Skip to main content
SpringerLink
Log in

Treatment of Hypertension in Obese Patients

  • Review Article
  • Published:
American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Obesity is a global pandemic and with its rise, its associated co-morbidities are increasing in prevalence, particularly uncontrolled hypertension. Lifestyle changes should be an anchor for the management of obesity-related hypertension; however, they are difficult to sustain. Drug therapy is often necessary to achieve blood pressure control. Diuretics, inhibitors of the renin–angiotensin system, and dihydropyridine calcium channel blockers are often used as first trio, with subsequent additions of mineralocorticoid receptor antagonists and/or dual alpha/beta blocking agents. While a number of agents are currently available, 50 % of hypertensive patients remain uncontrolled. A number of novel drug and invasive therapies are in development and hold significant potential for the effective management of obesity-related hypertension.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Singer GM, Setaro JF. Secondary hypertension: obesity and the metabolic syndrome. J Clin Hypertens (Greenwich). 2008;10(7):567–74.

    Article  CAS  Google Scholar 

  2. Hajjar I, Kotchen TA. Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988–2000. JAMA. 2003;290(2):199–206.

    Article  PubMed  Google Scholar 

  3. Jordan J, Engeli S, Redon J, Sharma AM, Luft FC, Narkiewicz K, et al. European Society of Hypertension Working Group on Obesity: background, aims and perspectives. J Hypertens. 2007;25(4):897–900.

    Article  PubMed  CAS  Google Scholar 

  4. Garrison RJ, Kannel WB, Stokes J 3rd, Castelli WP. Incidence and precursors of hypertension in young adults: the Framingham Offspring Study. Prev Med. 1987;16(2):235–51.

    Article  PubMed  CAS  Google Scholar 

  5. Biaggioni I. Should we target the sympathetic nervous system in the treatment of obesity-associated hypertension? Hypertension. 2008;51(2):168–71.

    Article  PubMed  CAS  Google Scholar 

  6. Bramlage P, Pittrow D, Wittchen HU, Kirch W, Boehler S, Lehnert H, et al. Hypertension in overweight and obese primary care patients is highly prevalent and poorly controlled. Am J Hypertens. 2004;17(10):904–10.

    Article  PubMed  Google Scholar 

  7. Hall JE, Brands MW, Dixon WN, Smith MJ Jr. Obesity-induced hypertension. Renal function and systemic hemodynamics. Hypertension. 1993;22(3):292–9.

    Article  PubMed  CAS  Google Scholar 

  8. Serne EH, de Jongh RT, Eringa EC, Ijzerman RG, Stehouwer CD. Microvascular dysfunction: a potential pathophysiological role in the metabolic syndrome. Hypertension. 2007;50(1):204–11.

    Article  PubMed  CAS  Google Scholar 

  9. Jonk AM, Houben AJ, de Jongh RT, Serne EH, Schaper NC, Stehouwer CD. Microvascular dysfunction in obesity: a potential mechanism in the pathogenesis of obesity-associated insulin resistance and hypertension. Physiology (Bethesda). 2007;22:252–60.

    Article  CAS  Google Scholar 

  10. Struijker Boudier HA, Cohuet GM, Baumann M, Safar ME. The heart, macrocirculation and microcirculation in hypertension: a unifying hypothesis. J Hypertens Suppl. 2003;21(3):S19–23.

    Google Scholar 

  11. Black PH. The inflammatory response is an integral part of the stress response: Implications for atherosclerosis, insulin resistance, type II diabetes and metabolic syndrome X. Brain Behav Immun. 2003;17(5):350–64.

    Article  PubMed  CAS  Google Scholar 

  12. Megson IL, Webb DJ. Nitric oxide donor drugs: current status and future trends. Expert Opin Investig Drugs. 2002;11(5):587–601.

    Article  PubMed  CAS  Google Scholar 

  13. Levin ER. Endothelins. N Engl J Med. 1995;333(6):356–63.

    Article  PubMed  CAS  Google Scholar 

  14. Mather KJ, Mirzamohammadi B, Lteif A, Steinberg HO, Baron AD. Endothelin contributes to basal vascular tone and endothelial dysfunction in human obesity and type 2 diabetes. Diabetes. 2002;51(12):3517–23.

    Article  PubMed  CAS  Google Scholar 

  15. Hall JE, Hildebrandt DA, Kuo J. Obesity hypertension: role of leptin and sympathetic nervous system. Am J Hypertens. 2001;14(6 Pt 2):103S–15S.

    Article  PubMed  CAS  Google Scholar 

  16. Yang R, Barouch LA. Leptin signaling and obesity: cardiovascular consequences. Circ Res. 2007;101(6):545–59.

    Article  PubMed  CAS  Google Scholar 

  17. van Harmelen V, Elizalde M, Ariapart P, Bergstedt-Lindqvist S, Reynisdottir S, Hoffstedt J, et al. The association of human adipose angiotensinogen gene expression with abdominal fat distribution in obesity. Int J Obes Relat Metab Disord. 2000;24(6):673–8.

    Article  PubMed  CAS  Google Scholar 

  18. Hall JE. The kidney, hypertension, and obesity. Hypertension. 2003;41(3 Pt 2):625–33.

    Article  PubMed  CAS  Google Scholar 

  19. Goodfriend TL, Calhoun DA. Resistant hypertension, obesity, sleep apnea, and aldosterone: theory and therapy. Hypertension. 2004;43(3):518–24.

    Article  PubMed  CAS  Google Scholar 

  20. Hall JE. Mechanisms of abnormal renal sodium handling in obesity hypertension. Am J Hypertens. 1997;10(5 Pt 2):49S–55S.

    Article  PubMed  CAS  Google Scholar 

  21. Trovato GM, Pace P, Martines GF, Trovato FM, Pirri C, Catalano D. Stress, abdominal obesity and intrarenal resistive index in essential hypertension. Clin Ter. 2012;163(4):299–305.

    PubMed  CAS  Google Scholar 

  22. Messerli FH, Christie B, DeCarvalho JG, Aristimuno GG, Suarez DH, Dreslinski GR, et al. Obesity and essential hypertension. Hemodynamics, intravascular volume, sodium excretion, and plasma renin activity. Arch Intern Med. 1981;141(1):81–5.

    Article  PubMed  CAS  Google Scholar 

  23. Stelfox HT, Ahmed SB, Ribeiro RA, Gettings EM, Pomerantsev E, Schmidt U. Hemodynamic monitoring in obese patients: the impact of body mass index on cardiac output and stroke volume. Crit Care Med. 2006;34(4):1243–6.

    Article  PubMed  Google Scholar 

  24. Strazzullo P, Barba G, Cappuccio FP, Siani A, Trevisan M, Farinaro E, et al. Altered renal sodium handling in men with abdominal adiposity: a link to hypertension. J Hypertens. 2001;19(12):2157–64.

    Article  PubMed  CAS  Google Scholar 

  25. Lambert GW, Straznicky NE, Lambert EA, Dixon JB, Schlaich MP. Sympathetic nervous activation in obesity and the metabolic syndrome–causes, consequences and therapeutic implications. Pharmacol Ther. 2010;126(2):159–72.

    Article  PubMed  CAS  Google Scholar 

  26. Centers for Disease Control and Prevention, Division for Heart Disease and Stroke Prevention. Most Americans should consume less sodium. 2012 (Nov 1st, 2012). http://www.cdc.gov/salt/.

  27. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, 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):2560–72.

    Article  PubMed  CAS  Google Scholar 

  28. Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, et al. Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension. 2008;51(6):1403–19.

    Article  PubMed  CAS  Google Scholar 

  29. Isaksson H, Cederholm T, Jansson E, Nygren A, Ostergren J. Therapy-resistant hypertension associated with central obesity, insulin resistance, and large muscle fibre area. Blood Press. 1993;2(1):46–52.

    Article  PubMed  CAS  Google Scholar 

  30. Hall WD. Resistant hypertension, secondary hypertension, and hypertensive crises. Cardiol Clin. 2002;20(2):281–9.

    Article  PubMed  Google Scholar 

  31. Modan M, Almog S, Fuchs Z, Chetrit A, Lusky A, Halkin H. Obesity, glucose intolerance, hyperinsulinemia, and response to antihypertensive drugs. Hypertension. 1991;17(4):565–73.

    Article  PubMed  CAS  Google Scholar 

  32. Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001;344(1):3–10.

    Article  PubMed  CAS  Google Scholar 

  33. Appel LJ, Champagne CM, Harsha DW, Cooper LS, Obarzanek E, Elmer PJ, et al. Effects of comprehensive lifestyle modification on blood pressure control: main results of the PREMIER clinical trial. JAMA. 2003;289(16):2083–93.

    Article  PubMed  Google Scholar 

  34. Whelton SP, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials. Ann Intern Med. 2002;136(7):493–503.

    Article  PubMed  Google Scholar 

  35. Grassi G, Seravalle G, Colombo M, Bolla G, Cattaneo BM, Cavagnini F, et al. Body weight reduction, sympathetic nerve traffic, and arterial baroreflex in obese normotensive humans. Circulation. 1998;97(20):2037–42.

    Article  PubMed  CAS  Google Scholar 

  36. Stevens VJ, Obarzanek E, Cook NR, Lee IM, Appel LJ, Smith West D, et al. Long-term weight loss and changes in blood pressure: results of the Trials of Hypertension Prevention, phase II. Ann Intern Med. 2001;134(1):1–11.

    Article  PubMed  CAS  Google Scholar 

  37. Jordan J, Yumuk V, Schlaich M, Nilsson PM, Zahorska-Markiewicz B, Grassi G, et al. Joint statement of the European Association for the Study of Obesity and the European Society of Hypertension: obesity and difficult to treat arterial hypertension. J Hypertens. 2012;30(6):1047–55.

    Article  PubMed  CAS  Google Scholar 

  38. Uretsky S, Messerli FH, Bangalore S, Champion A, Cooper-Dehoff RM, Zhou Q, et al. Obesity paradox in patients with hypertension and coronary artery disease. Am J Med. 2007;120(10):863–70.

    Article  PubMed  Google Scholar 

  39. Straznicky NE, Grima MT, Lambert EA, Eikelis N, Dawood T, Lambert GW, et al. Exercise augments weight loss induced improvement in renal function in obese metabolic syndrome individuals. J Hypertens. 2011;29(3):553–64.

    Article  PubMed  CAS  Google Scholar 

  40. MacMahon SW, Wilcken DE, Macdonald GJ. The effect of weight reduction on left ventricular mass. A randomized controlled trial in young, overweight hypertensive patients. N Engl J Med. 1986;314(6):334–9.

    Article  PubMed  CAS  Google Scholar 

  41. Haufe S, Utz W, Engeli S, Kast P, Bohnke J, Pofahl M, et al. Left ventricular mass and function with reduced-fat or reduced-carbohydrate hypocaloric diets in overweight and obese subjects. Hypertension. 2012;59(1):70–5.

    Article  PubMed  CAS  Google Scholar 

  42. Blumenthal JA, Sherwood A, Gullette EC, Babyak M, Waugh R, Georgiades A, et al. Exercise and weight loss reduce blood pressure in men and women with mild hypertension: effects on cardiovascular, metabolic, and hemodynamic functioning. Arch Intern Med. 2000;160(13):1947–58.

    Article  PubMed  CAS  Google Scholar 

  43. Carroll JF, Kyser CK. Exercise training in obesity lowers blood pressure independent of weight change. Med Sci Sports Exerc. 2002;34(4):596–601.

    Article  PubMed  Google Scholar 

  44. Whelton PK, Appel LJ, Espeland MA, Applegate WB, Ettinger WH Jr, Kostis JB, 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). TONE Collaborative Research Group. JAMA. 1998;279(11):839–46.

    Article  PubMed  CAS  Google Scholar 

  45. Horvath K, Jeitler K, Siering U, Stich AK, Skipka G, Gratzer TW, et al. Long-term effects of weight-reducing interventions in hypertensive patients: systematic review and meta-analysis. Arch Intern Med. 2008;168(6):571–80.

    Article  PubMed  CAS  Google Scholar 

  46. Guy-Grand B, Drouin P, Eschwege E, Gin H, Joubert JM, Valensi P. Effects of orlistat on obesity-related diseases - a six-month randomized trial. Diabetes Obes Metab. 2004;6(5):375–83.

    Article  PubMed  CAS  Google Scholar 

  47. Torgerson JS, Hauptman J, Boldrin MN, Sjostrom 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):155–61.

    Article  PubMed  CAS  Google Scholar 

  48. Bakris G, Calhoun D, Egan B, Hellmann C, Dolker M, Kingma I. Orlistat improves blood pressure control in obese subjects with treated but inadequately controlled hypertension. J Hypertens. 2002;20(11):2257–67.

    Article  PubMed  CAS  Google Scholar 

  49. Sharma AM, Golay A. Effect of orlistat-induced weight loss on blood pressure and heart rate in obese patients with hypertension. J Hypertens. 2002;20(9):1873–8.

    Article  PubMed  CAS  Google Scholar 

  50. Davidson MH, Hauptman J, DiGirolamo M, Foreyt JP, Halsted CH, Heber D, et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. JAMA. 1999;281(3):235–42.

    Article  PubMed  CAS  Google Scholar 

  51. Sjostrom L, Rissanen A, Andersen T, Boldrin M, Golay A, Koppeschaar HP, et al. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. European Multicentre Orlistat Study Group. Lancet. 1998;352(9123):167–72.

    Article  PubMed  CAS  Google Scholar 

  52. Smith SR, Weissman NJ, Anderson CM, Sanchez M, Chuang E, Stubbe S, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010;363(3):245–56.

    Article  PubMed  CAS  Google Scholar 

  53. Smith SR, Prosser WA, Donahue DJ, Morgan ME, Anderson CM, Shanahan WR. Lorcaserin (APD356), a selective 5-HT(2C) agonist, reduces body weight in obese men and women. Obesity (Silver Spring). 2009;17(3):494–503.

    Article  CAS  Google Scholar 

  54. Fidler MC, Sanchez M, Raether B, Weissman NJ, Smith SR, Shanahan WR, et al. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab. 2011;96(10):3067–77.

    Article  PubMed  CAS  Google Scholar 

  55. Gadde KM, Allison DB, Ryan DH, Peterson CA, Troupin B, Schwiers ML, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9774):1341–52.

    Article  PubMed  CAS  Google Scholar 

  56. Faria AN, Ribeiro Filho FF, Lerario DD, Kohlmann N, Ferreira SR, Zanella MT. Effects of sibutramine on the treatment of obesity in patients with arterial hypertension. Arq Bras Cardiol. 2002;78(2):172–80.

    Article  PubMed  Google Scholar 

  57. McMahon FG, Fujioka K, Singh BN, Mendel CM, Rowe E, Rolston K, 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):2185–91.

    Article  PubMed  CAS  Google Scholar 

  58. Despres JP, Golay A, Sjostrom L. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. 2005;353(20):2121–34.

    Article  PubMed  CAS  Google Scholar 

  59. Pi-Sunyer FX, Aronne LJ, Heshmati HM, Devin J, Rosenstock J. 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. JAMA. 2006;295(7):761–75.

    Article  PubMed  CAS  Google Scholar 

  60. Scheen AJ, Finer N, Hollander P, Jensen MD, Van Gaal LF. Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet. 2006;368(9548):1660–72.

    Article  PubMed  CAS  Google Scholar 

  61. Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rossner S. 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. Lancet. 2005;365(9468):1389–97.

    Article  PubMed  CAS  Google Scholar 

  62. Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W, Fahrbach K, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292(14):1724–37.

    Article  PubMed  CAS  Google Scholar 

  63. Sarkhosh K, Birch DW, Shi X, Gill RS, Karmali S. The impact of sleeve gastrectomy on hypertension: a systematic review. Obes Surg. 2012;22(5):832–7.

    Article  PubMed  Google Scholar 

  64. Sjostrom L, Narbro K, Sjostrom CD, Karason K, Larsson B, Wedel H, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357(8):741–52.

    Article  PubMed  Google Scholar 

  65. Sjostrom CD, Peltonen M, Wedel H, Sjostrom L. Differentiated long-term effects of intentional weight loss on diabetes and hypertension. Hypertension. 2000;36(1):20–5.

    Article  PubMed  CAS  Google Scholar 

  66. Sjostrom CD, Lystig T, Lindroos AK. Impact of weight change, secular trends and ageing on cardiovascular risk factors: 10-year experiences from the SOS study. Int J Obes (Lond). 2011;35(11):1413–20.

    Article  CAS  Google Scholar 

  67. Gress TW, Nieto FJ, Shahar E, Wofford MR, Brancati FL. Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. Atherosclerosis Risk in Communities Study. N Engl J Med. 2000;342(13):905–12.

    Article  PubMed  CAS  Google Scholar 

  68. Sharma AM, Pischon T, Engeli S, Scholze J. Choice of drug treatment for obesity-related hypertension: where is the evidence? J Hypertens. 2001;19(4):667–74.

    Article  PubMed  CAS  Google Scholar 

  69. Zanella MT, Kohlmann O Jr, Ribeiro AB. Treatment of obesity hypertension and diabetes syndrome. Hypertension. 2001;38(3 Pt 2):705–8.

    Article  PubMed  CAS  Google Scholar 

  70. Fonseca VA. Insulin resistance, diabetes, hypertension, and renin–angiotensin system inhibition: reducing risk for cardiovascular disease. J Clin Hypertens (Greenwich). 2006;8(10):713–20. (quiz 21-2).

    Article  CAS  Google Scholar 

  71. Masuo K, Mikami H, Ogihara T, Tuck ML. Weight reduction and pharmacologic treatment in obese hypertensives. Am J Hypertens. 2001;14(6 Pt 1):530–8.

    Article  PubMed  CAS  Google Scholar 

  72. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342(3):145–53.

    Article  PubMed  CAS  Google Scholar 

  73. Shimabukuro M, Tanaka H, Shimabukuro T. Effects of telmisartan on fat distribution in individuals with the metabolic syndrome. J Hypertens. 2007;25(4):841–8.

    Article  PubMed  CAS  Google Scholar 

  74. Hansson L, Lindholm LH, Niskanen L, Lanke J, Hedner T, Niklason A, et al. Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial. Lancet. 1999;353(9153):611–6.

    Article  PubMed  CAS  Google Scholar 

  75. Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359(9311):995–1003.

    Article  PubMed  CAS  Google Scholar 

  76. Oh BH, Mitchell J, Herron JR, Chung J, Khan M, Keefe DL. Aliskiren, an oral renin inhibitor, provides dose-dependent efficacy and sustained 24-hour blood pressure control in patients with hypertension. J Am Coll Cardiol. 2007;49(11):1157–63.

    Article  PubMed  CAS  Google Scholar 

  77. Pool JL, Schmieder RE, Azizi M, Aldigier JC, Januszewicz A, Zidek W, et al. Aliskiren, an orally effective renin inhibitor, provides antihypertensive efficacy alone and in combination with valsartan. Am J Hypertens. 2007;20(1):11–20.

    Article  PubMed  CAS  Google Scholar 

  78. Villamil A, Chrysant SG, Calhoun D, Schober B, Hsu H, Matrisciano-Dimichino L, et al. Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide. J Hypertens. 2007;25(1):217–26.

    Article  PubMed  CAS  Google Scholar 

  79. Shafiq MM, Menon DV, Victor RG. Oral direct renin inhibition: premise, promise, and potential limitations of a new antihypertensive drug. Am J Med. 2008;121(4):265–71.

    Article  PubMed  CAS  Google Scholar 

  80. Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, et al. Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE): rationale and study design. Nephrol Dial Transplant. 2009;24(5):1663–71.

    Article  PubMed  CAS  Google Scholar 

  81. Azizi M, Menard J. Renin inhibitors and cardiovascular and renal protection: an endless quest? Cardiovasc Drugs Ther. 2012.

  82. Harel Z, Gilbert C, Wald R, Bell C, Perl J, Juurlink D, et al. The effect of combination treatment with aliskiren and blockers of the renin–angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis. BMJ. 2012;344:e42.

    Article  PubMed  CAS  Google Scholar 

  83. He J, Ogden LG, Vupputuri S, Bazzano LA, Loria C, Whelton PK. Dietary sodium intake and subsequent risk of cardiovascular disease in overweight adults. JAMA. 1999;282(21):2027–34.

    Article  PubMed  CAS  Google Scholar 

  84. Reisin E, Weir MR, Falkner B, Hutchinson HG, Anzalone DA, Tuck ML. Lisinopril versus hydrochlorothiazide in obese hypertensive patients: a multicenter placebo-controlled trial. Treatment in Obese Patients With Hypertension (TROPHY) Study Group. Hypertension. 1997;30((1 Pt 1)):140–5.

    Article  PubMed  CAS  Google Scholar 

  85. Pollare T, Lithell H, Berne C. A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension. N Engl J Med. 1989;321(13):868–73.

    Article  PubMed  CAS  Google Scholar 

  86. Tuck ML. Obesity, the sympathetic nervous system, and essential hypertension. Hypertension. 1992;19(1 Suppl):I67–77.

    Article  PubMed  CAS  Google Scholar 

  87. Reaven GM, Clinkingbeard C, Jeppesen J, Maheux P, Pei D, Foote J, et al. Comparison of the hemodynamic and metabolic effects of low-dose hydrochlorothiazide and lisinopril treatment in obese patients with high blood pressure. Am J Hypertens. 1995;8(5 Pt 1):461–6.

    Article  PubMed  CAS  Google Scholar 

  88. Ernst ME, Carter BL, Goerdt CJ, Steffensmeier JJ, Phillips BB, Zimmerman MB, et al. Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure. Hypertension. 2006;47(3):352–8.

    Article  PubMed  CAS  Google Scholar 

  89. Khosla N, Chua DY, Elliott WJ, Bakris GL. Are chlorthalidone and hydrochlorothiazide equivalent blood-pressure-lowering medications? J Clin Hypertens (Greenwich). 2005;7(6):354–6.

    Article  Google Scholar 

  90. Menon DV, Arbique D, Wang Z, Adams-Huet B, Auchus RJ, Vongpatanasin W. Differential effects of chlorthalidone versus spironolactone on muscle sympathetic nerve activity in hypertensive patients. J Clin Endocrinol Metab. 2009;94(4):1361–6.

    Article  PubMed  CAS  Google Scholar 

  91. Psaty BM, Lumley T, Furberg CD. Meta-analysis of health outcomes of chlorthalidone-based vs nonchlorthalidone-based low-dose diuretic therapies. JAMA. 2004;292(1):43–4.

    Article  PubMed  CAS  Google Scholar 

  92. Dorsch MP, Gillespie BW, Erickson SR, Bleske BE, Weder AB. Chlorthalidone reduces cardiovascular events compared with hydrochlorothiazide: a retrospective cohort analysis. Hypertension. 2011;57(4):689–94.

    Article  PubMed  CAS  Google Scholar 

  93. Sica DA. Chlorthalidone: has it always been the best thiazide-type diuretic? Hypertension. 2006;47(3):321–2.

    Article  PubMed  CAS  Google Scholar 

  94. Ernst ME, Carter BL, Basile JN. All thiazide-like diuretics are not chlorthalidone: putting the ACCOMPLISH study into perspective. J Clin Hypertens (Greenwich). 2009;11(1):5–10.

    Article  CAS  Google Scholar 

  95. A diuretic for initial treatment of hypertension. Med Lett Drugs Ther. 2009;51(1305):9–10.

    Google Scholar 

  96. Kaplan NM. The choice of thiazide diuretics: why chlorthalidone may replace hydrochlorothiazide. Hypertension. 2009;54(5):951–3.

    Article  PubMed  CAS  Google Scholar 

  97. Kobayashi S, Clemmons DR, Nogami H, Roy AK, Venkatachalam MA. Tubular hypertrophy due to work load induced by furosemide is associated with increases of IGF-1 and IGFBP-1. Kidney Int. 1995;47(3):818–28.

    Article  PubMed  CAS  Google Scholar 

  98. Broekhuysen J, Deger F, Douchamps J, Ducarne H, Herchuelz A. Torasemide, a new potent diuretic. Double-blind comparison with furosemide. Eur J Clin Pharmacol. 1986;31(Suppl):29–34.

    Article  PubMed  Google Scholar 

  99. Nishizaka MK, Zaman MA, Calhoun DA. Efficacy of low-dose spironolactone in subjects with resistant hypertension. Am J Hypertens. 2003;16(11 Pt 1):925–30.

    Article  PubMed  CAS  Google Scholar 

  100. Schinner S, Willenberg HS, Krause D, Schott M, Lamounier-Zepter V, Krug AW, et al. Adipocyte-derived products induce the transcription of the StAR promoter and stimulate aldosterone and cortisol secretion from adrenocortical cells through the Wnt-signaling pathway. Int J Obes (Lond). 2007;31(5):864–70.

    CAS  Google Scholar 

  101. Stas S, Whaley-Connell AT, Sowers JR. Aldosterone and hypertension in the cardiometabolic syndrome. J Clin Hypertens (Greenwich). 2008;10(2):94–6.

    Article  Google Scholar 

  102. Chapman N, Dobson J, Wilson S, Dahlof B, Sever PS, Wedel H, et al. Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension. 2007;49(4):839–45.

    Article  PubMed  CAS  Google Scholar 

  103. de Souza F, Muxfeldt E, Fiszman R, Salles G. Efficacy of spironolactone therapy in patients with true resistant hypertension. Hypertension. 2010;55(1):147–52.

    Article  PubMed  CAS  Google Scholar 

  104. Alvarez-Alvarez B, Abad-Cardiel M, Fernandez-Cruz A, Martell-Claros N. Management of resistant arterial hypertension: role of spironolactone versus double blockade of the renin–angiotensin–aldosterone system. J Hypertens. 2010;28(11):2329–35.

    Article  PubMed  CAS  Google Scholar 

  105. George J, Struthers AD. Evaluation of the aldosterone-blocking agent eplerenone in hypertension and heart failure. Expert Opin Pharmacother. 2007;8(17):3053–9.

    Article  PubMed  CAS  Google Scholar 

  106. Schmieder RE, Gatzka C, Schachinger H, Schobel H, Ruddel H. Obesity as a determinant for response to antihypertensive treatment. BMJ. 1993;307(6903):537–40.

    Article  PubMed  CAS  Google Scholar 

  107. Stoa-Birketvedt G, Thom E, Aarbakke J, Florholmen J. Body fat as a predictor of the antihypertensive effect of nifedipine. J Intern Med. 1995;237(2):169–73.

    Article  PubMed  CAS  Google Scholar 

  108. Hummel D, Raff U, Schwarz TK, Schneider MP, Schmieder RE, Schmidt BM. Dihydropyridine calcium antagonists are associated with increased albuminuria in treatment-resistant hypertensives. J Nephrol. 2010;23(5):563–8.

    PubMed  Google Scholar 

  109. Stein PP, Black HR. Drug treatment of hypertension in patients with diabetes mellitus. Diabetes Care. 1991;14(6):425–48.

    Article  PubMed  CAS  Google Scholar 

  110. Lehtonen A. Doxazosin effects on insulin and glucose in hypertensive patients. The Finnish Multicenter Study Group. Am Heart J. 1991;121(4 Pt 2):1307–11.

    Article  PubMed  CAS  Google Scholar 

  111. Pollare T, Lithell H, Selinus I, Berne C. Application of prazosin is associated with an increase of insulin sensitivity in obese patients with hypertension. Diabetologia. 1988;31(7):415–20.

    Article  PubMed  CAS  Google Scholar 

  112. Davis BR, Cutler JA, Furberg CD, Wright JT, Farber MA, Felicetta JV, et al. Relationship of antihypertensive treatment regimens and change in blood pressure to risk for heart failure in hypertensive patients randomly assigned to doxazosin or chlorthalidone: further analyses from the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial. Ann Intern Med. 2002;137(5 Part 1):313–20.

    Article  PubMed  CAS  Google Scholar 

  113. Grassi G, Cattaneo BM, Seravalle G, Colombo M, Cavagnini F, Mancia G. Obesity and the sympathetic nervous system. Blood Press Suppl. 1996;1:43–6.

    PubMed  CAS  Google Scholar 

  114. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. UK Prospective Diabetes Study Group. BMJ. 1998;317(7160):713–20.

  115. The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med. 1997;157(21):2413–46.

    Google Scholar 

  116. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999;353(9146):9–13.

    Google Scholar 

  117. Gambardella S, Frontoni S, Pellegrinotti M, Testa G, Spallone V, Menzinger G. Carbohydrate metabolism in hypertension: influence of treatment. J Cardiovasc Pharmacol. 1993;22(Suppl 6):S87–97.

    PubMed  Google Scholar 

  118. Sharma AM, Pischon T, Hardt S, Kunz I, Luft FC. Hypothesis: beta-adrenergic receptor blockers and weight gain: A systematic analysis. Hypertension. 2001;37(2):250–4.

    Article  PubMed  CAS  Google Scholar 

  119. Morel Y, Gadient A, Keller U, Vadas L, Golay A. Insulin sensitivity in obese hypertensive dyslipidemic patients treated with enalapril or atenolol. J Cardiovasc Pharmacol. 1995;26(2):306–11.

    Article  PubMed  CAS  Google Scholar 

  120. MacMahon SW, Macdonald GJ, Bernstein L, Andrews G, Blacket RB. Comparison of weight reduction with metoprolol in treatment of hypertension in young overweight patients. Lancet. 1985;1(8440):1233–6.

    Article  PubMed  CAS  Google Scholar 

  121. Dahlof B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet. 2005;366(9489):895–906.

    Article  PubMed  CAS  Google Scholar 

  122. Lindholm LH, Carlberg B, Samuelsson O. Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet. 2005;366(9496):1545–53.

    Article  PubMed  CAS  Google Scholar 

  123. Medical Research Council trial of treatment of hypertension in older adults: principal results. MRC Working Party. BMJ. 1992;304(6824):405–12.

    Google Scholar 

  124. Williams B. The obese hypertensive: the weight of evidence against beta-blockers. Circulation. 2007;115(15):1973–4.

    Article  PubMed  Google Scholar 

  125. Khan N, McAlister FA. Re-examining the efficacy of beta-blockers for the treatment of hypertension: a meta-analysis. CMAJ. 2006;174(12):1737–42.

    Article  PubMed  Google Scholar 

  126. Messerli FH, Grossman E, Goldbourt U. Are beta-blockers efficacious as first-line therapy for hypertension in the elderly? A systematic review. JAMA. 1998;279(23):1903–7.

    Article  PubMed  CAS  Google Scholar 

  127. Messerli FH, Bangalore S, Julius S. Risk/benefit assessment of beta-blockers and diuretics precludes their use for first-line therapy in hypertension. Circulation. 2008;117(20):2706–15. (discussion 15).

    Article  PubMed  Google Scholar 

  128. Cutler JA, Davis BR. Thiazide-type diuretics and beta-adrenergic blockers as first-line drug treatments for hypertension. Circulation. 2008;117(20):2691–704. (discussion 705).

    Article  PubMed  Google Scholar 

  129. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2007;28(12):1462–536.

    PubMed  Google Scholar 

  130. Jacob S, Rett K, Henriksen EJ. Antihypertensive therapy and insulin sensitivity: do we have to redefine the role of beta-blocking agents? Am J Hypertens. 1998;11(10):1258–65.

    Article  PubMed  CAS  Google Scholar 

  131. Bakris GL, Fonseca V, Katholi RE, McGill JB, Messerli FH, Phillips RA, et al. Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial. JAMA. 2004;292(18):2227–36.

    Article  PubMed  CAS  Google Scholar 

  132. Sarafidis PA, Bakris GL. Antihypertensive treatment with beta-blockers and the spectrum of glycaemic control. QJM. 2006;99(7):431–6.

    Article  PubMed  CAS  Google Scholar 

  133. Prichard BN, Graham BR, Owens CW. Moxonidine: a new antiadrenergic antihypertensive agent. J Hypertens Suppl. 1999;17(3):S41–54.

    PubMed  CAS  Google Scholar 

  134. Bousquet P, Greney H, Bruban V, Schann S, Ehrhardt JD, Monassier L, et al. I(1) imidazoline receptors involved in cardiovascular regulation: where are we and where are we going? Ann N Y Acad Sci. 2003;1009:228–33.

    Article  PubMed  CAS  Google Scholar 

  135. Nowak L, Adamczak M, Wiecek A. Blockade of sympathetic nervous system activity by rilmenidine increases plasma adiponectin concentration in patients with essential hypertension. Am J Hypertens. 2005;18(11):1470–5.

    Article  PubMed  CAS  Google Scholar 

  136. Fenton C, Keating GM, Lyseng-Williamson KA. Moxonidine: a review of its use in essential hypertension. Drugs. 2006;66(4):477–96.

    Article  PubMed  CAS  Google Scholar 

  137. Sharma AM, Wagner T, Marsalek P. Moxonidine in the treatment of overweight and obese patients with the metabolic syndrome: a postmarketing surveillance study. J Hum Hypertens. 2004;18(9):669–75.

    Article  PubMed  CAS  Google Scholar 

  138. Chazova I, Almazov VA, Shlyakhto E. Moxonidine improves glycaemic control in mildly hypertensive, overweight patients: a comparison with metformin. Diabetes Obes Metab. 2006;8(4):456–65.

    Article  PubMed  CAS  Google Scholar 

  139. Cohn JN, Pfeffer MA, Rouleau J, Sharpe N, Swedberg K, Straub M, et al. Adverse mortality effect of central sympathetic inhibition with sustained-release moxonidine in patients with heart failure (MOXCON). Eur J Heart Fail. 2003;5(5):659–67.

    Article  PubMed  CAS  Google Scholar 

  140. Wulffele MG, Kooy A, de Zeeuw D, Stehouwer CD, Gansevoort RT. The effect of metformin on blood pressure, plasma cholesterol and triglycerides in type 2 diabetes mellitus: a systematic review. J Intern Med. 2004;256(1):1–14.

    Article  PubMed  CAS  Google Scholar 

  141. Wulffele MG, Kooy A, Lehert P, Bets D, Donker AJ, Stehouwer CD. Does metformin decrease blood pressure in patients with Type 2 diabetes intensively treated with insulin? Diabet Med. 2005;22(7):907–13.

    Article  PubMed  CAS  Google Scholar 

  142. Uwaifo GI, Ratner RE. Differential effects of oral hypoglycemic agents on glucose control and cardiovascular risk. Am J Cardiol. 2007;99(4A):51B–67B.

    Article  PubMed  CAS  Google Scholar 

  143. Mazzone T, Meyer PM, Feinstein SB, Davidson MH, Kondos GT, D’Agostino RB Sr, et al. Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial. JAMA. 2006;296(21):2572–81.

    Article  PubMed  CAS  Google Scholar 

  144. Stocker DJ, Taylor AJ, Langley RW, Jezior MR, Vigersky RA. A randomized trial of the effects of rosiglitazone and metformin on inflammation and subclinical atherosclerosis in patients with type 2 diabetes. Am Heart J. 2007;153(3):445, e1–6.

    Google Scholar 

  145. Nissen SE, Nicholls SJ, Wolski K, Nesto R, Kupfer S, Perez A, et al. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA. 2008;299(13):1561–73.

    Article  PubMed  CAS  Google Scholar 

  146. Nakamura T, Funahashi T, Yamashita S, Nishida M, Nishida Y, Takahashi M, et al. Thiazolidinedione derivative improves fat distribution and multiple risk factors in subjects with visceral fat accumulation—double-blind placebo-controlled trial. Diabetes Res Clin Pract. 2001;54(3):181–90.

    Article  PubMed  CAS  Google Scholar 

  147. Astrup A, Carraro R, Finer N, Harper A, Kunesova M, Lean ME, et al. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int J Obes (Lond). 2012;36(6):843–54.

    Article  CAS  Google Scholar 

  148. Sarafidis PA. Metabolic syndrome and arterial stiffness: evidence for gender disparity and early effects of non-traditional risk factors? J Hypertens. 2007;25(5):935–8.

    Article  PubMed  CAS  Google Scholar 

  149. Feig PU, Roy S, Cody RJ. Antihypertensive drug development: current challenges and future opportunities. J Am Soc Hypertens. 2010;4(4):163–73.

    Article  PubMed  Google Scholar 

  150. Laurent S, Schlaich M, Esler M. New drugs, procedures, and devices for hypertension. Lancet. 2012;380(9841):591–600.

    Article  PubMed  CAS  Google Scholar 

  151. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42(6):1206–52.

    Article  PubMed  CAS  Google Scholar 

  152. Rosendorff C, Black HR, Cannon CP, Gersh BJ, Gore J, Izzo JL Jr, et al. Treatment of hypertension in the prevention and management of ischemic heart disease: a scientific statement from the American Heart Association Council for High Blood Pressure Research and the Councils on Clinical Cardiology and Epidemiology and Prevention. Circulation. 2007;115(21):2761–88.

    Article  PubMed  Google Scholar 

  153. Cooper-DeHoff RM, Gong Y, Handberg EM, Bavry AA, Denardo SJ, Bakris GL, et al. Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease. JAMA. 2010;304(1):61–8.

    Article  PubMed  CAS  Google Scholar 

  154. Mann SJ. Drug therapy for resistant hypertension: simplifying the approach. J Clin Hypertens (Greenwich). 2011;13(2):120–30.

    Article  Google Scholar 

  155. Wenzel UO, Krebs C. Management of arterial hypertension in obese patients. Curr Hypertens Rep. 2007;9(6):491–7.

    Article  PubMed  CAS  Google Scholar 

  156. Frohlich ED. Clinical management of the obese hypertensive patient. Cardiol Rev. 2002;10(3):127–38.

    Article  PubMed  Google Scholar 

  157. Ng MM, Sica DA, Frishman WH. Rheos: an implantable carotid sinus stimulation device for the nonpharmacologic treatment of resistant hypertension. Cardiol Rev. 2011;19(2):52–7.

    Article  PubMed  Google Scholar 

  158. Scheffers IJ, Kroon AA, Schmidli J, Jordan J, Tordoir JJ, Mohaupt MG, et al. Novel baroreflex activation therapy in resistant hypertension: results of a European multi-center feasibility study. J Am Coll Cardiol. 2010;56(15):1254–8.

    Article  PubMed  Google Scholar 

  159. Lohmeier TE, Iliescu R. Chronic lowering of blood pressure by carotid baroreflex activation: mechanisms and potential for hypertension therapy. Hypertension. 2011;57(5):880–6.

    Article  PubMed  CAS  Google Scholar 

  160. DiBona GF, Esler M. Translational medicine: the antihypertensive effect of renal denervation. Am J Physiol Regul Integr Comp Physiol. 2010;298(2):R245–53.

    Article  PubMed  CAS  Google Scholar 

  161. Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009;373(9671):1275–81.

    Article  PubMed  Google Scholar 

  162. Azizi M, Amar L, Menard J. Aldosterone synthase inhibition in humans. Nephrol Dial Transplant. 2013;28(1):36–43.

    Google Scholar 

  163. Black HR, Bakris GL, Weber MA, Weiss R, Shahawy ME, Marple R, et al. Efficacy and safety of darusentan in patients with resistant hypertension: results from a randomized, double-blind, placebo-controlled dose-ranging study. J Clin Hypertens (Greenwich). 2007;9(10):760–9.

    Article  CAS  Google Scholar 

  164. Weber MA, Black H, Bakris G, Krum H, Linas S, Weiss R, et al. A selective endothelin-receptor antagonist to reduce blood pressure in patients with treatment-resistant hypertension: a randomised, double-blind, placebo-controlled trial. Lancet. 2009;374(9699):1423–31.

    Article  PubMed  CAS  Google Scholar 

  165. Bakris GL, Lindholm LH, Black HR, Krum H, Linas S, Linseman JV, et al. Divergent results using clinic and ambulatory blood pressures: report of a darusentan-resistant hypertension trial. Hypertension. 2010;56(5):824–30.

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

Authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Division of Endocrinology, Metabolism and Clinical Nutrition, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI, 53226, USA

    Srividya Kidambi & Theodore A. Kotchen

  2. Clement A. Zablocki VA Medical Center, Milwaukee, WI, USA

    Srividya Kidambi

Authors
  1. Srividya Kidambi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Theodore A. Kotchen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Srividya Kidambi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kidambi, S., Kotchen, T.A. Treatment of Hypertension in Obese Patients. Am J Cardiovasc Drugs 13, 163–175 (2013). https://doi.org/10.1007/s40256-013-0008-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40256-013-0008-5

Keywords

Search

Navigation