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Pathophysiology and Potential Non-Pharmacologic Treatments of Obesity or Kidney Disease Associated Refractory Hypertension

  • Resistant Hypertension (E Pimenta, Section Editor)
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Abstract

Purpose of Review

The review assesses the role of non-pharmacologic therapy for obesity and chronic kidney disease (CKD) associated refractory hypertension (rf HTN).

Recent Findings

Hypertensive patients with markedly heightened sympathetic nervous system (SNS) activity are prone to develop refractory hypertension (rfHTN). Patients with obesity and chronic kidney disease (CKD)-associated HTN have particularly heightened SNS activity and are at high risk of rfHTN. The role of bariatric surgery is increasingly recognized in treatment of obesity.

Summary

Current evidence advocates for a greater role of bariatric surgery in the management of obesity-associated HTN. In contrast, renal denervation does not appear have a role in the management of obesity or CKD-associated HTN. The role of baroreflex activation as adjunctive anti-hypertensive therapy remains to be defined.

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References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. •• Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, et al. Resistant hypertension: diagnosis, evaluation and treatment. A scientific Statement from American Heart Association professional education Committee of the Council of high blood pressure research. Hypertension. 2008;51:1403–9. Most informative review of resistant hypertension

    Article  CAS  PubMed  Google Scholar 

  2. Acelajado MC, Pisoni R, Dudenbostel T, Dell’Italia LJ, Cartmill F, Zhang B, et al. Refractory hypertension: definition, prevalence and patient characteristics. J Clin Hypertens. 2012;14:7–12.

    Article  Google Scholar 

  3. Modolo R, de Faria AP, Sabbatini AR, Barbaro NR, Ritter AM, Moreno H. Refractory and resistant hypertension: characteristics and differences observed in a specialized clinic. J Am Soc Hypertens. 2015;9:397–402.

    Article  PubMed  Google Scholar 

  4. Ogna VF, Pereira E, Sapoval M, Azizi M. Prevalence and risk factors for refractory hypertension in the denervation study. J Hypertens. 2015;33(Suppl 1):e51.

    Article  PubMed  Google Scholar 

  5. Calhoun DA, Booth JN, Oparil S, Irvin MR, Shimbo ID, Lackland DT, et al. Refractory hypertension. Determination of prevalence, risk factors, and comorbidities in a large population-based cohort. Hypertension. 2014;63:451–8.

    Article  CAS  PubMed  Google Scholar 

  6. Siddiqui M, Dudenbostel T, Calhoun DA. Resistant and refractory hypertension: antihypertensive treatment resistance vs treatment failure. Canadian J Cardiol. 2016;32:603–6.

    Article  Google Scholar 

  7. Dudenbostel T, Acelajado MC, Pisoni R, Li P, Oparil S, Calhoun DA. Refractory hypertension: evidence of heightened sympathetic activity as a cause of antihypertensive treatment failure. Hypertension. 2015;66:126–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Weir MR, Townsend RR. Refractory hypertension: an important clinical phenotype. Hypertension. 2014;63:447–8.

    Article  CAS  PubMed  Google Scholar 

  9. •• Grassi G, Mark A, Esler M. The sympathetic nervous system alterations in human hyertension. Circ Res. 2015;116:976–90. This study provides a detailed review of sympathetic nervous system in hypertension

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Mancia G, Grassi G. The autonomic nervous system and hypertension. Circ Res. 2014;114:1804–14.

    Article  CAS  PubMed  Google Scholar 

  11. Judd EK, Oparil S. Novel strategies for the treatment of resistant hypertension. Kidney International Suppl. 2013;3:357–63.

    Article  CAS  Google Scholar 

  12. Garrison RJ, Kannel WB, Stokes III J, Castelli WP. Incidence and precursors of hypertension in young adults: the Framingham offspring study. Prev Med. 1987;16:235–1.

    Article  CAS  PubMed  Google Scholar 

  13. 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;17:904–10.

    Article  PubMed  Google Scholar 

  14. Canning KL, Brown RE, Wharton S, Sharma AM, Kuk JL. Edmonton obesity staging system prevalence and association with weight loss in a publicly funded referral-based obesity. Clinic J Obes. 2015;2015:619734.

    PubMed  Google Scholar 

  15. Guo F, He D, Zhang W, Walton RG. Trends in prevalence, awareness, management, and control of hypertension among United States adults, 1999 to 2010. J Am Coll Cardiol. 2012;60:599–606.

    Article  PubMed  Google Scholar 

  16. Kotsis V, Nilsson P, Grassi G, Mancia G, Redon J, Luft F, et al. WG on obesity, diabetes, the high risk patient, European Society of Hypertension. New developments in the pathogenesis of obesity-induced hypertension. J Hypertens. 2015;33:1499–508.

    Article  CAS  PubMed  Google Scholar 

  17. Movahed MR, Lee JZ, Lim WY, Hashemzadeh M, Hashemzadeh M. Strong independent association between obesity and essential hypertension. Clin Obes. 2016;6:189–92.

    Article  CAS  PubMed  Google Scholar 

  18. Rahmouni K, Haynes WG, Morgan DA, Mark AL. Role of melanocortin-4 receptors in mediating renal sympathoactivation to leptin and insulin. J Neurosci. 2003;23:5998–6004.

    CAS  PubMed  Google Scholar 

  19. Vaněčková I, Maletínská L, Behuliak M, Nagelová V, Zicha J, Kuneš J. Obesity-related hypertension: possible pathophysiological mechanisms. J Endocrinol. 2014;223:R63–78.

    Article  PubMed  CAS  Google Scholar 

  20. Tchernof A, Després JP. Pathophysiology of human visceral obesity: an update. Physiol Rev. 2013;93:359–404.

    Article  CAS  PubMed  Google Scholar 

  21. •• Hall JE, do Carmo JM, da Silva AA, Wang Z, Hall ME. Obesity-induced hypertension: interaction of Neurohumoral and renal mechanisms. Circ Res. 2015;116:991–1006. This review provides a detailed discussion of pathogenesis of obesity associated hypertension

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bochud M, Nussberger J, Bovet P, Maillard MR, Elston RC, Paccaud F, et al. Plasma aldosterone is independently associated with the metabolic syndrome. Hypertension. 2006;48:239–45.

    Article  CAS  PubMed  Google Scholar 

  23. Kidambi S, Kotchen JM, Grim CE, Raff H, Mao J, Singh RJ, Kotchen TA. Association of adrenal steroids with hypertension and the metabolic syndrome in blacks. Hypertension. 2007;49:704–11.

    Article  CAS  PubMed  Google Scholar 

  24. Galmiche G, Pizard A, Gueret A, El Moghrabi SE, Ouvrard-Pascaud A, Berger S, et al. Smooth muscle cell mineralocorticoid receptors are mandatory for aldosterone-salt to induce vascular stiffness. Hypertension. 2014;63:520–6.

    Article  CAS  PubMed  Google Scholar 

  25. Briones AM, Nguyen Dinh Cat A, Callera GE, Yogi A, Burger D, He Y, et al. Adipocytes produce aldosterone through calcineurin-dependent signaling pathways: implications in diabetes mellitus-associated obesity and vascular dysfunction. Hypertension. 2012;59:1069–78.

    Article  CAS  PubMed  Google Scholar 

  26. Huby AC, Antonova G, Groenendyk J, Gomez-Sanchez CE, Bollag WB, Filosa JA, Belin de Chantemèle EJ. Adipocyte-derived hormone leptin is a direct regulator of aldosterone secretion, which promotes endothelial dysfunction and cardiac fibrosis. Circulation. 2015;132:2134–45.

    Article  CAS  PubMed  Google Scholar 

  27. Laffin LJ, Majewski C, Liao C, Bakris GL. Relationship between obesity, hypertension, and aldosterone production in postmenopausal African American women: a pilot study. J Clin Hypertens (Greenwich). 2016;18:1216–21.

    Article  CAS  Google Scholar 

  28. Xie D, Bollag WB. Obesity, hypertension and aldosterone: is leptin the link? J Endocrinol. 2016;230:F7–F11.

    Article  CAS  PubMed  Google Scholar 

  29. Grassi G, Giannnattasio C. Obesity and vascular stiffness: when body fat has an adverse effect on arterial dynamics. J Hypertens. 2005;23:1789–91.

    Article  CAS  PubMed  Google Scholar 

  30. Briet M. Mineralocorticoid receptor, the main player in aldosterone-induced large artery stiffness. Hypertension. 2014;63:442–3.

    Article  CAS  PubMed  Google Scholar 

  31. Williams B, MacDonald TM, Morant S, Webb DJ, Sever P, McInnes G, et al. Spironolactone versus placebo, bisoprolol and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015;386:2059–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Nguyen Dinh Cat A, Briones AM, Callera GE, Yogi A, He Y, Montezano AC, Touyz RM. Adipocyte-derived factors regulate vascular smooth muscle cells through mineralocorticoid and glucocorticoid receptors. Hypertension. 2011;58(3):479–88.

    Article  CAS  PubMed  Google Scholar 

  33. Kaplan NM. The path to prevention and treatment of resistant hypertension. J Am Soc Hypertens. 2015;9:907.

    Article  PubMed  Google Scholar 

  34. Costa MB, Andrade Ezequiel DG, Morais Lovis JC, Oliveira MM, Baumgratz de Paula R. Aldosterone antagonist decreases blood pressure and improves metabolic parameters in obese patients with the metabolic syndrome. J Clin Hypertens (Greenwich). 2010;12:753–5.

    Article  CAS  Google Scholar 

  35. Bloch MJ, Viera AJ. Should patients with obesity and hypertension be treated differently from those who are not obese? Curr Hypertens Rep. 2014;16:418.

    Article  PubMed  CAS  Google Scholar 

  36. Bloch MJ, Basile JN. Ambulatory blood pressure monitoring to diagnose hypertension--an idea whose time has come. J Am Soc Hypertens. 2016;10:89–91.

    Article  PubMed  Google Scholar 

  37. Kalil GZ, Haynes HG. Sympathetic nervous in obesity-related hypertension: mechanisms and clinical implications. Hypertens Rev. 2012;35:4–16.

    Article  CAS  Google Scholar 

  38. Esler M, Straznicky N, Eikelis N, Masuo K, Lambert G, Lambert E. Mechanisms of sympathetic activation in obesity-related hypertension. Hypertension. 2006;48:787–96.

    Article  CAS  PubMed  Google Scholar 

  39. Alvarez GE, Beske SD, Ballard TP, Davy KP. Sympathetic neural activation in visceral obesity. Circulation. 2002;106:2533–6.

    Article  PubMed  Google Scholar 

  40. Alvarez GE, Ballard TP, Beske SD, Davy KP. Subcutaneous obesity is not associated with sympathetic neural activation. Am J Physiol Heart Circ Physiol. 2004;287:H414–8.

    Article  CAS  PubMed  Google Scholar 

  41. Kim SH, Després JP, Koh KK. Obesity and cardiovascular disease: friend or foe? Eur Heart J. 2015;37:3560–8.

    Article  PubMed  Google Scholar 

  42. Lambert E, Straznicky N, Schlaich N, Esler M, Dawood T, Hotchkin E, Lambert G. Differing pattern of sympathoexcitation in normal- weight and obesity-related hypertension. Hypertension. 2007;50:862–8.

    Article  CAS  PubMed  Google Scholar 

  43. Anderson EA, Hoffman RP, Balon TW, Sinkey CA, Mark AL. Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans. J Clin Invest. 1991;87:2246–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Mark AL, Correia M, Morgan DA, Shaffer RA, Haynes WG. State-of-the-art-lecture: obesity-induced hypertension: new concepts from the emerging biology of obesity. Hypertension. 1999;33:537–41.

    Article  CAS  PubMed  Google Scholar 

  45. Lembo G, Napoli R, Capaldo B, Rendina V, Iaccarino G, Volpe M, et al. Abnormal sympathetic overactivity evoked by insulin in the skeletal muscle of patients with essential hypertension. J Clin Invest. 1992;90:24–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Hall JE, da Silva AA, do Carmo JM, Dubinion J, Hamza S, Munusamy S, Smith G, Stec DE. Obesity-induced hypertension: role of sympathetic nervous system, leptin, and melanocortins. J Biol Chem. 2010;285:17271–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Haynes WG, Morgan DA, Walsh SA, Mark AL, Sivitz WI. Receptor-mediated regional sympathetic nerve activation by leptin. J Clin Invest. 1997;100:270–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Hirooka Y, Kishi T, Ito K, Sunagawa K. Potential clinical application of recently discovered brain mechanisms involved in hypertension. Hypertension. 2013;62:995–1002.

    Article  CAS  PubMed  Google Scholar 

  49. Seravalle G, Grassi G. Sympathetic nervous system, hypertension, obesity and metabolic syndrome. High Blood Press Cardiovasc Prev. 2016;23:175–9.

    Article  CAS  PubMed  Google Scholar 

  50. Shimizu H, Inoue K, Mori M. The leptin-dependent and -independent melanocortin signaling system: regulation of feeding and energy expenditure. J Endocrinol. 2007;193:1–9.

    Article  CAS  PubMed  Google Scholar 

  51. •• Rahmouni K. Cardiovascular regulation by the arcuate nucleus of the hypothalamus Neurocircuitry and signaling systems. Hypertension. 2016;67:1064–71. This review provides an uptodate discussion on the role of hypothalamic circuitry in cardiovascular regulation

    Article  CAS  PubMed  Google Scholar 

  52. Carmichael CY, Wainford RD. Hypothalamic signaling mechanisms in hypertension. Curr Hypertens Rep. 2015;17:39.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Sutton AK, Myers Jr MG, Olson DP. The role of PVH circuits in leptin action and energy balance. Annu Rev Physiol. 2016;78:207–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Harlan SM, Rahmouni K. Neuroanatomical determinants of the sympathetic nerve response evoked by leptin. Clin Auton Res. 2013;23:1–7.

    Article  PubMed  Google Scholar 

  55. do Carmo JM, da Silva AA, Wang Z, Fang T, Aberdein N, de Lara Rodriguez CE, Hall JE. Obesity-induced hypertension: brain signaling pathways. Curr Hypertens Rep. 2016;18(7):58.

    Article  PubMed  CAS  Google Scholar 

  56. da Silva AA, do Carmo JM, Hall JE. Role of leptin and central nervous system melanocortins in obesity hypertension. Curr Opin Nephrol Hypertens. 2013;22:135–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Shi Z, Li B, Brooks VL. Role of the paraventricular nucleus of the hypothalamus in the Sympathoexcitatory effects of leptin. Hypertension. 2015;66:1034–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Mark AL. Selective leptin resistance revisited. Am J Physiol Regul Integr Comp Physiol. 2013;305:R566–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Beltowski J. Role of leptin in blood pressure regulation and arterial hypertension. J Hypertens. 2006;24:789–801.

    Article  CAS  PubMed  Google Scholar 

  60. Harlan SM, Rahmouni K. PI3K signaling: a key pathway in the control of sympathetic traffic and arterial pressure by leptin. Mol Metab. 2013;2:69–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Machleidt F, Simon P, Krapalis AF, Hallschmid H, Lehnert H, Sayk F. Experimental hyperleptinemia acutely increases vasoconstrictory sympathetic nerve activity in healthy humans. J Clin Endocrinol Metab. 2013;98:E491–6.

    Article  CAS  PubMed  Google Scholar 

  62. Momin AU, Melikian N, Shah AM, Grieve DJ, Wheatcroft SB, John L, et al. Leptin is an endothelial-independent vasodilator in humans with coronary artery disease: evidence for tissue specificity of leptin resistance. Eur Heart J. 2006;27:2294–9.

    Article  CAS  PubMed  Google Scholar 

  63. Greenfield JR, Miller JW, Keogh JM, Henning E, Satterwhite JH, Cameron GS, et al. Modulation of blood pressure by central melanocortinergic pathways. N Engl J Med. 2009;360:44–52.

    Article  CAS  PubMed  Google Scholar 

  64. SayK F, Heutling D, Dodt C, Iwen KA, Wellhoner JP, Sherag S, et al. Sympathetic function in human carriers of melanocortin-4 receptor gene mutations. J Clin Endocrinol Metab. 2010;95:1998–2002.

    Article  CAS  PubMed  Google Scholar 

  65. Apovian CM. The obesity epidemic—understanding the disease and the treatment. N Engl J Med. 2016;374:177–9.

    Article  PubMed  Google Scholar 

  66. Katagiri H, Yamada T, Oka Y. Adiposity and cardiovascular disorders: disturbance of the regulatory system consisting of humoral and neuronal signals. Circ Res. 2007;101:27–39.

    Article  CAS  PubMed  Google Scholar 

  67. •• Rajapakse NW, Head GA, Kaye DM. Say NO to obesity-related hypertension: role of the L-arginine-nitric oxide pathway. Hypertension. 2016;67:813–9. The review provides a detailed summary of angiotensin II-nitric oxide interaction in obesity associated hypertension

    Article  CAS  PubMed  Google Scholar 

  68. Giam B, Kuruppu S, Head GA, Kaye DM, Rajapakse NW. Effects of dietary l-arginine on nitric oxide bioavailability in obese normotensive and obese hypertensive subjects. Nutrients. 2016;8:E364.

    Article  PubMed  Google Scholar 

  69. Hall ME, do Carmo JM, da Silva AA, Juncos LA, Wang Z, Hall JE. Obesity, hypertension, and chronic kidney disease. Int J Nephrol Renovasc Dis. 2014;7:75–88.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. da Cunha NV, Pinge-Filho P, Panis C, Silva BR, Pernomian L, Grando MD, et al. Decreased endothelial nitric oxide, systemic oxidative stress, and increased sympathetic modulation contribute to hypertension in obese rats. Am J Physiol Heart Circ Physiol. 2014;306:H1472–80.

    Article  PubMed  CAS  Google Scholar 

  71. Harrison DG, Guzik TJ, Lobe HE, Madhur MS, Marvar PJ, Thabet SR, et al. Inflammation, immunity, and hypertension. Hypertension. 2011;57:132–40.

    Article  CAS  PubMed  Google Scholar 

  72. McMaster WG, Kirabo A, Madhur MS, Harrison DG. Inflammation, immunity, and hypertensive end-organ damage. Circ Res. 2015;116:1022–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Wu H, Ghosh S, Perrard XD, Feng L, Garcia CE, Perrard JL, et al. T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity. Circulation. 2007;115:1029–38.

    Article  CAS  PubMed  Google Scholar 

  74. Li H, Li M, Liu P, Wang Y, Zhang H, Li H, et al. Telmisartan ameliorates nephropathy in metabolic syndrome by reducing leptin release from perirenal adipose tissue. Hypertension. 2016;68:478–90.

    Article  CAS  PubMed  Google Scholar 

  75. Grassi G, Seravalle G, Dell’Oro R, Trevano FQ, Bombelli M, Scopelliti F, et al. Comparative effects of candesartan and hydrochlorothiazide on blood pressure, insulin sensitivity, and sympathetic drive in obese hypertensive individuals: results of the CROSS study. J Hypertens. 2003;21:1761–9.

    Article  CAS  PubMed  Google Scholar 

  76. Konno S, Hirooka Y, Kishi T, Sunagawa K. Sympathoinhibitory effects of telmisartan through the reduction of oxidative stress in the rostral ventrolateral medulla of obesity-induced hypertensive rats. J Hypertens. 2012;30:1992–9.

    Article  CAS  PubMed  Google Scholar 

  77. Littlejohn NK, Grobe JL. Opposing tissue-specific roles of angiotensin in the pathogenesis of obesity, and implications for obesity- related hypertension. Am J Physiol, Regul Integr Comp Physiol. 2015;309:R1463–73.

    Article  CAS  Google Scholar 

  78. Gonzaga C, Bertolami A, Bertolami M, Amodeo C, Calhoun D. Obstructive sleep apnea, hypertension and cardiovascular diseases. J Human Hypertens. 2015;29:705–12.

    Article  CAS  Google Scholar 

  79. Palla A, Digiorgio M, Carpenè N, Rossi G, D’Amico I, Santini F, et al. Sleep apnea in morbidly obese patients: prevalence and clinical predictivity. Respiration. 2009;78(2):134–40.

    Article  PubMed  Google Scholar 

  80. Mansukhani M, Kara T, Caples SM, Somers VK. Chemoreflexes, sleep apnea, and sympathetic dysregulation. Curr Hypertens Rep. 2014;16:476.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Konecny T, Kara T, Somers VK. Obstructive sleep apnea and hypertension:an update. Hypertension. 2014;63:203–9.

    Article  CAS  PubMed  Google Scholar 

  82. Lohmeier TE, Iliescu R, Tudorancea I, Cazan R, Cates AW, Georgakopoulos D, Irwin ED. Chronic interactions between carotid baroreceptors and chemoreceptors in obesity hypertension. Hypertension. 2016;68(1):227–35.

    Article  CAS  PubMed  Google Scholar 

  83. •• Abboud F, Kumar R. Obstructive sleep apnea and insights into mechanisms of sympathetic overactivity. J Clin Invest. 2014;124:1454–7. This review provides mechanisms of sustained sympathetic nervous activity in patients with chronic intermittent hypoxia

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest. 1995;96:1897–904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Muxfeldt ES, Margallo V, Costa LM, Guimarães G, Cavalcante AH, Azevedo JC, et al. Effects of continuous positive airway pressure treatment on clinic and ambulatory blood pressures in patients with obstructive sleep apnea and resistant hypertension: a randomized controlled trial. Hypertension. 2015;65(4):736–42.

    Article  CAS  PubMed  Google Scholar 

  86. Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341(6150):1241214.

    Article  PubMed  CAS  Google Scholar 

  87. Cox LM, Yamanishi S, Sohn J, Alekseyenko AV, Leung JM, Cho I. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell. 2014;158:705–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Rautava S, Luoto R, Salminen S, Isolauri E. Microbial contact during pregnancy, intestinal colonization, and human disease. Nat Rev Gastroenterol Hepatol. 2012;9:565–76.

    Article  CAS  PubMed  Google Scholar 

  89. Alang N, Kelly CR. Weight gain after fecal microbiota transplantation. Open Forum Infect Dis. 2015; 2 doi:10.1093/ofid/ofv004.

    PubMed  PubMed Central  Google Scholar 

  90. Kobyliak N, Virchenko O, Falalyeyeva T. Pathophysiological role of host microbiota in the development of obesity. Nutr J. 2016;15:43.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Jess T. Microbiota, antibiotics and obesity. New Engl J Med. 2014;371:2526–8.

    Article  CAS  PubMed  Google Scholar 

  92. Schlaich MP, Socratous F, Hennebry S, Eikelis N, Lambert EA, Straznicky N, et al. Sympathetic activation in chronic renal failure. J Am Soc Nephrol. 2009;20(5):933–9.

    Article  PubMed  Google Scholar 

  93. Rossignol P, Massy ZA, Azizi M, Bakris G, Ritz E, Covic A, et al. ERA-EDTA EURECA-m working group; Red de Investigación Renal (REDINREN) network; Cardiovascular and Renal Clinical Trialists (F-CRIN INI-CRCT) network. The double challenge of resistant hypertension and chronic kidney disease. Lancet. 2015;386:1588–98.

    Article  PubMed  Google Scholar 

  94. Cuche JL, Prinseau J, Selz F, Ruget G, Baglin A. Plasma free, sulfo-and glucuro-conjugated catecholamines in uremic patients. Kidney Int. 1986;30:566–72.

    Article  CAS  PubMed  Google Scholar 

  95. Converse Jr RL, Jacobsen TN, Toto RD, Jost CM, Cosentino F, Fouad-Tarazi F, Victor RG. Sympathetic overactivity in patients with chronic renal failure. N Engl J Med. 1992;327:1912–8.

    Article  PubMed  Google Scholar 

  96. Hausberg M, Kosch M, Harmelink P, Barenbrock M, Hohage H, Kisters K, et al. Sympathetic nerve activity in end-stage renal disease. Circulation. 2002;106:1974–9.

    Article  PubMed  Google Scholar 

  97. Grassi G, Quarti-Trevano F, Seravalle G, Arenare F, Volpe M, Furiani S, et al. Early sympathetic activation in the initial clinical stages of chronic renal failure. Hypertension. 2011;57:846–51.

    Article  CAS  PubMed  Google Scholar 

  98. Shen MJ, Zipes DP. Role of the autonomic nervous system in modulating cardiac arrhythmias. Circ Res. 2014;114:1004–21.

    Article  CAS  PubMed  Google Scholar 

  99. Schlaich MP. Sympathetic activation in chronic kidney disease: out of the shadow. Hypertension. 2011;57:683–5.

    Article  CAS  PubMed  Google Scholar 

  100. Katholi RE, Whitlow PL, Hageman GR, Woods WT. Intrarenal adenosine produces hypertension by activating the sympathetic nervous system via the renal nerves in the dog. J Hypertens. 1984;2:349–59.

    Article  CAS  PubMed  Google Scholar 

  101. Jaén-Águila F, Vargas-Hitos JA, Mediavilla-García JD. Implications of renal denervation therapy in patients with sleep apnea. Int J Hypertens. 2015;2015:408574.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Rejeski WJ, Ip EH, Beroni AG, Bray GA, Evans G, Gregg EW, Zhang Q. Lifestyle change and mobility in obese adults with type 2 diabetes. N Engl J Med. 2012;366:1209–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Goodpaster BH, Delany JP, Otto AD, Kuller L, Vockley J, South-Paul JE, et al. Effects of diet and physical activity interventions on weight loss and cardiometabolic risk factors in severely obese adults: a randomized trial. JAMA. 2010;304:1795–802.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Adams TD, Davidson LE, Litwin SE, Kolotkin RL, LaMonte MJ, Pendleton RC, et al. Health benefits of gastric bypass surgery after 6 years. JAMA. 2012;308:1122–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP, Pothier CE, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012;366:1567–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. •• Bray GA, Frühbeck G, Ryan DH, Wilding JP. Management of obesity. Lancet. 2016;387:1947–56. Extensive review of Obesity Management

    Article  PubMed  Google Scholar 

  107. Wolfe BM, Kvach E, Eckel RH. Treatment of obesity: weight loss and bariatric surgery. Circ Res. 2016;118:1844–55.

    Article  CAS  PubMed  Google Scholar 

  108. Courcoulas AP, Christian NJ, Belle SH, Berk PD, Flum DR, Garcia L, et al. Longitudinal Assessment of Bariatric Surgery (LABS) Consortium. Weight change and health outcomes at 3 years after bariatric surgery among individuals with severe obesity. JAMA. 2013;310:2416–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  109. DeMaria EJ. Bariatric surgery for morbid obesity. N Engl J Med. 2007;356:2176–83.

    Article  CAS  PubMed  Google Scholar 

  110. Douglas IJ, Bhaskaran K, Batterham RL, Smeeth L. Bariatric surgery in the United Kingdom: a cohort study of weight loss and clinical outcomes in routine clinical care. PlosMed. 2015;12:e1001925.

    Google Scholar 

  111. Colquitt JL, Pickett K, Loveman E, Frampton GK. Surgery for weight loss in adults. Cochrane Database Syst Rev. 2014;8:CD003641.

    Google Scholar 

  112. Benaiges D, Más-Lorenzo A, Goday A, Ramon JM, Chillarón JJ, Pedro-Botet J, Flores-Le Roux JA. Laparoscopic sleeve gastrectomy: more than a restrictive bariatric surgery procedure? World J Gastroenterol. 2015;21:11804–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. van Rutte PW, Smulders JF, de Zoete JP, Nienhuijs SW. Outcome of sleeve gastrectomy as a primary bariatric procedure. Br J Surg. 2014;101:661–8.

    Article  PubMed  Google Scholar 

  114. Frühbeck G. Bariatric and metabolic surgery: a shift in eligibility and success criteria. Nat Rev Endocrinol. 2015;11:465–77.

    Article  PubMed  Google Scholar 

  115. Buchwald H, Oien DM. Metabolic/ bariatric surgery worldwide 2011. Obes Surg. 2013;23:427–36.

    Article  PubMed  Google Scholar 

  116. Dogan R, Betzel B, Homan J, Aarts EO, Ploeger N, de Boer H, et al. Long-term effects of laparoscopic roux-en-Y gastric bypass on diabetes mellitus, hypertension and dyslipidemia in morbidly obese patients. Obes Surg. 2014;24:1835–42.

    Article  CAS  PubMed  Google Scholar 

  117. Vidal J, Ibarzabal A, Romero F, Delgado S, Momblán D, Flores L, Lacy A. Type 2 diabetes mellitus and the metabolic syndrome following sleeve gastrectomy in severely obese subjects. Obes Surg. 2008;18:1077–82.

    Article  CAS  PubMed  Google Scholar 

  118. Torgersen Z, Osmolak A, Forse RA. Sleeve gastrectomy and Roux en Y gastric bypass: current state of metabolic surgery. Curr Opin Endocrinol Diabetes Obes. 2014;21:352–7.

    Article  PubMed  Google Scholar 

  119. Peterli R, Borbély Y, Kern B, Gass M, Peters T, Thurnheer M, et al. Early results of the Swiss Multicentre Bypass or Sleeve Study (SM-BOSS): a prospective randomized trial comparing laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass. Ann Surg. 2013;258:690–4.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Lager CJ, Esfandiari NH, Subauste AR, Kraftson AT, Brown MB, Cassidy RB, et al. Roux-en-Y gastric bypass vs. sleeve gastrectomy: balancing the risks of surgery with the benefits of weight loss. Obes Surg. 2016; doi:10.1007/s11695-016-2265-2.

    PubMed Central  Google Scholar 

  121. Nguyen NT, Nguyen B, Gebhart A, Hohmann S. Changes in the makeup of bariatric surgery: a national increase in use of laparoscopic sleeve gastrectomy. J Am Coll Surg. 2013;216:252–7.

    Article  PubMed  Google Scholar 

  122. Reames BN, Finks JF, Bacal D, Carlin AM, Dimick JB. Changes in bariatric surgery procedure use in Michigan, 2006-2013. JAMA. 2014;312:959–61.

    Article  PubMed  PubMed Central  Google Scholar 

  123. Arndtz K, Steed H, Hodson J, Manjunath S. The hidden endoscopic burden of sleeve gastrectomy and its comparison with Roux-en-Y gastric bypass. Ann Gastroenterol. 2016;29:44–9.

    PubMed  PubMed Central  Google Scholar 

  124. Ionut V, Burch M, Youdim A, Bergman RN. Gastrointestinal hormones and bariatric surgery-induced weight loss. Obesity (Silver Spring). 2013;21:1093–103.

    Article  CAS  Google Scholar 

  125. Celio AC, Wu Q, Kasten KR, Manwaring ML, Pories WJ, Spaniolas K. Comparative effectiveness of Roux-en-Y gastric bypass and sleeve gastrectomy in super obese patients. Surg Endosc. 2016; doi:10.1007/s00464-016-4974-y.

    Google Scholar 

  126. Gonzalez-Heredia R, Sanchez-Johnsen L, Valbuena VS, Masrur M, Murphey M, Elli E. Surgical management of super-super obese patients: roux-en-Y gastric bypass versus sleeve gastrectomy. Surg Endosc. 2016;30:2097–102.

    Article  PubMed  Google Scholar 

  127. D'Hondt M, Vanneste S, Pottel H, Devriendt D, Van Rooy F, Vansteenkiste F. Laparoscopic sleeve gastrectomy as a single-stage procedure for the treatment of morbid obesity and the resulting quality of life, resolution of comorbidities, food tolerance, and 6-year weight loss. Surg Endosc. 2011;25:2498–504.

    Article  PubMed  Google Scholar 

  128. Tritsch AM, Bland CM, Hatzigeorgiou C, Sweeney LB, Phillips M. A retrospective review of the medical management of hypertension and diabetes mellitus following sleeve gastrectomy. Obes Surg. 2015;25:642–7.

    Article  PubMed  Google Scholar 

  129. Ricci C, Gaeta M, Rausa E, Asti E, Bandera F, Bonavina L. Long-term effects of bariatric surgery on type II diabetes, hypertension and hyperlipidemia: a meta-analysis and meta-regression study with 5-year follow up. Obes Surg. 2015;25:397–405.

    Article  PubMed  Google Scholar 

  130. Sjöström L, Lindroos AK, Peltonen M, Torgerson J, Bouchard C, Carlsson B, et al. Swedish obese subjects study scientific group. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med. 2004;351:2683–93.

    Article  PubMed  Google Scholar 

  131. Sjöström CD, Peltonen M, Sjöström L. Blood pressure and pulse pressure during long-term weight loss in the obese: the Swedish obese subjects (SOS) intervention study. Obes Res. 2001;9:188–95.

    Article  PubMed  Google Scholar 

  132. Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Brethauer SA, Navaneethan SD, et al. STAMPEDE investigators. Bariatric surgery versus intensive medical therapy for diabetes—3-year outcomes. N Engl J Med. 2014;370:2002–13.

    Article  PubMed  CAS  Google Scholar 

  133. •• Hatoum IJ, Blackstone R, Hunter TD, Francis DM, Steinbuch M, Harris JL, Kaplan LM. Clinical factors associated with remission of obesity-related comorbidities after bariatric surgery. JAMA Surg. 2016;151:130–7. Predictive factors associated with remission of obesity related comorbidities after bariatric surgery

    Article  PubMed  Google Scholar 

  134. Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W, Fahrbach K, Schoelles K. Bariatric surgery a systematic review and meta-analysis. JAMA. 2004;292:1724–37.

    Article  CAS  PubMed  Google Scholar 

  135. Adams ST, Salhab M, Hussain ZI, Miller GV, Leveson SH. Obesity-related hypertension and its remission following gastric bypass surgery-a review of the mechanisms and predictive factors. Blood Press. 2013;22:131–7.

    Article  PubMed  Google Scholar 

  136. Lambert EA, Rice T, Eikelis N, Straznicky NE, Lambert GW, Head GA, et al. Sympathetic activity and markers of cardiovascular risk in nondiabetic severely obese patients: the effect of initial 10% weight loss. Am J Hypertens. 2014;27:1308–15.

    Article  PubMed  Google Scholar 

  137. Carlsson LM, Peltonen M, Ahlin S, Anveden Å, Bouchard C, Carlsson B, et al. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N Engl J Med. 2012;367:695–704.

    Article  CAS  PubMed  Google Scholar 

  138. Ikramuddin S, Korner J, Lee WJ, Connett JE, Inabnet WB, Billington CJ, et al. Roux-en-Y gastric bypass vs intensive medical management for the control of type 2 diabetes, hypertension, and hyperlipidemia: the diabetes surgery study randomized clinical trial. JAMA. 2013;309:2240–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Wilhelm SM, Young J, Kale-Pradhan PB. Effect of bariatric surgery on hypertension: a meta-analysis. Ann Pharmacother. 2014;48:674–82.

    Article  PubMed  Google Scholar 

  140. Cazzo E, Gestic MA, Utrini MP, Machado RR, Pareja JC, Chaim EA. Control of hypertension after Roux-en-Y gastric bypass among obese diabetic patients. Arq Gastroenterol. 2014;51:21–4.

    Article  PubMed  Google Scholar 

  141. Poirier P, Cornier MA, Mazzone T, Stiles S, Cummings S, Klein S, et al. American Heart Association Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Bariatric surgery and cardiovascular risk factors: a scientific statement from the American Heart Association. Circulation. 2011;123:1683–701.

    Article  PubMed  Google Scholar 

  142. Boido A, Ceriani V, Cetta F, Lombardi F, Pontiroli AE. Bariatric surgery and prevention of cardiovascular events and mortality in morbid obesity: mechanisms of action and choice of surgery. Nutr Metabol Cardiovasc Diseas. 2015;25:437–43.

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  144. Bigornia SJ, Farb MG, Tiwari S, Karki S, Hamburg NM, Vita JA, et al. Insulin status and vascular responses to weight loss in obesity. J Am Coll Cardiol. 2013;62:2297–305.

    Article  CAS  PubMed  Google Scholar 

  145. Seravalle G, Colombo M, Perego P, Guardini V, Volpe M, Dell’Oro R, Mancia G, Grassi G. Long-term sympathoinhibitory effects of surgically induced weight loss in severe obese patients. Hypertension. 2014;64:431–7.

    Article  CAS  PubMed  Google Scholar 

  146. Mark AL, Norris AW, Rahmouni K. Sympathetic inhibition after bariatric surgery. Hypertension. 2014;64:235–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Li J, Lai D, Wu D. Laparoscopic Roux-en-Y gastric bypass versus laparoscopic sleeve gastrectomy to treat morbid obesity-related comorbidities: a systematic review and meta-analysis. Obes Surg. 2016;26:429–42.

    Article  PubMed  Google Scholar 

  148. Zhang Y, Wang J, Sun X, Cao Z, Xu X, Liu D, et al. Laparoscopic sleeve gastrectomy versus laparoscopic Roux-en-Y gastric bypass for morbid obesity and related comorbidities: a meta-analysis of 21 studies. Obes Surg. 2015;25:19–26.

    Article  PubMed  Google Scholar 

  149. Puzziferri N, Roshek 3rd TB, Mayo HG, Gallagher R, Belle SH, Livingston EH. Long-term follow-up after bariatric surgery: a systematic review. JAMA. 2014;312:934–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Alvarenga ES, Lo Menzo E, Szomstein S, Rosenthal RJ. Safety and efficacy of 1020 consecutive laparoscopic sleeve gastrectomies performed as a primary treatment modality for morbid obesity. A single-center experience from the metabolic and bariatric surgical accreditation quality and improvement program. Surg Endosc. 2016;30:2673–8.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  152. Peet MM, Isberg EM. The surgical treatment of essential hypertension. J Am Med Assoc. 1946;130:467–73.

    Article  CAS  PubMed  Google Scholar 

  153. Grimson KS, Orgain ES, Anderson B, Broome RA, Longino FH. Results of treatment of patients with hypertension by total thoracic and partial to total lumbar sympathectomy, splanchnicectomy and celiac ganglionectomy. Ann Surg. 1949;129:850–71.

    Article  PubMed Central  Google Scholar 

  154. Smithwick RH, Thompson JE. Splanchnicectomy for essential hypertension; results in 1,266 cases. J Am Med Assoc. 1953;152:1501–4.

    Article  CAS  PubMed  Google Scholar 

  155. Schlaich MP, Esler MD, Fink GD, Osborn JW, Euler DE. Targeting the sympathetic nervous system: critical issues in patient selection, efficacy, and safety of renal denervation. Hypertension. 2014;63:426–32.

    Article  CAS  PubMed  Google Scholar 

  156. Esler M. Renal denervation for treatment of drug-resistant hypertension. Trends in Cardiovascular Medicine. 2015;25(2):107–15.

    Article  PubMed  Google Scholar 

  157. Bhatt DL, Kandzari DE, O'Neill WW, D'Agostino R, Flack JM, Katzen BT, et al. SYMPLICITY HTN-3 investigators. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370(15):1393–401.

    Article  CAS  PubMed  Google Scholar 

  158. Silva JD, Costa M, Gersh BJ, Gonçalves L. Renal denervation in the era of HTN-3. Comprehensive review and glimpse into the future. J Am Soc Hypertens. 2016;10:656–70.

    Article  PubMed  Google Scholar 

  159. Krum H, Schlaich MP, Whitbourn R, Sobotka P, Sadowski J, Bartus K, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicenter safety and proof-of-principle cohort study. Lancet. 2009;373:1275–81.

    Article  PubMed  Google Scholar 

  160. Krum H, Schlaich MP, Sobotka PA, Böhm M, Mahfoud F, Rocha-Singh K, et al. Percutaneous renal denervation in patients with treatment-resistant hypertension: final 3-year report of the Symplicity HTN-1 study. Lancet. 2014;383:622–9.

    Article  PubMed  Google Scholar 

  161. Symplicity HTN-2 Investigators, Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Böhm M. Renal sympathetic denervation in patients with treatment-resistant hypertension (the Symplicity HTN-2 trial): a randomised controlled trial. Lancet. 2010;376:1903–9.

    Article  Google Scholar 

  162. Bakris GL, Townsend RR, Liu M, Cohen SA, D’Agostino R, Flack JM, et al. SYMPLICITY HTN-3 investigators. Impact of renal denervation on 24-hour ambulatory blood pressure: results from SYMPLICITY HTN-3. J Am Coll Cardiol. 2014;64:1071–8.

    Article  PubMed  Google Scholar 

  163. Esler M. Illusions of truths in the Symplicity HTN-3 trial: generic design strengths but neuroscience failings. J Am Soc Hypertens. 2014;8:593–8.

    Article  PubMed  Google Scholar 

  164. Epstein M, de Marchena E. Is the failure of SYMPLICITY HTN-3 trial to meet its efficacy endpoint the “end of the road” for renal denervation? J Am Soc Hypertens. 2015;9:140–9.

    Article  PubMed  Google Scholar 

  165. Flack JM, Bhatt DL, Kandzari DE, Brown D, Brar S, Choi JW, et al. An analysis of the blood pressure and safety outcomes to renal denervation in African-Americans and non-African Americans in the SYMPLICITY HTN-3 trial. J Am Soc Hypertens. 2015;9:769–79.

    Article  PubMed  Google Scholar 

  166. Fadl Elmula FE, Jin Y, Yang WY, Thjis L, Lu YC, Larstorp AC, et al. Meta-analysis of randomized controlled trials of renal denervation in treatment-resistant hypertension. Blood Press. 2015;24:263–74.

    Article  PubMed  Google Scholar 

  167. Persu A, Jin Y, Azizi M, Baelen M, Völz S, Elvan A, et al. Blood pressure changes after renal denervation at 10 European expert centers. J Human Hypertens. 2014;28:150–6.

    Article  Google Scholar 

  168. Vink EE, Verlop WL, Siddiqi L, van Schelven LJ, Oey L, Blankestijn PJ. The effect of percutaneous renal denervation on muscle sympathetic activity in hypertensive patients. Intl J Cardiol. 2014;176:8–12.

    Article  CAS  Google Scholar 

  169. Briasoulis A, Bakris G. Renal denervation after SYMPLICITY HTN-3: where do we go? Can J Cardiol. 2015;31:642–8.

    Article  PubMed  Google Scholar 

  170. Persu A, Kjeldsen S, Staessen J, Azizi M. Renal denervation for treatment of hypertension: a second start and new challenges. Curr Hypertens Rep. 2016;18:6.

    Article  PubMed  CAS  Google Scholar 

  171. Safar ME, Blacher J, Pannier B, Guerin AP, Marchais SJ, Guyonvarc'h PM, London GM. Central pulse pressure and mortality in end-stage renal disease. Hypertension. 2002;39:735–8.

    Article  CAS  PubMed  Google Scholar 

  172. Kiuchi MG, Chen S, Graciano ML, Carreira MA, Kiuchi T, Andrea BR, Lugon JR. Acute effect of renal sympathetic denervation on blood pressure in refractory hypertensive patients with chronic kidney disease. Int J Cardiol. 2015;190:29–31.

    Article  PubMed  Google Scholar 

  173. Ott C, Mahfoud F, Schmid A, Toennes SW, Ewen S, Ditting T, et al. Renal denervation preserves renal function in patients with chronic kidney disease and resistant hypertension. J Hypertens. 2015;33:1261–6.

    Article  CAS  PubMed  Google Scholar 

  174. Mahfoud F, Ukena C, Schmieder RE, Cremers B, Rump LC, Vonend O, et al. Ambulatory blood pressure changes after renal sympathetic denervation in patients with resistant hypertension. Circulation. 2013;128:132–40.

    Article  CAS  PubMed  Google Scholar 

  175. Thorp AA, Schlaich MP. Device-based approaches for renal nerve ablation for hypertension and beyond. Front Physiol. 2015;6:193.

    Article  PubMed  PubMed Central  Google Scholar 

  176. Kjeldsen SE, Persu A, Azizi M. Design of renal denervation studies not confounded by antihypertensive drugs. J Am Soc Hypertens. 2015;9:337–40.

    Article  PubMed  Google Scholar 

  177. White WB, Galis ZS, Henegar J, Kandzari DE, Victor R, Sica D, et al. Renal denervation therapy for hypertension: pathways for moving development forward. J Am Soc Hypertens. 2015;9:341–50.

    Article  PubMed  Google Scholar 

  178. 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;56:1254–8.

    Article  PubMed  Google Scholar 

  179. •• Victor RG. Carotid baroreflex activation therapy for resistant hypertension. Nat Rev Cardiol. 2015;12:451–63. Complete review of baroreflex activated therapy in hypertension

    Article  PubMed  Google Scholar 

  180. Mearns BM. Hypertension: baroreflex activation therapy lowers BP. Nat Rev Cardiol. 2011;8:540.

    Article  PubMed  Google Scholar 

  181. Heusser K, Tank J, Engeli S, Diedrich A, Menne J, Eckert S, et al. Carotid baroreceptor stimulation, sympathetic activity, baroreflex function, and blood pressure in hypertensive patients. Hypertension. 2010;55:619–26.

    Article  CAS  PubMed  Google Scholar 

  182. Lohmeier TE, Ilescu R, Liu B, Henegar JR, Bilkan CM, Irwin ED. Systemic and renal-specific sympathoinhibition in obesity hypertension. Hypertension. 2012;59:331–8.

    Article  CAS  PubMed  Google Scholar 

  183. Georgakopoulos D, Little WC, Abraham WT, Weaver FA, Zile MR. Chronic baroreflex activation: a potential therapeutic approach to heart failure with preserved ejection fraction. J Card Fail. 2011;17:167–78.

    Article  PubMed  Google Scholar 

  184. Mark AL, Somers VK. Obesity, hypoxemia, and hypertension: mechanistic insights and therapeutic implications. Hypertension. 2016;68:24–6.

    Article  CAS  PubMed  Google Scholar 

  185. Bisognano JD, Kaufman CL, Back DS, Lovett EG, de Leeuw P, DEBuT-HT and Rheos Feasibility Trial Investigators. Improved cardiac structure and function with chronic treatment using an implantable device in resistant hypertension: results from European and United States trials of the Rheos system. J Am Coll Cardiol. 2011;57:1787–8.

    Article  PubMed  Google Scholar 

  186. Bisognano JD, Bakris G, Nadim MK, Sanchez L, Kroon AA, Schafer J, de Leeuw PW, Sica DA. Baroreflex activation therapy lowers blood pressure in patients with resistant hypertension: results from the double-blind, randomized, placebo-controlled rheos pivotal trial. J Am Coll Cardiol. 2011;58:765–73.

    Article  PubMed  Google Scholar 

  187. Illig KA, Levy M, Sanchez L, Trachiotis GD, Shanley C, Irwin E, et al. An implantable carotid sinus stimulator for drug-resistant hypertension: surgical technique and short-term outcome from the multicenter phase II Rheos feasibility trial. J Vasc Surg. 2006;44:1213–8.

    Article  PubMed  Google Scholar 

  188. Bakris GL, Nadim NK, Haller H, Lovett EG, Schafer JE, Bisognano JD. Baroreflex activation therapy provides durable benefit in patients with resistant hypertension: results of long-term follow-up in the Rheos Pivotal Trial. J Am Soc Hypertens. 2012;6:152–8.

    Article  PubMed  Google Scholar 

  189. de Leeuw PW, Alnima T, Lovett E, Sica D, Bisognano J, Haller H, Kroon AA. Bilateral or unilateral stimulation for baroreflex activation therapy. Hypertension. 2015;65:187–92.

    Article  PubMed  CAS  Google Scholar 

  190. Alnima T, Goedhart EJ, Seelen R, van der Grinten CP, de Leeuw PW, Kroon AA. Baroreflex activation therapy lowers arterial pressure without apparent stimulation of carotid bodies. Hypertension. 2015;65:1217–22.

    Article  CAS  PubMed  Google Scholar 

  191. Alnima T, de Leeuw PW, Tan FE, Kroon AA, Rheos Pivotal Trial Investigators. Renal responses to long-term carotid baroreflex activation therapy in patients with drug-resistant hypertension. Hypertension. 2013;61:1334–9.

    Article  CAS  PubMed  Google Scholar 

  192. Hoppe UC, Brandt MC, Wachter R, Beige J, Rump LC, Kroon AA, Cates AW, Lovett EG, Haller H. Minimally invasive system for baroreflex activation therapy chronically lowers blood pressure with pacemaker-like safety profile: results from the Barostim neo trial. J Am Soc Hypertens. 2012;6:270–6.

    Article  PubMed  Google Scholar 

  193. Tordoir JH, Scheffers I, Schmidli J, Savolainen H, Liebeskind U, Hansky B, et al. An implantable carotid sinus baroreflex activating system: surgical technique and short-term outcome from a multi-center feasibility trial for the treatment of resistant hypertension. Eur J Vasc Endovasc Surg. 2007;33:414–21.

    Article  CAS  PubMed  Google Scholar 

  194. Halbach M, Hickethier T, Madershahian N, Reuter H, Brandt MC, Hoppe UC, Müller-Ehmsen J. Acute on/off effects and chronic blood pressure reduction after long-term baroreflex activation in resistant hypertension. J Hypertens. 2015;33:1697–703.

    Article  CAS  PubMed  Google Scholar 

  195. Wallbach M, Lehnig LY, Schroer C, Lüders S, Böhning E, Müller GA, et al. Effects of baroreflex activation therapy on ambulatory blood pressure in patients with resistant hypertension. Hypertension. 2016;67:701–9.

    Article  CAS  PubMed  Google Scholar 

  196. Wallbach M, Lehnig LY, Schroer C, Hasenfuss G, Müller GA, Watcher R, Koziolek MJ. Impact of baroreflex activation therapy on renal function: a pilot study. Am J Nephrol. 2014;40:371–80.

    Article  PubMed  Google Scholar 

  197. Wallbach M, Lehning LY, Schroer C, Helms HJ, Lüders S, Patschan D, et al. Effects of baroreflex activation therapy on arterial stiffness and central hemodynamics in patients with resistant hypertension. J Hypertens. 2015;33:181–6.

    Article  CAS  PubMed  Google Scholar 

  198. Beige J, Koziolek MJ, Hennig G, Hamza A, Wendt R, Müller GA, Wallbach M. Baroreflex activation therapy in patients with end-stage renal failure: proof of concept. J Hypertens. 2015;33:2344–9.

    Article  CAS  PubMed  Google Scholar 

  199. Biaggioni I. Interventional approaches to reduce sympathetic activity in resistant hypertension: to ablate or stimulate? Hypertension. 2012;59:194–5.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Cardiology, Tulane University Medical Center, New Orleans, Louisiana, USA

    Thierry H Le Jemtel, Rohan Samson & Abhishek Jaiswal

  2. Division of Cardiology, Tulane University School of Medicine, 1430 Tulane Ave SL-42, New Orleans, LA, 70112, USA

    Thierry H Le Jemtel

  3. Department of Surgery, Ochsner Health System, New Orleans, Louisiana, USA

    William Richardson

  4. Division of Cardiovascular Disease, University of Alabama, Birmingham, AL, USA

    Suzanne Oparil

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Le Jemtel, T.H., Richardson, W., Samson, R. et al. Pathophysiology and Potential Non-Pharmacologic Treatments of Obesity or Kidney Disease Associated Refractory Hypertension. Curr Hypertens Rep 19, 18 (2017). https://doi.org/10.1007/s11906-017-0713-6

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