, or did not allow for extraction of results for hypertensive patients.

DIETARY INTERVENTION STUDIES
Trial Characteristics and Quality

The 7 studies (Croft et al,11 the Dietary Intervention Study of Hypertension [DISH],1214 Jalkanen,15 the Oslo Diet and Exercise Study [ODES],1624 Ruvolo et al,25 the Trial of Antihypertensive Interventions and Management [TAIM],2637 and the Trial of Nonpharmacologic Interventions in the Elderly [TONE]3848) comparing a dietary intervention for reducing body weight with usual care included a total of 1632 patients. Follow-up lasted 6 to 36 months, and the mean age of patients ranged from 45 to 66 years. For results on study quality, see Table 1.

Results of Data Synthesis

Only TONE3848 was designed to evaluate the effects of dietary weight loss vs no such diet on a combined end point, including cardiovascular complications. After 30 months, the hazard ratio for patients in the dietary group to reach the combined end point, consisting of the necessity of reinstating antihypertensive therapy and severe cardiovascular complications, was 0.70 (95% confidence interval [CI], 0.57 to 0.87) compared with patients in the usual care group. No information on possible adverse effects of the different dietary interventions was reported in any publications of the relevant trials.

Based on their design, the reported outcomes, and data, only the studies by Croft et al11 and ODES1624 could be included in a meta-analysis on systolic BP (SBP). The meta-analysis found a significant difference in the reduction of SBP in favor of dietary interventions: WMD, −6.26 mm Hg (95% CI, −9.82 to −2.70 mm Hg) (I2 = 0%) (Figure 2A). For diastolic BP (DBP), the Croft et al,11 ODES,1624 and TAIM2637 studies were incorporated into the meta-analysis, showing a significant difference in the reduction of DBP in favor of dietary interventions: WMD, −3.41 mm Hg (95% CI, −5.55 to −1.27 mm Hg) (I2 = 36%) (Figure 2B).

Place holder to copy figure label and caption
Figure 2.

Diet vs usual care: changes in systolic blood pressure (A), diastolic blood pressure (B), and body weight (C). The size of the squares represents the weight of studies in meta-analysis (a numerical representation is given in the “Weight, %” column). The width of the diamond shapes represents the 95% CI (see also WMD [95% CI] column). A indicates atenolol; C, chlorthalidone; CG, control group; CI, confidence interval; DISH, Dietary Intervention Study of Hypertension; I2, Higgins I2; IG, intervention group; ODES, Oslo Diet and Exercise Study; P, placebo; Pa, physical activity; TAIM, Trial of Antihypertensive Interventions and Management; and WMD, weighted mean difference. *The SDs are calculated on the basis of P = .05. †The SDs are calculated on the basis of P = .001.

Graphic Jump Location

Of those investigations that could not be included in the meta-analyses, the study by Ruvolo et al25 found that a weight loss diet affected BP favorably, whereas in the study by Jalkanen,15 dietary interventions were less effective than usual care (Table 2). Two further studies1214,3848 reported not BP changes but the number of patients needing reinstatement of antihypertensive therapy after stopping all antihypertensive medication use at the beginning of the trials. In both studies, the number of patients eventually requiring antihypertensive therapy was lower in the diet groups.

Table Graphic Jump LocationTable 2. Characteristics and Results of Dietary Studies

Information on body weight change in hypertensive patients was available from 5 studies comparing diet with usual care (Table 2). A meta-analysis including 4 of these studies found a significant reduction in body weight of WMD −4.14 kg (95% CI, −4.98 to −3.30 kg) in patients in the diet groups compared with patients in the usual care groups (Figure 2C). Heterogeneity was I2 = 36%. The fifth study,25 not included in the meta-analysis owing to missing variables of variance, also showed a markedly higher reduction in body weight for patients treated by dietary means (Table 2).

PHARMACOLOGIC INTERVENTION STUDIES
Trial Characteristics and Quality

We identified 4 studies (Bakris et al,49 Cocco et al,50 Guy-Grand et al,51 and the XENDOS study810) that compared orlistat with placebo in 3132 hypertensive patients with a mean age of 46 to 55 years. Study duration ranged from 6 to 48 months. For sibutramine vs placebo, 4 studies (Fanghänel et al,52 Faria et al,53,54 and McMahon et al55,56) were identified. A total of 610 patients with a mean age of 46 to 53 years were included in these studies. Study duration ranged from 6 to 12 months. For results on study quality, see Table 1.

Results of Data Synthesis

None of the studies was designed to investigate the effects of therapy with orlistat or sibutramine on mortality or cardiovascular end points. It remains unclear whether therapy with orlistat or sibutramine will lead to beneficial or even disadvantageous outcomes. Gastrointestinal adverse effects were the adverse events most commonly reported by patients treated with orlistat. Formal statistical testing resulting in a significant difference in favor of placebo was presented in only 1 trial.49 In this study49 and in the XENDOS study,810 treatment with orlistat also resulted in a significantly higher proportion of patients experiencing musculoskeletal pain.

Whereas in the investigation by Fanghänel et al,52 patients in both comparison groups reported comparable rates of adverse events, Faria et al53,54 and McMahon et al55,56 found that more patients treated with sibutramine reported dry mouth as an adverse effect than did patients in the placebo group. In one of the studies by McMahon et al,55 the difference reached statistical significance. Faria et al53 also reported that arthralgia was more common with sibutramine treatment. Patients in the sibutramine groups experienced a higher rate of headaches than patients in the placebo groups.

All relevant studies investigating the effects of orlistat on BP could be included in meta-analyses (Table 3). For the XENDOS study,810 the results for the subgroup of patients with DBP of 90 mm Hg or greater at baseline after 12 months of study were used for the analysis. There was a significant reduction in SBP, with a WMD of −2.46 mm Hg (95% CI, −4.01 to −0.90 mm Hg) (I2 = 37%) in favor of orlistat (Figure 3A). Diastolic BP was also significantly reduced in patients treated with orlistat: WMD, −1.92 mm Hg (95% CI, −2.99 to −0.85 mm Hg) (I2 = 47%) (Figure 3B).

Place holder to copy figure label and caption
Figure 3.

Orlistat vs placebo: changes in systolic blood pressure (A), diastolic blood pressure (B), and body weight (C). The size of the squares represents the weight of studies in meta-analysis (a numerical representation is given in the “Weight, %” column). The width of the diamond shapes represents the 95% CI (see also WMD [95% CI] column). CG indicates control group; CI, confidence interval; I2, Higgins I2; IG, intervention group; D, diastolic blood pressure of 90 mm Hg or greater at baseline; WMD, weighted mean difference; and XENDOS, XENical in the prevention of Diabetes in Obese Subjects. *The SDs are calculated on the basis of P = .03. †The SDs are calculated on the basis of P = .01. ‡The SDs are calculated on the basis of P = .001.

Graphic Jump Location
Table Graphic Jump LocationTable 3. Characteristics and Results of Studies Investigating Orlistat

The 4 studies examining sibutramine vs placebo found disadvantageous BP effects for sibutramine (Table 4). A meta-analysis for SBP was not possible because, in all the studies, variability measurement data were missing. For the same reason, the results of the studies by Fanghänel et al52 and Faria et al53,54 could not be included in the meta-analysis on DBP. A combined analysis for DBP of the remaining 2 studies by McMahon et al55,56 showed a significant difference between sibutramine and placebo, with a detrimental effect in patients treated with sibutramine: WMD, 3.16 mm Hg (95% CI, 1.40 to 4.92 mm Hg) (I2 = 0%) (Figure 4A).

Place holder to copy figure label and caption
Figure 4.

Sibutramine vs placebo: changes in diastolic blood pressure (A) and body weight (B). The size of the squares represents the weight of studies in meta-analysis (a numerical representation is given in the “Weight, %” column). The width of the diamond shapes represents the 95% CI (see also WMD [95% CI] column). CI indicates confidence interval; I2, Higgins I2; and WMD, weighted mean difference. *The SDs are calculated on the basis of P = .004. †The SDs are calculated on the basis of P = .05.

Graphic Jump Location
Table Graphic Jump LocationTable 4. Characteristics and Results of Studies Investigating Sibutramine

Orlistat and sibutramine were found to lower body weight significantly more effectively than placebo in all the studies. The meta-analyses of orlistat studies obtained a WMD of −3.74 kg (95% CI, −4.70 to −2.78 kg) with I2 = 68% (Figure 3C). Differences in study quality could not explain heterogeneity. Also, no plausible explanation for heterogeneity could be deducted from differences in study design, study duration, sample sizes, interventions, or characteristics of included patients. For sibutramine trials, the WMD was −3.72 kg (95% CI, −4.85 to −2.59 kg), without heterogeneity (I2 = 3%) (Figure 4B). Of the 4 studies investigating sibutramine, 353,55,56 found that heart rate increased in patients treated with sibutramine and decreased or did not change in the control groups. Only 1 study52 showed lowering of heart rate in the intervention and control groups, with a more pronounced decrease in patients with sibutramine therapy.

This systematic review attempted to determine the long-term effects of weight loss through dietary, pharmacologic, or invasive interventions on patient-relevant end points, namely, death and cardiovascular complications, in the antihypertensive therapy of patients with essential hypertension but found that currently no randomized controlled trials designed to answer this question are available.

We found that dietary interventions to reduce body weight successfully reduced body weight and lowered BP in 1 year of follow-up in these patients. However, because all the studies except TAIM2637 and TONE3848 have major methodological deficiencies, the beneficial effects shown remain afflicted with some degree of uncertainty.

Of the 4 studies on the effects of orlistat included in the present analyses, only 1 was judged as having major deficiencies in study quality. The meta-analyses showed that patients being treated with orlistat could reduce their weight and BP levels significantly more than patients in the placebo groups. Although these results show that orlistat may be a helpful option in the antihypertensive therapy of obese hypertensive patients, some questions still remain. First, patients with orlistat therapy experienced adverse effects to a high degree, foremost of a gastrointestinal nature. This might unfavorably affect the effectiveness of the medication in settings outside of scientific studies. Furthermore, it remains unclear whether BP levels will remain low for a longer period or once the medication is discontinued because different investigations found body weight increasing again after 1 year, independent of whether orlistat treatment was continued.57,58

Although sibutramine reduced body weight about the same amount as orlistat, it did not show the same beneficial effects on BP. In 2 studies using a dosage of 20 mg/d, which is higher than the currently (in Germany) approved dosage of 10 to 15 mg/d, BP even rose in patients treated with sibutramine. This finding is further underlined by the results of a head-to-head comparison of orlistat vs sibutramine.59It found that, whereas in patients in the orlistat group (120 mg 3 times a day) a reduction of −8.4 kg of body weight resulted in a reduction in SBP and DBP of −4.0 and −3.0 mm Hg, respectively, the same loss of body weight of −8.3 kg in the sibutramine group did not cause a change in BP in patients treated with sibutramine, 10 mg/d (0.0 and 0.0 mm Hg). Also, in a meta-analysis by Kim et al60 comparing sibutramine with placebo in patients with or without hypertension at baseline, significant increases in SBP (1.6 mm Hg) and DBP (1.8 mm Hg) were found in the sibutramine treatment group despite a large effect on weight loss in this group.

Four studies (the RIO [Rimonabant in Obesity] studies)6164 investigated the effects of therapy with rimonabant, 20 and 5 mg/d, compared with placebo in study populations including normotensive and hypertensive (30%-60%) patients. None of these studies was designed to assess the effects on patient-relevant end points. Patients being treated with rimonabant, regardless of the dosage, reduced their body weight significantly more than placebo-treated patients. Contrary to these findings, the studies yielded heterogeneous results concerning BP changes. In particular, therapy with 5 mg of rimonabant showed inconsistent results, with a higher reduction in BP compared with placebo in some studies but less of a reduction in others. Treatment with 20 mg of rimonabant daily showed more uniform findings, with a higher reduction in SBP in all 4 studies (the difference was significant in 2). Also, the reduction in DBP was more pronounced in patients receiving rimonabant, 20 mg, than in placebo-treated patients in 3 studies (the difference was significant in 1), but slightly less in 1 study. Only the publication of the RIO Lipid study61 reported information on a hypertensive subgroup. In hypertensive patients treated with 20 mg of rimonabant, BP was reduced statistically significantly more than in patients in the placebo group (SBP: −5.9 mm Hg and DBP: −3.9 mm Hg). Because no other information on the hypertensive subgroup is given (the article does not even report the percentage of patients with hypertension at baseline), the relevance of these findings remains unclear. Hopefully, more results on hypertensive patients will be published.

A major limitation of this review is that because of the lack of information in the included studies, no conclusions on the effects of the different weight loss interventions on patient-relevant end points can be drawn. Also, because the maximum duration of the included trials was 4 years, and Sjöström et al65 found that BP in patients who successfully reduced their body weight by means of bariatric surgery was still reduced 2 years after surgery but increased again to baseline values after 10 years despite continued weight loss, the long-term effects of weight loss on BP found in this review are uncertain.

In conclusion, in patients with essential hypertension, therapy with dietary interventions to reduce body weight or with orlisat resulted in reductions in BP and body weight. A reduction in body weight of approximately 4 kg was necessary to achieve a reduction of approximately 6 mm Hg in SBP with dietary treatment and of approximately 2.5 mm Hg with orlistat. Although sibutramine treatment reduced body weight it did not lower or might even elevate BP. None of the studies provided data to answer the question whether risk of mortality or other patient-relevant end points can be lowered by weight reduction.

Correspondence: Karl Horvath, MD, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria (karl.horvath@meduni-graz.at).

Accepted for Publication: October 17, 2007.

Author Contributions: Drs Horvath, Jeitler, Siering, Stich, Skipka, Gratzer, and Siebenhofer had full access to all the data in the review; Dr Horvath takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Horvath, Jeitler, Siering, Stich, and Siebenhofer. Acquisition of data: Horvath, Jeitler, Siering, Stich, Gratzer, and Siebenhofer. Analysis and interpretation of data: Horvath, Jeitler, Siering, Stich, Skipka, and Siebenhofer. Drafting of the manuscript: Horvath. Critical revision of the manuscript for important intellectual content: Jeitler, Siering, Stich, Skipka, Gratzer, and Siebenhofer. Statistical analysis: Horvath, Skipka, and Siebenhofer. Administrative, technical, and material support: Siering and Stich. Study supervision: Horvath and Siebenhofer.

Financial Disclosure: None reported.

Previous Presentations: A report including part of the data presented in this study was published online in the German language and is available at the following Web site: http://www.iqwig.de/download/A05-21A_Abschlussbericht_Gewichtsreduktion_bei_Bluthochdruck..pdf. This study was presented in part as posters/oral presentation/abstracts at the 16th European Meeting on Hypertension, European Society of Hypertension; June 14, 2006; Madrid, Spain; the 11th Scientific Meeting of the EASD Hypertension in Diabetes Study Group, European Foundation for the Study of Diabetes; April 6, 2006; Belgrade, Serbia; and the 34th Jahrestagung der Österreichischen Diabetes Gesellschaft, Österreichische Diabetes Gesellschaft; November 17, 2006; Innsbruck, Austria.

Additional Information: This review was, for the most part, commissioned by and conducted in collaboration with the German Institute for Quality and Efficiency in Health Care.

 World Health Organization. The world health report 2003: shaping the future. http://www.who.int/entity/whr/2003/en/whr03_en.pdf. Accessed March 22, 2007
 World Health Organization. The world health report 2002: reducing risks, promoting healthy life. http://www.who.int/entity/whr/2002/en/whr02_en.pdf. Accessed March 22, 2007
Lewington  SClarke  RQizilbash  NPeto  RCollins  RProspective Studies Collaboration, Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies [published correction appears in Lancet. 2003;361(9362):1060]. Lancet 2002;360 (9349) 1903- 1913
PubMed
European Society of Hypertension-European Society of Cardiology Guidelines Committee, 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003;21 (6) 1011- 1053
PubMed
Chobanian  AVBakris  GLBlack  HR  et al.  The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003;289 (19) 2560- 2572
PubMed
Higgins  JPThompson  SGDeeks  JJAltman  DG Measuring inconsistency in meta-analyses. BMJ 2003;327 (7414) 557- 560
PubMed
Jackson  D The power of the standard test for the presence of heterogeneity in meta-analysis. Stat Med 2006;25 (15) 2688- 2699
PubMed
Institute for Quality and Efficiency in Health Care (IQWiG), Evaluation of the benefits and harms of non-drug treatment strategies in patients with essential hypertension: weight reduction. http://www.iqwig.de/download/A05-21A_Abschlussbericht_Gewichtsreduktion_bei_Bluthochdruck..pdf Accessed March 22, 2007>
Torgerson  JSArlinger  KKappi  MSjöström  L Principles for enhanced recruitment of subjects in a large clinical trial: the XENDOS (XENical in the prevention of Diabetes in Obese Subjects) study experience. Control Clin Trials 2001;22 (5) 515- 525
PubMed
Torgerson  JSHauptman  JBoldrin  MNSjöström  L XENical in the prevention of Diabetes in Obese Subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 2004;27 (1) 155- 161
PubMed
Croft  PRBrigg  DSmith  SHarrison  CBBranthwaite  ACollins  MF How useful is weight reduction in the management of hypertension? J R Coll Gen Pract 1986;36 (291) 445- 448
PubMed
Blaufox  MDLangford  HGOberman  AHawkins  CMWassertheil-Smoller  SWCutter  GR Effect of dietary change on the return of hypertension after withdrawal of prolonged antihypertensive therapy (DISH): Dietary Intervention Study of Hypertension. J Hypertens Suppl 1984;2 (3) S179- S181
PubMed
Langford  HGBlaufox  MDOberman  A  et al.  Return of hypertension after withdrawal of prolonged antihypertensive therapy, effect of weight loss, sodium reduction, and baseline factors. Trans Assoc Am Physicians 1984;97190- 196
PubMed
Langford  HGBlaufox  MDOberman  A  et al.  Dietary therapy slows the return of hypertension after stopping prolonged medication. JAMA 1985;253 (5) 657- 664
PubMed
Jalkanen  L The effect of a weight reduction program on cardiovascular risk factors among overweight hypertensives in primary health care. Scand J Soc Med 1991;19 (1) 66- 71
PubMed
 The Oslo Diet and Exercise Study (ODES): design and objectives. Control Clin Trials 1993;14 (3) 229- 243
PubMed
Anderssen  SHolme  IUrdal  PHjermann  I Diet and exercise intervention have favourable effects on blood pressure in mild hypertensives: the Oslo Diet and Exercise Study (ODES). Blood Press 1995;4 (6) 343- 349
PubMed
Anderssen  SAHjermann  IUrdal  PTorjesen  PAHolme  I Improved carbohydrate metabolism after physical training and dietary intervention in individuals with the “atherothrombogenic syndrome”: Oslo Diet and Exercise Study (ODES): a randomized trial. J Intern Med 1996;240 (4) 203- 209
PubMed
Anderssen  SAHaaland  AHjermann  IUrdal  PGjelsdal  KHolme  I Oslo Diet and Exercise Study: a one year randomized intervention trial: effect on haemostatic variables and other coronary risk factors. Nutr Metab Cardiovasc Dis 1995;5189- 200
Holme  IUrdal  PAnderssen  SHjermann  I Exercise-induced increase in lipoprotein (a). Atherosclerosis 1996;122 (1) 97- 104
PubMed
Reseland  JEAnderssen  SASolvoll  K  et al.  Effect of long-term changes in diet and exercise on plasma leptin concentrations. Am J Clin Nutr 2001;73 (2) 240- 245
PubMed
Sørensen  MAnderssen  SHjerman  IHolme  IUrsin  H Exercise and diet interventions improve perceptions of self in middle-aged adults. Scand J Med Sci Sports 1997;7 (5) 312- 320
PubMed
Sørensen  MAnderssen  SHjerman  IHolme  IUrsin  H The effect of exercise and diet on mental health and quality of life in middle-aged individuals with elevated risk factors for cardiovascular disease. J Sports Sci 1999;17 (5) 369- 377
PubMed
Torjesen  PABirkeland  KIAnderssen  SAHjermann  IHolme  IUrdal  P Lifestyle changes may reverse development of the insulin resistance syndrome: the Oslo Diet and Exercise Study: a randomized trial. Diabetes Care 1997;20 (1) 26- 31
PubMed
Ruvolo  GGreco  ESpeziale  GDi  NMMarino  B Effects of amlodipine and hypocaloric diet on the left ventricular mass in hypertensive obese patients [in Italian]. Minerva Cardioangiol 1994;42 (6) 289- 292
PubMed
Blaufox  MDLee  HBDavis  BOberman  AWassertheil-Smoller  SLangford  H Renin predicts diastolic blood pressure response to nonpharmacologic and pharmacologic therapy. JAMA 1992;267 (9) 1221- 1225
PubMed
Davis  BRBlaufox  MDHawkins  CM  et al.  Trial of antihypertensive interventions and management: design, methods, and selected baseline results. Control Clin Trials 1989;10 (1) 11- 30
PubMed
Davis  BROberman  ABlaufox  MD  et al. Trial of Antihypertensive Interventions and Management Research Group, Effect of antihypertensive therapy on weight loss. Hypertension 1992;19 (4) 393- 399
PubMed
Davis  BRBlaufox  MDOberman  A  et al.  Reduction in long-term antihypertensive medication requirements: effects of weight reduction by dietary intervention in overweight persons with mild hypertension. Arch Intern Med 1993;153 (15) 1773- 1782
PubMed
Davis  BROberman  ABlaufox  MD  et al.  Lack of effectiveness of a low-sodium/high-potassium diet in reducing antihypertensive medication requirements in overweight persons with mild hypertension: TAIM Research Group: Trial of Antihypertensive Interventions and Management. Am J Hypertens 1994;7 (10, pt 1) 926- 932
PubMed
Langford  HGDavis  BRBlaufox  D  et al. TAIM Research Group, Effect of drug and diet treatment of mild hypertension on diastolic blood pressure. Hypertension 1991;17 (2) 210- 217
PubMed
Oberman  AWassertheil-Smoller  SLangford  HG  et al.  Pharmacologic and nutritional treatment of mild hypertension: changes in cardiovascular risk status. Ann Intern Med 1990;112 (2) 89- 95
PubMed
Wassertheil-Smoller  SDavis  BROberman  A The TAIM Study: sex-race differences in effects of diet and drugs on cardiovascular risk. Cardiovascular Risk Factors 1991;1427- 435
Wassertheil-Smoller  SBlaufox  MDOberman  A  et al.  Effect of antihypertensives on sexual function and quality of life: the TAIM Study. Ann Intern Med 1991;114 (8) 613- 620
PubMed
Wassertheil-Smoller  SOberman  ABlaufox  MDDavis  BLangford  H The Trial of Antihypertensive Interventions and Management (TAIM) study: final results with regard to blood pressure, cardiovascular risk, and quality of life. Am J Hypertens 1992;5 (1) 37- 44
PubMed
Wassertheil-Smoller  SBlaufox  MDOberman  ASLangford  HGDavis  BRWylie-Rosett  J The Trial of Antihypertensive Interventions and Management (TAIM) study: adequate weight loss, alone and combined with drug therapy in the treatment of mild hypertension. Arch Intern Med 1992;152 (1) 131- 136
PubMed
Wylie-Rosett  JWassertheil-Smoller  SBlaufox  MD  et al.  Trial of antihypertensive intervention and management: greater efficacy with weight reduction than with a sodium-potassium intervention. J Am Diet Assoc 1993;93 (4) 408- 415
PubMed
Appel  LJEspeland  MWhelton  PK  et al.  Trial of Nonpharmacologic Interventions in the Elderly (TONE): design and rationale of a blood pressure control trial. Ann Epidemiol 1995;5 (2) 119- 129
PubMed
Appel  LJEspeland  MAEaster  LWilson  ACFolmar  SLacy  CR Effects of reduced sodium intake on hypertension control in older individuals: results from the Trial of Nonpharmacologic Interventions in the Elderly (TONE). Arch Intern Med 2001;161 (5) 685- 693
PubMed
Bahnson  JLWhelton  PKAppel  LJ  et al.  Baseline characteristics of randomized participants in the Trial of Nonpharmacologic Interventions in the Elderly (TONE). Dis Manage Clin Outcomes 1997;1 (2) 61- 68
Chao  DEspeland  MAFarmer  D  et al.  Effect of voluntary weight loss on bone mineral density in older overweight women. J Am Geriatr Soc 2000;48 (7) 753- 759
PubMed
Espeland  MAKumanyika  SKostis  JB  et al.  Antihypertensive medication use among recruits for the Trial of Nonpharmacologic Interventions in the Elderly (TONE). J Am Geriatr Soc 1996;44 (10) 1183- 1189
PubMed
Fessler  B Sodium reduction and weight loss instead of treatment with antihypertensive agents [in German]. Dtsch Apoth Ztg 1998;13836- 39
Kostis  JBEspeland  MAAppel  LJohnson  KCPierce  JWofford  JL Does withdrawal of antihypertensive medication increase the risk of cardiovascular events? Am J Cardiol 1998;82 (12) 1501- 1508
PubMed
Kostis  JBWilson  ACShindler  DMCosgrove  NMLacy  CR Persistence of normotension after discontinuation of lifestyle intervention in the trial of TONE. Am J Hypertens 2002;15 (8) 732- 734
PubMed
Kumanyika  SKEspeland  MABahnson  JL  et al.  Ethnic comparison of weight loss in the Trial of Nonpharmacologic Interventions in the Elderly. Obes Res 2002;10 (2) 96- 106
PubMed
Whelton  PKBabnson  JAppel  LJ  et al.  Recruitment in the Trial of Nonpharmacologic Interventions in the Elderly (TONE). J Am Geriatr Soc 1997;45 (2) 185- 193
PubMed
Whelton  PKAppel  LJEspeland  MA  et al.  Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled Trial of Nonpharmacologic Interventions in the Elderly (TONE). JAMA 1998;279 (11) 839- 846
PubMed
Bakris  GCalhoun  DEgan  B  et al.  Orlistat improves blood pressure control in obese subjects with treated but inadequately controlled hypertension. J Hypertens 2002;20 (11) 2257- 2267
PubMed
Cocco  GPandolfi  SRousson  V Sufficient weight reduction decreases cardiovascular complications in diabetic patients with the metabolic syndrome: a randomized study of orlistat as an adjunct to lifestyle changes (diet and exercise). Heart Drug 2005;568- 74
Guy-Grand  BDrouin  PEschwege  EGin  HJoubert  JMValensi  P Effects of orlistat on obesity-related diseases: a six-month randomized trial. Diabetes Obes Metab 2004;6 (5) 375- 383
PubMed
Fanghänel  GCortinas  LSanchez-Reyes  LGomez-Santos  RCampos-Franco  EBerber  A Safety and efficacy of sibutramine in overweight Hispanic patients with hypertension. Adv Ther 2003;20 (2) 101- 113
PubMed
Faria  ANRibeiro Filho  FFLerario  DDKohlmann  NFerreira  SRZanella  MT Effects of sibutramine on the treatment of obesity in patients with arterial hypertension. Arq Bras Cardiol 2002;78 (2) 172- 180
PubMed
Faria  ANRibeiro Filho  FFKohlmann  NEGouvea  F  SrZanella  MT Effects of sibutramine on abdominal fat mass, insulin resistance and blood pressure in obese hypertensive patients. Diabetes Obes Metab 2005;7 (3) 246- 253
PubMed
McMahon  FGFujioka  KSingh  BN  et al.  Efficacy and safety of sibutramine in obese white and African American patients with hypertension: a 1-year, double-blind, placebo-controlled, multicenter trial. Arch Intern Med 2000;160 (14) 2185- 2191
PubMed
McMahon  FGWeinstein  SPRowe  E  et al.  Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors. J Hum Hypertens 2002;16 (1) 5- 11
PubMed
Davidson  MHHauptman  JDiGirolamo  M  et al.  Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial [published correction appears in JAMA. 1999;281(13):1174]. JAMA 1999;281 (3) 235- 242
PubMed
Sjöström  LRissanen  AAndersen  T  et al. European Multicentre Orlistat Study Group, Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. Lancet 1998;352 (9123) 167- 172
PubMed
Derosa  GCicero  AFMurdolo  G  et al.  Efficacy and safety comparative evaluation of orlistat and sibutramine treatment in hypertensive obese patients. Diabetes Obes Metab 2005;7 (1) 47- 55
PubMed
Kim  SHLee  YMJee  SHNam  CM Effect of sibutramine on weight loss and blood pressure: a meta-analysis of controlled trials. Obes Res 2003;11 (9) 1116- 1123
PubMed
Després  J-PGolay  ASjöström  L Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 2005;353 (20) 2121- 2134
PubMed
Pi-Sunyer  FXAronne  LJHeshmati  HMDevin  JRosenstock  JRIO-North America Study Group, Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial [published correction appears in JAMA. 2006;295(11):1252]. JAMA 2006;295 (7) 761- 775
PubMed
Scheen  AJFiner  NHollander  PJensen  MDVan Gaal  LF Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet 2006;368 (9548) 1660- 1672
PubMed
Van Gaal  LFRissanen  AMScheen  AJZiegler  ORossner  SRIO-Europe Study Group, Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study [published correction appears in Lancet. 2005;366(9483):370]. Lancet 2005;365 (9468) 1389- 1397
PubMed
Sjöström  LLindroos  AKPeltonen  M  et al.  Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 2004;351 (26) 2683- 2693
PubMed

Figures

Place holder to copy figure label and caption
Figure 1.

Flow diagram of the systematic review. EMEA indicates European Agency for the Evaluation of Medicinal Products; FDA, Food and Drug Administration; and RCT, randomized controlled trial.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Diet vs usual care: changes in systolic blood pressure (A), diastolic blood pressure (B), and body weight (C). The size of the squares represents the weight of studies in meta-analysis (a numerical representation is given in the “Weight, %” column). The width of the diamond shapes represents the 95% CI (see also WMD [95% CI] column). A indicates atenolol; C, chlorthalidone; CG, control group; CI, confidence interval; DISH, Dietary Intervention Study of Hypertension; I2, Higgins I2; IG, intervention group; ODES, Oslo Diet and Exercise Study; P, placebo; Pa, physical activity; TAIM, Trial of Antihypertensive Interventions and Management; and WMD, weighted mean difference. *The SDs are calculated on the basis of P = .05. †The SDs are calculated on the basis of P = .001.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Orlistat vs placebo: changes in systolic blood pressure (A), diastolic blood pressure (B), and body weight (C). The size of the squares represents the weight of studies in meta-analysis (a numerical representation is given in the “Weight, %” column). The width of the diamond shapes represents the 95% CI (see also WMD [95% CI] column). CG indicates control group; CI, confidence interval; I2, Higgins I2; IG, intervention group; D, diastolic blood pressure of 90 mm Hg or greater at baseline; WMD, weighted mean difference; and XENDOS, XENical in the prevention of Diabetes in Obese Subjects. *The SDs are calculated on the basis of P = .03. †The SDs are calculated on the basis of P = .01. ‡The SDs are calculated on the basis of P = .001.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.

Sibutramine vs placebo: changes in diastolic blood pressure (A) and body weight (B). The size of the squares represents the weight of studies in meta-analysis (a numerical representation is given in the “Weight, %” column). The width of the diamond shapes represents the 95% CI (see also WMD [95% CI] column). CI indicates confidence interval; I2, Higgins I2; and WMD, weighted mean difference. *The SDs are calculated on the basis of P = .004. †The SDs are calculated on the basis of P = .05.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 2. Characteristics and Results of Dietary Studies
Table Graphic Jump LocationTable 3. Characteristics and Results of Studies Investigating Orlistat
Table Graphic Jump LocationTable 4. Characteristics and Results of Studies Investigating Sibutramine

References

 World Health Organization. The world health report 2003: shaping the future. http://www.who.int/entity/whr/2003/en/whr03_en.pdf. Accessed March 22, 2007
 World Health Organization. The world health report 2002: reducing risks, promoting healthy life. http://www.who.int/entity/whr/2002/en/whr02_en.pdf. Accessed March 22, 2007
Lewington  SClarke  RQizilbash  NPeto  RCollins  RProspective Studies Collaboration, Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies [published correction appears in Lancet. 2003;361(9362):1060]. Lancet 2002;360 (9349) 1903- 1913
PubMed
European Society of Hypertension-European Society of Cardiology Guidelines Committee, 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003;21 (6) 1011- 1053
PubMed
Chobanian  AVBakris  GLBlack  HR  et al.  The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003;289 (19) 2560- 2572
PubMed
Higgins  JPThompson  SGDeeks  JJAltman  DG Measuring inconsistency in meta-analyses. BMJ 2003;327 (7414) 557- 560
PubMed
Jackson  D The power of the standard test for the presence of heterogeneity in meta-analysis. Stat Med 2006;25 (15) 2688- 2699
PubMed
Institute for Quality and Efficiency in Health Care (IQWiG), Evaluation of the benefits and harms of non-drug treatment strategies in patients with essential hypertension: weight reduction. http://www.iqwig.de/download/A05-21A_Abschlussbericht_Gewichtsreduktion_bei_Bluthochdruck..pdf Accessed March 22, 2007>
Torgerson  JSArlinger  KKappi  MSjöström  L Principles for enhanced recruitment of subjects in a large clinical trial: the XENDOS (XENical in the prevention of Diabetes in Obese Subjects) study experience. Control Clin Trials 2001;22 (5) 515- 525
PubMed
Torgerson  JSHauptman  JBoldrin  MNSjöström  L XENical in the prevention of Diabetes in Obese Subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 2004;27 (1) 155- 161
PubMed
Croft  PRBrigg  DSmith  SHarrison  CBBranthwaite  ACollins  MF How useful is weight reduction in the management of hypertension? J R Coll Gen Pract 1986;36 (291) 445- 448
PubMed
Blaufox  MDLangford  HGOberman  AHawkins  CMWassertheil-Smoller  SWCutter  GR Effect of dietary change on the return of hypertension after withdrawal of prolonged antihypertensive therapy (DISH): Dietary Intervention Study of Hypertension. J Hypertens Suppl 1984;2 (3) S179- S181
PubMed
Langford  HGBlaufox  MDOberman  A  et al.  Return of hypertension after withdrawal of prolonged antihypertensive therapy, effect of weight loss, sodium reduction, and baseline factors. Trans Assoc Am Physicians 1984;97190- 196
PubMed
Langford  HGBlaufox  MDOberman  A  et al.  Dietary therapy slows the return of hypertension after stopping prolonged medication. JAMA 1985;253 (5) 657- 664
PubMed
Jalkanen  L The effect of a weight reduction program on cardiovascular risk factors among overweight hypertensives in primary health care. Scand J Soc Med 1991;19 (1) 66- 71
PubMed
 The Oslo Diet and Exercise Study (ODES): design and objectives. Control Clin Trials 1993;14 (3) 229- 243
PubMed
Anderssen  SHolme  IUrdal  PHjermann  I Diet and exercise intervention have favourable effects on blood pressure in mild hypertensives: the Oslo Diet and Exercise Study (ODES). Blood Press 1995;4 (6) 343- 349
PubMed
Anderssen  SAHjermann  IUrdal  PTorjesen  PAHolme  I Improved carbohydrate metabolism after physical training and dietary intervention in individuals with the “atherothrombogenic syndrome”: Oslo Diet and Exercise Study (ODES): a randomized trial. J Intern Med 1996;240 (4) 203- 209
PubMed
Anderssen  SAHaaland  AHjermann  IUrdal  PGjelsdal  KHolme  I Oslo Diet and Exercise Study: a one year randomized intervention trial: effect on haemostatic variables and other coronary risk factors. Nutr Metab Cardiovasc Dis 1995;5189- 200
Holme  IUrdal  PAnderssen  SHjermann  I Exercise-induced increase in lipoprotein (a). Atherosclerosis 1996;122 (1) 97- 104
PubMed
Reseland  JEAnderssen  SASolvoll  K  et al.  Effect of long-term changes in diet and exercise on plasma leptin concentrations. Am J Clin Nutr 2001;73 (2) 240- 245
PubMed
Sørensen  MAnderssen  SHjerman  IHolme  IUrsin  H Exercise and diet interventions improve perceptions of self in middle-aged adults. Scand J Med Sci Sports 1997;7 (5) 312- 320
PubMed
Sørensen  MAnderssen  SHjerman  IHolme  IUrsin  H The effect of exercise and diet on mental health and quality of life in middle-aged individuals with elevated risk factors for cardiovascular disease. J Sports Sci 1999;17 (5) 369- 377
PubMed
Torjesen  PABirkeland  KIAnderssen  SAHjermann  IHolme  IUrdal  P Lifestyle changes may reverse development of the insulin resistance syndrome: the Oslo Diet and Exercise Study: a randomized trial. Diabetes Care 1997;20 (1) 26- 31
PubMed
Ruvolo  GGreco  ESpeziale  GDi  NMMarino  B Effects of amlodipine and hypocaloric diet on the left ventricular mass in hypertensive obese patients [in Italian]. Minerva Cardioangiol 1994;42 (6) 289- 292
PubMed
Blaufox  MDLee  HBDavis  BOberman  AWassertheil-Smoller  SLangford  H Renin predicts diastolic blood pressure response to nonpharmacologic and pharmacologic therapy. JAMA 1992;267 (9) 1221- 1225
PubMed
Davis  BRBlaufox  MDHawkins  CM  et al.  Trial of antihypertensive interventions and management: design, methods, and selected baseline results. Control Clin Trials 1989;10 (1) 11- 30
PubMed
Davis  BROberman  ABlaufox  MD  et al. Trial of Antihypertensive Interventions and Management Research Group, Effect of antihypertensive therapy on weight loss. Hypertension 1992;19 (4) 393- 399
PubMed
Davis  BRBlaufox  MDOberman  A  et al.  Reduction in long-term antihypertensive medication requirements: effects of weight reduction by dietary intervention in overweight persons with mild hypertension. Arch Intern Med 1993;153 (15) 1773- 1782
PubMed
Davis  BROberman  ABlaufox  MD  et al.  Lack of effectiveness of a low-sodium/high-potassium diet in reducing antihypertensive medication requirements in overweight persons with mild hypertension: TAIM Research Group: Trial of Antihypertensive Interventions and Management. Am J Hypertens 1994;7 (10, pt 1) 926- 932
PubMed
Langford  HGDavis  BRBlaufox  D  et al. TAIM Research Group, Effect of drug and diet treatment of mild hypertension on diastolic blood pressure. Hypertension 1991;17 (2) 210- 217
PubMed
Oberman  AWassertheil-Smoller  SLangford  HG  et al.  Pharmacologic and nutritional treatment of mild hypertension: changes in cardiovascular risk status. Ann Intern Med 1990;112 (2) 89- 95
PubMed
Wassertheil-Smoller  SDavis  BROberman  A The TAIM Study: sex-race differences in effects of diet and drugs on cardiovascular risk. Cardiovascular Risk Factors 1991;1427- 435
Wassertheil-Smoller  SBlaufox  MDOberman  A  et al.  Effect of antihypertensives on sexual function and quality of life: the TAIM Study. Ann Intern Med 1991;114 (8) 613- 620
PubMed
Wassertheil-Smoller  SOberman  ABlaufox  MDDavis  BLangford  H The Trial of Antihypertensive Interventions and Management (TAIM) study: final results with regard to blood pressure, cardiovascular risk, and quality of life. Am J Hypertens 1992;5 (1) 37- 44
PubMed
Wassertheil-Smoller  SBlaufox  MDOberman  ASLangford  HGDavis  BRWylie-Rosett  J The Trial of Antihypertensive Interventions and Management (TAIM) study: adequate weight loss, alone and combined with drug therapy in the treatment of mild hypertension. Arch Intern Med 1992;152 (1) 131- 136
PubMed
Wylie-Rosett  JWassertheil-Smoller  SBlaufox  MD  et al.  Trial of antihypertensive intervention and management: greater efficacy with weight reduction than with a sodium-potassium intervention. J Am Diet Assoc 1993;93 (4) 408- 415
PubMed
Appel  LJEspeland  MWhelton  PK  et al.  Trial of Nonpharmacologic Interventions in the Elderly (TONE): design and rationale of a blood pressure control trial. Ann Epidemiol 1995;5 (2) 119- 129
PubMed
Appel  LJEspeland  MAEaster  LWilson  ACFolmar  SLacy  CR Effects of reduced sodium intake on hypertension control in older individuals: results from the Trial of Nonpharmacologic Interventions in the Elderly (TONE). Arch Intern Med 2001;161 (5) 685- 693
PubMed
Bahnson  JLWhelton  PKAppel  LJ  et al.  Baseline characteristics of randomized participants in the Trial of Nonpharmacologic Interventions in the Elderly (TONE). Dis Manage Clin Outcomes 1997;1 (2) 61- 68
Chao  DEspeland  MAFarmer  D  et al.  Effect of voluntary weight loss on bone mineral density in older overweight women. J Am Geriatr Soc 2000;48 (7) 753- 759
PubMed
Espeland  MAKumanyika  SKostis  JB  et al.  Antihypertensive medication use among recruits for the Trial of Nonpharmacologic Interventions in the Elderly (TONE). J Am Geriatr Soc 1996;44 (10) 1183- 1189
PubMed
Fessler  B Sodium reduction and weight loss instead of treatment with antihypertensive agents [in German]. Dtsch Apoth Ztg 1998;13836- 39
Kostis  JBEspeland  MAAppel  LJohnson  KCPierce  JWofford  JL Does withdrawal of antihypertensive medication increase the risk of cardiovascular events? Am J Cardiol 1998;82 (12) 1501- 1508
PubMed
Kostis  JBWilson  ACShindler  DMCosgrove  NMLacy  CR Persistence of normotension after discontinuation of lifestyle intervention in the trial of TONE. Am J Hypertens 2002;15 (8) 732- 734
PubMed
Kumanyika  SKEspeland  MABahnson  JL  et al.  Ethnic comparison of weight loss in the Trial of Nonpharmacologic Interventions in the Elderly. Obes Res 2002;10 (2) 96- 106
PubMed
Whelton  PKBabnson  JAppel  LJ  et al.  Recruitment in the Trial of Nonpharmacologic Interventions in the Elderly (TONE). J Am Geriatr Soc 1997;45 (2) 185- 193
PubMed
Whelton  PKAppel  LJEspeland  MA  et al.  Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled Trial of Nonpharmacologic Interventions in the Elderly (TONE). JAMA 1998;279 (11) 839- 846
PubMed
Bakris  GCalhoun  DEgan  B  et al.  Orlistat improves blood pressure control in obese subjects with treated but inadequately controlled hypertension. J Hypertens 2002;20 (11) 2257- 2267
PubMed
Cocco  GPandolfi  SRousson  V Sufficient weight reduction decreases cardiovascular complications in diabetic patients with the metabolic syndrome: a randomized study of orlistat as an adjunct to lifestyle changes (diet and exercise). Heart Drug 2005;568- 74
Guy-Grand  BDrouin  PEschwege  EGin  HJoubert  JMValensi  P Effects of orlistat on obesity-related diseases: a six-month randomized trial. Diabetes Obes Metab 2004;6 (5) 375- 383
PubMed
Fanghänel  GCortinas  LSanchez-Reyes  LGomez-Santos  RCampos-Franco  EBerber  A Safety and efficacy of sibutramine in overweight Hispanic patients with hypertension. Adv Ther 2003;20 (2) 101- 113
PubMed
Faria  ANRibeiro Filho  FFLerario  DDKohlmann  NFerreira  SRZanella  MT Effects of sibutramine on the treatment of obesity in patients with arterial hypertension. Arq Bras Cardiol 2002;78 (2) 172- 180
PubMed
Faria  ANRibeiro Filho  FFKohlmann  NEGouvea  F  SrZanella  MT Effects of sibutramine on abdominal fat mass, insulin resistance and blood pressure in obese hypertensive patients. Diabetes Obes Metab 2005;7 (3) 246- 253
PubMed
McMahon  FGFujioka  KSingh  BN  et al.  Efficacy and safety of sibutramine in obese white and African American patients with hypertension: a 1-year, double-blind, placebo-controlled, multicenter trial. Arch Intern Med 2000;160 (14) 2185- 2191
PubMed
McMahon  FGWeinstein  SPRowe  E  et al.  Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors. J Hum Hypertens 2002;16 (1) 5- 11
PubMed
Davidson  MHHauptman  JDiGirolamo  M  et al.  Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial [published correction appears in JAMA. 1999;281(13):1174]. JAMA 1999;281 (3) 235- 242
PubMed
Sjöström  LRissanen  AAndersen  T  et al. European Multicentre Orlistat Study Group, Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. Lancet 1998;352 (9123) 167- 172
PubMed
Derosa  GCicero  AFMurdolo  G  et al.  Efficacy and safety comparative evaluation of orlistat and sibutramine treatment in hypertensive obese patients. Diabetes Obes Metab 2005;7 (1) 47- 55
PubMed
Kim  SHLee  YMJee  SHNam  CM Effect of sibutramine on weight loss and blood pressure: a meta-analysis of controlled trials. Obes Res 2003;11 (9) 1116- 1123
PubMed
Després  J-PGolay  ASjöström  L Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 2005;353 (20) 2121- 2134
PubMed
Pi-Sunyer  FXAronne  LJHeshmati  HMDevin  JRosenstock  JRIO-North America Study Group, Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial [published correction appears in JAMA. 2006;295(11):1252]. JAMA 2006;295 (7) 761- 775
PubMed
Scheen  AJFiner  NHollander  PJensen  MDVan Gaal  LF Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet 2006;368 (9548) 1660- 1672
PubMed
Van Gaal  LFRissanen  AMScheen  AJZiegler  ORossner  SRIO-Europe Study Group, Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study [published correction appears in Lancet. 2005;366(9483):370]. Lancet 2005;365 (9468) 1389- 1397
PubMed
Sjöström  LLindroos  AKPeltonen  M  et al.  Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 2004;351 (26) 2683- 2693
PubMed

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 41

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Topics
PubMed Articles
Food ingredients as anti-obesity agents: a review. Crit Rev Food Sci Nutr 2013;53(9):929-42.
Obesity drug therapy. Minerva Endocrinol 2013;38(3):245-54.
JAMAevidence.com

Users' Guides to the Medical Literature
Clinical Scenario

Users' Guides to the Medical Literature
Example 1: Diabetes and Target Blood Pressure