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STATE OF THE ART nature publishing group

Obesity-Related Hypertension: Epidemiology,
Pathophysiology, and Clinical Management
Theodore A. Kotchen1

The prevalence of obesity, including childhood obesity, is increasing treatment of the obese hypertensive patient should address overall
worldwide. Weight gain is associated with increases in arterial cardiovascular disease (CVD) risk. There are no compelling clinical
pressure, and it has been estimated that 60–70% of hypertension trial data to indicate that any one class of antihypertensive agents is
in adults is attributable to adiposity. Centrally located body fat, superior to others, and in general the principles of pharmacotherapy
associated with insulin resistance and dyslipidemia, is a more potent for obese hypertensive patients are not different from nonobese
determinant of blood pressure elevation than peripheral body patients. Future research directions might include: (i) development
fat. Obesity-related hypertension may be a distinct hypertensive of effective, culturally sensitive strategies for the prevention and
phenotype with distinct genetic determinants. Mechanisms of treatment of obesity; (ii) clinical trials to identify the most effective
obesity-related hypertension include insulin resistance, sodium drug therapies for reducing CVD in obese, hypertensive patients;
retention, increased sympathetic nervous system activity, activation (iii) continued search for the genetic determinants of the obese,
of renin–angiotensin–aldosterone, and altered vascular function. In hypertensive phenotype.
overweight individuals, weight loss results in a reduction of blood
pressure, however, this effect may be attenuated in the long term. Keywords: adipokines; blood pressure; central obesity; hypertension;
An increasing number of community-based programs (including insulin resistance
school programs and worksite programs) are being developed
for the prevention and treatment of obesity. Assessment and American Journal of Hypertension, advance online publication 12 August 2010;

Obesity is associated with increased morbidity and ­mortality and socioeconomic groups. Approximately 68% of US adults
due to hypertension, diabetes, dyslipidemia, and cardiovas- are either overweight or obese.6 Based on National Health
cular and renal diseases.1–3 The prevalence of obesity and and Nutrition Examination Survey data, the prevalence of
­obesity-related disease is increasing worldwide. The Centers obesity in 2007–2008 was 32.2% among adult men and 35.5%
for Disease Control and Prevention estimated that obesity cost among adult women.5 Among adults, the prevalence of obesity
the United States at least $147 billion in 2008. Consequently, increases with age in men. The prevalence of obesity among
strategies for preventing and treating obesity have become African Americans is ~1.5 times that in whites, and Mexican
political as well as health-care issues. Americans have an intermediate prevalence.4
Scientific and medical interest in the relationship between During the past three decades, prevalence rates of child-
obesity and hypertension is reflected in the number of publi- hood and adolescent obesity (body mass index (BMI) >95th
cations related to this topic. The number of English language percentile for age and sex) have more than doubled in the
citations in PubMed for “obesity AND hypertension” progres- United States.7 In 2006, 16.3% of children and adolescents were
sively increased from 203 in 1990 to 1,427 in 2009, with most reportedly obese,8 and ~32% of children are either overweight
of the increase occurring in the past decade. The purpose of or obese.6 Childhood obesity frequently persists into adult-
this report is to review information about the epidemiology, hood, with up to 80% of obese children reported to become
pathogenic mechanisms, and strategies for prevention and obese adults.9 Among adolescents, the prevalence of obesity
treatment of obesity-related hypertension. is approximately twice as high among African Americans and
Mexican Americans than among non-Hispanic whites.7
Epidemiology of Obesity and Hypertension Because of the increasing prevalence of obesity in the United
In both adults and children, obesity rates have increased over States, it has been projected that the steady increase in life
the past several decades in the United States.4,5 Obesity rates expectancy during the past two centuries will soon end.10
have increased in both genders, and among all racial, ethnic, However, recent reports from the Centers for Disease Control
and Prevention suggest that obesity rates may be stabilizing.5,11
1Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, Obesity rates have remained constant for 5 years in men and
USA. Correspondence: Theodore A. Kotchen ( closer to 10 years in women and children.
Received 6 June 2010; first decision 26 June 2010; accepted 12 July 2010. The prevalence of obesity is increasing not only in the United
© 2010 American Journal of Hypertension, Ltd. States, but also globally.12,13 Socioeconomic and ­demographic

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100 107 1. It has been esti- nomic status groups.26. diet.397 1. mortality from ischemic were greatest among young adults (Table 2).htm and www.27 Additionally.2 28.19. AMERICAN JOURNAL OF HYPERTENSION | VOLUME 23 NUMBER 11 | november 2010 1171 .and pressures in children have increased in the past decade. Hypertension = systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg. Table 2 | Age-specific prevalence of hypertension and obesity in the United States at two time periods.16 The increasing prevalence of prevalence of obesity.9 34. Similar to adults.26 Blood countries (Table  1).14 Obesity ent among hypertensive individuals than among the general rates have increased threefold or more since 1980 in the Middle population. Obesity = body mass index >30 kg/m2.12 prevalence of overweight. the preva- In parallel with increasing obesity rates.19 Possibly related to the increased national product increases.297 1. and China.0 to 28. longitudinal Table 1 | Global mortality estimates (in thousands) due ischemic heart disease and cerebrovascular disease.15 Obesity in fold increased likelihood of having hypertension. of hypertensive adults are >20% overweight.18–21 even among lean individuals. the Pacific Islands.8 14 23. low. or taking antihypertensive medication. the prevalence of obesity in the developing world had ation of indices of adiposity with blood pressure is less appar- increased from 2.Obesity-Related Hypertension STATE OF THE ART transitions occurring in many developing countries are Cross-sectional and longitudinal studies document an ­contributing to the escalation of obesity despite continuing a­ ssociation of blood pressure with body weight and an asso- nutritional deficiencies.5 27 >60 57. at least in part. in US adults the prevalence of hyper- obesity is related to urbanization.24) 60% the developing world is no longer a disease of higher socioeco. the associ- 1998.5- almost all countries for which data are available. Australasia. to an increased annual global mortality of 25 million due to CVD.737 3.17 Between 1990 and 2020. the prevalence of hypertension is threefold siderably greater extent in developing than in ­developed higher in obese children than in nonobese children.454 3.3 to 19.4 45 17. by sex.260 124   Developed countries 867 1.9 65.7 67 40–59 27.12.14 1999–2000. Additionally.921 48 Cerebrovascular Disease   Developing countries 1. It is projected that by 2020.23 suggesting that the blood pressure–adiposity East.0 35. and ­middle-income countries will contribute 19 million of the this may also be attributable.113 28 539 841 56 Adapted from reference 17. relationship in hypertensives is modulated by environmental the prevalence of childhood overweight has increased in and genetic factors. and percent increase over time Hypertension prevalence (%) Obesity prevalence (%) Age (years) 1988–1991 2005–2006 Percent increase 1988–1994 2005–2008 Percent increase 18–39 5.0 42 Based on National Health and Nutrition Examination Survey data obtained from reference 25 and the following Centers for Disease Control and Prevention web sites: www.825 120 1.25 Between 1988–1994 and 2007–2008. and a reduction in physical activity. cardiovascular lence of both obesity and hypertension increased among all ­disease (CVD) mortality is rapidly increasing in developing age groups of adults. Nevertheless.1 19 28. the burden of obesity is shifting toward mated that 60–70% of hypertension in adults may be directly groups with lower socioeconomic status as the country’s gross ­attributable to adiposity.809 29 1. This double burden poses health and ciation of blood pressure increases over time with weight economic challenges in resource-constrained populations.cdc.7% between 1988–1991 and supply.337 137   Developed countries 1. In 4. between 1990 and 2020 Women Men 1990 2020 % Increase 1990 2020 % Increase Ischemic heart disease   Developing countries 1.499 3. although percentage increases of both countries. heart disease and cerebrovascular disease increased to a con.0 nchs/nhanes/nhanes2007-2008/nhanes07_08.1 7.6% over a 10-year period. obese individuals have a 3.cdc. major changes in the food tension increased from 25.22 However.

35.37 In African with significant logarithm (base 10) of odds scores on chro- Americans. and approaches 50% in severely obese youngsters. insulin resistance.. An understanding of information than the individual risk factors by themselves has the mechanisms of obesity-related hypertension may have been questioned. which Impaired vascular endothelial function Insulin resistance may represent the initiation or early phase in the evolution of Other vascular mechanisms Insulin resistance atherosclerosis. and the timing of onset of childhood Renin–angiotensin obesity. Environmental factors include alcohol Increased SNS activity Insulin resistance intake. as measured by hypertension in overweight and obese individuals. For example.29 Increased cortisol activity Visceral obesity or “android” obesity is in part hormonally determined.36 Impaired vasoreactivity. Depending on populations studied and methods of measure- related hypertension may represent a genetically ­distinct ment. but not ­leptin.STATE OF THE ART Obesity-Related Hypertension s­ tudies document that weight gain is associated with increases Table 3 | Putative mechanisms of obesity-related hypertension in blood pressure and hypertension incidence.44 In a relatively isolated French Canadian population. diastolic blood pressure. particularly sympathetic with adiposity may also contribute to the development of activity to the kidney and skeletal muscle. For example. Possible underlying in the Framingham Heart Study. and to common forms of obesity has recently been reviewed.g.43 interdependent. Further.45 Nevertheless. manifested by ­endothelium-dependent coronary and peripheral vasodilation.38 In children and adolescents. more closely related to abdominal visceral fat than to total fat 1172 november 2010 | VOLUME 23 NUMBER 11 | AMERICAN JOURNAL OF HYPERTENSION . a total genome syndrome may be heritable. but as shown in the rodent.g. with blood pressure levels and hypertension in men. lence of the metabolic syndrome increases with the severity of obesity.39 Pathophysiology of Obesity-Related Hypertension Although the metabolic syndrome is associated with increased Environmental (e. “stress”). is more strongly correlated with abdominal Altered vascular ion transport obesity than with BMI. Primary mechanisms mechanisms ciated with a 20–30% increase in hypertension incidence.” This early onset hypertension and/or dyslipidemia. it may scan identified a cluster of overlapping quantitative trait loci be induced by diets high in simple carbohydrates. and G-protein β3 graphy. heritabilities of hypertension and/or obesity. Anatomic renal compression tal and genetic factors. Most genes that have been found to contribute to the patho- genesis of obesity are expressed in the brain and appear to Sympathetic nervous system exert their effects by modulation of feeding behavior. the preva. and low levels of high-density lipo. specific in women. sympathetic nervous system. β3-adrenergic receptor. fasting insulin. respectively. in 120 extended families with at least one sib pair affected with protein cholesterol constitutes the “metabolic syndrome. possibly reflecting the difference between android genetic factors have not been identified to account for the high and gynecoid obesity. tumor regional norepinephrine kinetic studies and microneuro­ necrosis factor-α.28. some genes associated tem activity is increased in obesity. level of risk of all cause and cardiovascular morbidity and content. physiological.36 SNS. to date.40–42 important therapeutic implications. most evidence indicate that sympathetic nervous sys- hypertensive phenotype. and genetic factors influence the whether the designation of a syndrome provides more risk impact of obesity on arterial pressure. insulin resist- Increased circulating renin–angiotensin Increased renal SNS activity ance and obesity are associated with vascular endothelial dys- Increased adipose renin–angiotensin function. cigarette smoking. The putative physiologic Evidence for a genetic contribution to both rare monogenic mechanisms of obesity-related hypertension are complex.46–48 Neural activity to skeletal muscle is subunit. hypertension.34 Visceral obesity also increases the risks Psychological stress for insulin resistance and dyslipidemia. Obesity. and redundant (Table 3). Sodium retention Antinatriuretic effect of insulin and the Harvard Male Alumni study found a weight gain of Increased renal SNS activity 25 pounds was associated with a 60% increase in hypertension Increased aldosterone incidence. high serum triglyceride concentrations. we have found that insulin resistance is associated mosome 1 for the following phenotypes: BMI. The constellation of centripetal obesity (measured as waist circumference). Body fat distribution is also affected by environmen. physical activity.30 Most studies suggest that centrally located body fat is Leptin/other adipokines a more important determinant of blood pressure elevation than Obstructive sleep apnea peripheral body fat in both men and women.31–33 The relation- β Adrenergic receptor ship between waist–hip ratio and blood pressure appears to be polymorphisms independent of BMI. e. a 5% weight gain was asso.

Among African Americans. insulin resist- centrations are relatively high in African Americans with the ance. pharmacologic blockade with Obesity-related hypertension is associated with renal sodium ­angiotensin-converting enzymes (ACEs) or angiotensin II retention and impaired pressure natriuresis.50 nounced in visceral than in subcutaneous adipose tissue.49.47 However.53. This conversion is more pro- lence of obesity. waist circumference. leptin or other adipokines. muscle sympathetic dehydrogenase type 1 activates cortisone (a functionally inert nerve activity is primarily related to BMI in men. as well as in obese in high concentrations. obesity. for cortisol in the pathogenesis of obesity-related hypertension ance. Circulating lev- bility that the impact of obesity-related neural activity on arte.52 Obese humans receptor blockers ameliorate hypertension and associated and subjects with the metabolic syndrome tend to be relatively ­metabolic derangements.60 of neural activity. correlated with waist-to-hip ratio than with BMI.Obesity-Related Hypertension STATE OF THE ART mass or abdominal subcutaneous fat. Over 50 different renin activity.65 Additionally. muscle is elevated in obese normotensive. els of cortisol are variable in obesity. however.57 These observations suggest that the coronary and peripheral arterial vasodilation are more strongly mineralocorticoid action of aldosterone contributes to obesity. Adipokines plasma aldosterone concentrations in obese and hyperten. Adipose tissue is increasingly recognized as an endocrine sive African Americans are relatively high despite low plasma organ with many secretory products. including adipose tissue. lifestyle and the metabolic syndrome remains to be established. It has also been suggested that renin–angiotensin system is associated with high blood pres- increased intrarenal pressures caused by fat surrounding the sure in a model of visceral obesity66. of cardiovascular risk factors. possibly as a conse- quence of increased sympathetic outflow to the kidney. however.54 Increased renal tubular reabsorption of 2 diabetes. quantified by abdominal computed tomography or ultrasound Consistent with a pathogenic role for aldosterone. features of the clinical metabolic syndrome. but to blood glucocorticoid) to cortisol (an active glucocorticoid) in ­target pressure in women.62 Although these observations are provocative. retention and attenuates the rise in blood pressure associated Preliminary evidence suggests that activation of an adipose with dietary-induced obesity. muscle sympathetic nerve activity is low. a role mechanisms include hyperinsulinemia and/or insulin resist.36 Reduced endothelium-dependent metabolic syndrome. In the dog.49 Putative system. eplerenone. Additionally. and plasma aldosterone con. cortisol may increase arterial pressure hypertensive humans. possibly due to sympathetic outflow cate that plasma renin activity and plasma angiotensin II as a consequence of intermittent hypoxia.57 11β-Hydroxysteroid including race and gender.47 These observations raise the possi. tissues. they may not rial pressure is modified by environmental and genetic factors. hypertension. Neural activity to the kidney and skeletal Although not as potent a mineralocorticoid as aldosterone. Endothelium-derived nitric oxide bio- sure.51 concentrations are elevated in obesity. including obesity.55–58 activation is an important determinant of vascular relaxation.67 and in adipose tissue kidneys and increased abdominal pressure associated with from obese hypertensive patients.69 tion and hypertension associated with the development of obesity in dogs fed a high-fat diet. especially upper body obesity. improves endothelial function. of vascular resistance.63. and insulin resistance. renal denervation blunts sodium gen. Visceral fat. factors. We and others have The vascular endothelium plays a major role in the regulation reported that plasma aldosterone is associated with blood pres. renin–angiotensin. aldosterone is independently Vascular endothelial dysfunction is associated with a number associated with hypertension.35.61 This may provide a clue for the relatively low prevalence of The P2-HSD1 mouse with overexpression of HSD1 develops hypertension in Pima Indians. the miner. hypertension a ­matter of conjecture. Several reports indi- ally related to sleep apnea. reflect cortisol’s activity in target tissues. is independently linked to impaired vasoreactivity. and reduce the incidence of type salt sensitive.59 Somewhat paradoxically. particularly among African Americans. by activating the mineralocorticoid receptor. tribute to obesity-related hypertension. recent reports indicate that is not an invariable consequence of obesity-related increases adipokines may directly stimulate aldosterone production. attenuates sodium reten. renin. related hypertension.46. is Activation of the renin–angiotensin system may also con- a risk factor for obstructive sleep apnea. ACE.49 In Pima Indians. and The causes for activation of the sympathetic nervous system activation of the circulating renin–angiotensin–aldosterone in obesity remain uncertain and may be multiple. Impaired pressure-natriuresis may also be related to Impaired endothelial function increased mineralocorticoid activity. For example. despite a high preva. BMI. and hypertension. angiotensin type 1 and type 2 receptors).68 ­visceral obesity may impair natriuresis. The stimulus for increased aldosterone remains ­adipocyte-derived substances have been identified. Hypertension is caus.64 Renal and adrenal mechanisms In obese hypertensive patients. and many AMERICAN JOURNAL OF HYPERTENSION | VOLUME 23 NUMBER 11 | november 2010 1173 . adipose tissue expresses all com- sodium has been attributed to increased sympathetic outflow ponents of the renin–angiotensin system (angiotensino- to the kidney. Weight loss alocorticoid antagonist.

g. and insulin sensitivity. Circulating levels of leptin parallel evidence suggests that systemic free fatty acids. blood pressure is tension can be ameliorated or prevented by chemically diverse not increased in the obese. increased sympathetic ated effects on the hypothalamus and by local peripheral nervous system activity. leptin deficient ob/ob mouse71 or agents that increase insulin sensitivity or have a primary lipid- in obese. teachers. mapped out walking itineraries.82 The towns built ­sporting tribution of body fat is associated with ­insulin ­resistance and facilities. Leptin activates and/or hyperinsulinemia may increase blood pressure include the sympathetic nervous system both by centrally medi. and conversely. and hired 1174 november 2010 | VOLUME 23 NUMBER 11 | AMERICAN JOURNAL OF HYPERTENSION . despite weight loss. may mediate hyper- in normotensive and hypertensive individuals after adjust. Blood pressure and leptin are modestly correlated marily from subcutaneous adipose tissue. Effective strategies for preventing sis in normotensive rats. extend to leptin’s potential sympathetic and cardiovascular has stimulated interest in developing and evaluating strate- actions.” and does not increasing prevalence of obesity.74 lowering effect (e. Although acute infusion of leptin produces natriure. resulting in greater free fatty acid release.76 Because obesity is almost invariably associated with Lifestyle interventions for treatment of obesity include ­emphasis leptin resistance. including childhood obesity. possibly as a consequence been implemented in worksite settings. Some studies that hypertension has recently been described. Increased sympathetic outflow is a putative mechanism by lovastatin). and stimula- by peroneal nerve microneurography) are conflicting. the natriuretic effect is attenuated in and controlling overweight and obesity over a short term have hypertensive and obese Zucker rats.71 Two prospective studies have reported many of these studies have been conducted at supraphysiologic that plasma leptin concentration independently predicts the concentrations of free fatty acids. an antinatriuretic effect of insulin.77 have combined instruction in healthier eating with a structured Preliminary evidence suggest that other adipocyte-­derived approach to increasing physical activity in the workplace. The the weight-reducing effect of leptin is “selective. playgrounds. A metabolic consequence of insulin ­resistance control. centripetal dis. circulating levels of leptin reportedly account for much of the increase in renal sympathetic tone observed in obese human Clinical Management subjects. altered vascular membrane cation transport. several rodent models of experimental hypertension. utes to the metabolic abnormalities and ­possibly to the vascular tion in the leptin receptor induces hyperphagia and obesity in dysfunction associate with upper body obesity.30 Experimental both rodents and humans. it has been postulated that the resistance to on nutrition..73 Although these associations do vations should be considered tentative. the media. Obesity is associated with resistance to insulin-stimulated children involved the mayor.75 In humans. physical activity. focused on either diet or physical activity alone. hyper- tension.80 peptides may also affect arterial pressure. leptin has been the most thoroughly studied. Circulating adipo­ Interventions for preventing obesity in children have recently nectin levels are decreased in obesity-induced insulin been reviewed. leptin deficient humans. However.79 Putative mechanisms by which insulin resistance which leptin may increase arterial pressure.70 and some studies suggest that adiponectin is pro. tive community-based program to prevent obesity in school- sion. and consequently these obser- onset of hypertension. glucose uptake and hyperinsulinemia. chronic systemic and intra­ Whether hypertension is causally related to insulin resist- cerebral administration of leptin increases blood pressure in ance and/or hyperinsulinemia remains an unresolved issue. clofibrate. a comprehensive and innova- Insulin resistance may be a link between obesity and hyperten. In rats.37 Independent of obesity. and behavior modification. ment for fat mass. by reducing appetite and by increasing energy expenditure particularly in upper body/visceral obesity compared with the through sympathetic stimulation to thermogenic tissue. derived pri- fat cell mass.81 Nineteen of 22 studies included in the review resistance. thiazolidinediones. Insulin resistance In two small towns in France. To date. ­scientists. health-care providers.72. gies for obesity prevention. Release of free fatty acids due effects of leptin are primarily mediated by receptors located in to excess adipose tissue lipolysis in upper body obesity contrib- the central nervous system. High tion of vascular smooth muscle growth by insulin. had a small but positive impact on BMI. metformin. The majority of tective against hypertension through an endothelial-­dependent studies were of short term. The absence of leptin or a muta. Nearly all studies resulted in some mechanism. but not in com- bination. tensive mechanisms attributed to insulin resistance. and weight loss increases food providers. These interventions of leptin resistance.71 Transgenic mice overexpressing leptin develop hyper. plasma ­leptin with skeletal muscle nerve activity (measured impaired endothelium-dependent vasodilatation. sports associations.STATE OF THE ART Obesity-Related Hypertension of these substances have been implicated in blood pressure blood pressure. not necessarily indicate causality. various branches of town government. augmented responses to endogenous actions. were school/preschool-based interventions. is an impaired capacity of postprandial hyperinsulinemia to Leptin is a 167 amino acid peptide that promotes weight loss suppress lipolysis.70 The nonobese or lower body obesity.78 A positive relationship between resistin and improvement in diet and physical activity. results of studies of the association of vasoconstrictors.

36. Two medications are currently available in the Stroke Study) trial.Obesity-Related Hypertension STATE OF THE ART sports instructors. whereas it had risen to 17. blood pressure has been shown to decrease β-Blockers may more effectively decrease blood pressure in response to orlistat and to bariatric surgery. prevenons l’obesite des enfants (Together. balanced-deficit macologic treatment of hypertension associated with obesity. Most let’s prevent obesity in children)).90 However.85 low cardiovascular risk was not as pronounced as expected.98 The greatest benefit was reuptake inhibitor. administered either individually or caveats. Incorporation inhibitors to be the most appropriate medication for blood of increased physical activity (e.91 2000 and 2005. which are increased in obese patients. overweight.8%. protection does not compare favorably with other antihyper- cular endothelial function. This total community approach is require treatment with one or more antihypertensive agents now being extended to 200 towns in Europe under the name for blood pressure control. longer term trials.8% in neighbor. As recently reviewed. hypertensive patients. and α-blockers have been asso- reduction of 1 mm Hg/kg of weight loss. in vascular disease in normal weight. tion. low-fat diets.84 A number are not different from nonobese patients. ­suggests there is no compelling reason to use these as first line agents in that the maximum effect of weight loss on blood pressure obesity-related hypertension. goal setting.g. including higher blunt the decrease associated with weight loss. slower rate dyslipidemia. sensitivity and reduce diabetes risk. hypokalemia) are dose related. pharmaco­therapy In the PROGRESS (Perindopril Protection Against Recurrent can be tried. diets.94 Some consider ACE cognitive restructuring and problem solving. but there are a few of ­behavioral strategies.95.89 However. The capacity of thiazide diuretics to lower blood pres- groups. or the >40 kg/m2 or BMI >35 kg/m2 with associated comorbidities. There is little clinical trial data to EPODE (Ensemble. blood pressure low- United States for the treatment of obesity: (i) orlistat—an ering with perindopril resulted in comparable risk reductions inhibitor of pancreatic lipase that reduces intestinal diges.97 trial of diet.84 Orlistat is associated with steatorrhea.96 Although ~2. Families were offered cooking workshops occurs during and soon after weight loss and that this effect is and families at risk were offered individual counseling. AMERICAN JOURNAL OF HYPERTENSION | VOLUME 23 NUMBER 11 | november 2010 1175 .100 Although calcium antagonists do not have reported a diastolic reduction of 0. high-protein The general principles of pharmacotherapy for obese patients diets). and do not make specific recommendations for the phar- ment of obesity (e. Approximately 90% of people who lose weight by diet. For patients with BMI >27 kg/m2 who do not respond to a that study did not target an obese hypertensive population. activity that expends pressure control in obese hypertensive patients. Nevertheless. and behavior therapy. obese. social support. indicate that any one class of agents is superior to others.g. agents has been questioned because their effect on stroke sion incidence.83 sure in obese hypertensive patients is well established. The antihypertensive potencies of lisinopril metformin has recently been shown to cause a small but sta.100 In the short term. ACE inhibitors.101 The use of β-blockers as first line (5–10%) results in reduction of blood pressure and hyperten.69 Reviews of randomized ­trials tensive agents. and improvement in insulin sensitivity and vas.92 and behavioral packages may include food diaries and activity the adverse metabolic effects of diuretics (insulin resistance. and obese tion of fat and (ii) sibutramine—a serotonin–norepinephrine individuals with a history of stroke. in obese than in lean hypertensives. may assist with adherence. records. including trials of bariatric ­surgery. increase insulin ment. exercise. Between attenuated in the long term. However. β-blockers Many predominantly short-term (6-week to 6-month dura.88.. nutrition education.99 style intervention program.93. fallen to 8. an ARB. many if not most obese. and hydrochlorothiazide were reportedly similar in a study tistically significant decrease in BMI when added to a life. compared to placebo. behavioral contracting and reinforce. perhaps because they hypertension per se is generally not considered an indication decrease cardiac output and plasma renin activity. reduction in ­diabetes risk with ACE inhibition in patients with ing regain it within 3–5 years.87 renin inhibitor aliskiren in obese hypertensive patients. review of ciated with improved insulin sensitivity and lipid metabolism. both of for these pharmacologic or surgical approaches. In adolescents. of 223 predominantly white. and possibly angiotensin II receptor blockers. possibly because they had and sibutramine may actually increase blood pressure and higher levels of cardiovascular risk at baseline. the recidivism rate is Ramipril and Rosiglitazone Medication) study suggests that the high. may be associated with weight gain and have negative effects tion) clinical trials document that even moderate weight loss on glucose metabolism. very-low-calorie diets. and weight loss occurs with each of them.500 kcal/week) in the regimen increases the likelihood of the recent DREAM (Diabetes Reduction Assessment with maintaining weight loss. low-carbohydrate diets. blood pressures. control of stimuli that activate eating. meal planning.92 mm Hg and a systolic adverse metabolic side effects.83 guidelines do not recognize obese patients as a special popula- Several different diets have been advocated for the treat.. hypertensive patients ultimately ing comparison towns. the prevalence of overweight in ­children had In addition to weight loss and other lifestyle modifications.86 Bariatric procedures are being Several trials have documented the efficacy of the combina- performed with increasing frequency for patients with BMI tion of hydrochlorothiazide with either an ACE. of eating. observed in those with higher BMIs.

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