The Impacts of Obesity on the Cardiovascular and Renal Systems: Cascade of Events and Therapeutic Approaches

Current Hypertension Reports

Volumn 17, Issue 2, 2015, Pages

  Soltani, Zohreh ^a   Washco, Vaughn ^a   Morse, Stephen ^a   Reisin, Efrain ^a  

^a LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER   (United States)

Author keywords

Cardiovascular and renal disease; Hypertension; Metabolic syndrome; Nonpharmacologic and pharmacologic therapy; Obesity

Indexed keywords

AMLODIPINE; ATORVASTATIN; FATTY ACID; HYDROCHLOROTHIAZIDE; LEPTIN; LISINOPRIL; LOSARTAN; NATRIURETIC FACTOR; TRANDOLAPRIL; VERAPAMIL;

ADIPOCYTE; ADIPOSE TISSUE; ADRENERGIC SYSTEM; CARDIOVASCULAR FUNCTION; CARDIOVASCULAR SYSTEM; CORONARY ARTERY DISEASE; HEMODYNAMICS; HUMAN; HYPERTENSION; KIDNEY FUNCTION; KIDNEY INJURY; LIFESTYLE; LIPOTOXICITY; METABOLIC SYNDROME X; OBESITY; PATHOPHYSIOLOGY; RANDOMIZED CONTROLLED TRIAL (TOPIC); RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; SYMPATHETIC NERVE; SYSTEMATIC REVIEW; ANIMAL; CARDIOVASCULAR DISEASES; COMPLICATION; KIDNEY DISEASES;

ANIMALS; CARDIOVASCULAR DISEASES; HUMANS; HYPERTENSION; KIDNEY DISEASES; METABOLIC SYNDROME X; OBESITY;

EID: 84921886615     PISSN: 15226417     EISSN: 15343111     Source Type: Journal    
DOI: 10.1007/s11906-014-0520-2     Document Type: Review

References (165)

1. Abelson P, Kennedy D. The obesity epidemic. Science. 2004;304(5676):1413. English.
2. Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults, 1999–2000. JAMA J Am Med Assoc. 2002;288(14):1723–7. English.
3. Kelly T, Yang W, Chen CS, Reynolds K, He J. Global burden of obesity in 2005 and projections to 2030. Int J Obes. 2008;32(9):1431–7. English.
4. Paolisso G, Manzella D, Rizzo MR, Ragno E, Barbieri M, Varricchio G, et al. Elevated plasma fatty acid concentrations stimulate the cardiac autonomic nervous system in healthy subjects. Am J Clin Nutr. 2000;72(3):723–30. English.
5. He Y, Jiang B, Wang J, Feng K, Chang Q, Fan L, et al. Prevalence of the metabolic syndrome and its relation to cardiovascular disease in an elderly Chinese population. J Am Coll Cardiol. 2006;47(8):1588–94. English.
6. Bray GA. Risks of obesity. Endocrinol Metab Clin N Am. 2003;32:787–804.
7. Korda RJ, Liu B, Clements MS, Bauman AE, Jorm LR, Bambrick HR. Prospective cohort study of body mass index and the risk of hospitalisation: findings from 246 361 participants in the 45 and Up Study. Int J Obes. 2012 September.
8. Morse SA, Zhang RB, Thakur V, Reisin E. Hypertension and the metabolic syndrome. Am J Med Sci. 2005;330(6):303–10. English.
9. Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH. The disease burden associated with overweight and obesity. JAMA J Am Med Assoc. 1999;282(16):1523–9. English.
10. Kissebah AH, Krakower GR. Regional adiposity and morbidity. Physiol Rev. 1994;74(4):761–811. English.
11. Droyvold WB, Midthjell K, Nilsen TI, Holmen J. Change in body mass index and its impact on blood pressure: a prospective population study. Int J Obes (Lond). 2005;29(6):650–5. English.
12. Kotsis VSS, Bouldin M, Low A, Toumanidis S, Zakopoulos N. Impact of obesity on 24-h ambulatory blood pressure and hypertension. Hypertension. 2005;45:602–7.
13. Mikhail N, Golub MS, Tuck ML. Obesity and hypertension. Prog Cardiovasc Dis. 1999;42(1):39–58. English.
14. Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, et al. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med. 1995;1(11):1155–61.
15. Dunbar JC, Hu YG, Lu HQ. Intracerebroventricular leptin increases lumbar and renal sympathetic nerve activity and blood pressure in normal rats. Diabetes. 1997;46(12):2040–3. English.
16. Shek EW, Brands MW, Hall JE. Chronic leptin infusion increases arterial pressure. Hypertension. 1998;31(1):409–14. English.
17. Prior LJ, Eikelis N, Armitage JA, Davern PJ, Burke SL, Montani JP, et al. Exposure to a high-fat diet alters leptin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits. Hypertension. 2010;55(4):862–8.
18. Armitage JA, Burke SL, Prior LJ, Barzel B, Eikelis N, Lim K, et al. Rapid onset of renal sympathetic nerve activation in rabbits fed a high-fat diet. Hypertension. 2012;60(1):163–71. This animal study provides that the course of obesity-related hypertension is fast.
19. Rahmouni K, Haynes WG, Morgan DA, Mark AL. Selective resistance to central neural administration of leptin in agouti obese mice. Hypertension. 2002;39(2):486–90. English.
20. Marsh AJ, Fontes MAP, Killinger S, Pawlak DB, Polson JW, Dampney RAL. Cardiovascular responses evoked by leptin acting on neurons in the ventromedial and dorsomedial hypothalamus. Hypertension. 2003;42(4):488–93. English.
21. Munzberg H, Flier JS, Bjorbaek C. Region-specific leptin resistance within the hypothalamus of diet-induced obese mice. Endocrinology. 2004;145(11):4880–9. English.
22. Ozata M, Ozdemir IC, Licinio J. Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. J Clin Endocrinol Metab. 1999;84(10):3686–95. English.
23. Shankar A, Xiao J. Positive relationship between plasma leptin level and hypertension. Hypertension. 2010;56(4):623–8. English.
24. Lembo G, Vecchione C, Fratta L, Marino G, Trimarco V, DAmati G, et al. Leptin induces direct vasodilation through distinct endothelial mechanisms. Diabetes. 2000;49(2):293–7.
25. Masuo K, Mikami H, Ogihara T, Tuck ML. Weight gain-induced blood pressure elevation. Hypertension. 2000;35(5):1135–40. English.
26. Masuo K, Kawaguchi H, Mikami H, Ogihara T, Tuck ML. Serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation. Hypertension. 2003;42(4):474–80. English.
27. 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(14):5998–6004. English.
28. Greenfield JR, Miller JW, Keogh JM, Henning E, Satterwhite JH, Cameron GS, et al. Modulation of blood pressure by central melanocortinergic pathways. New Engl J Med. 2009;360(1):44–52. English.
29. Rahmouni K, Morgan DA, Morgan GM, Liu XB, Sigmund CD, Mark AL, et al. Hypothalamic PI3K and MAPK differentially mediate regional sympathetic activation to insulin. J Clin Invest. 2004;114(5):652–8. English.
30. Reid IA. Interactions between Ang-Ii, sympathetic nervous-system, and baroreceptor reflexes in regulation of blood-pressure. Am J Physiol. 1992;262(6):E763–78. English.
31. Schutte R, Huisman HW, Schutte AE, Malan NT. Leptin is independently associated with systolic blood pressure, pulse pressure and arterial compliance in hypertensive African women with increased adiposity: the POWIRS study. J Hum Hypertens. 2005;19(7):535–41.
32. 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(2):135–40.
33. Walker WG, Whelton PK, Saito H, Russell RP, Hermann J. Relation between blood pressure and renin, renin substrate, angiotensin II, aldosterone and urinary sodium and potassium in 574 ambulatory subjects. Hypertension. 1979;1(3):287–91.
34. Caulfield M, Lavender P, Newell-Price J, Kamdar S, Farrall M, Clark AJ. Angiotensinogen in human essential hypertension. Hypertension. 1996;28(6):1123–5.
35. Goodfriend TL, Kelley DE, Goodpaster BH, Winters SJ. Visceral obesity and insulin resistance are associated with plasma aldosterone levels in women. Obes Res. 1999;7(4):355–62. English.
36. Goodfriend TL, Calhoun DA. Resistant hypertension, obesity, sleep apnea, and aldosterone—theory and therapy. Hypertension. 2004;43(3):518–24. English.
37. Montani JP, Antic V, Yang Z, Dulloo A. Pathways from obesity to hypertension: from the perspective of a vicious triangle. Int J Obes. 2002;26:S28–38. English.
38. Hall JE, Henegar JR, Dwyer TM, Liu JK, da Silva AA, Kuo JJ, et al. Is obesity a major cause of chronic kidney disease? Adv Ren Replace Ther. 2004;11(1):41–54. English.
39. Crandall DL, Herzlinger HE, Saunders BD, Armellino DC, Kral JG. Distribution of angiotensin II receptors in rat and human adipocytes. J Lipid Res. 1994;35(8):1378–85.
40. Campbell DJ. Circulating and tissue angiotensin systems. J Clin Invest. 1987;79(1):1–6. English.
41. Giacchetti G, Faloia E, Mariniello B, Sardu C, Gatti C, Camilloni MA, et al. Overexpression of the renin-angiotensin system in human visceral adipose tissue in normal and overweight subjects. Am J Hypertens. 2002;15(5):381–8. English.
42. Massiera F, Bloch-Faure M, Ceiler D, Murakami K, Fukamizu A, Gasc JM, et al. Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation. Faseb J. 2001;15(14):2727–9.
43. Cassis LA, Police SB, Yiannikouris F, Thatcher SE. Local adipose tissue renin-angiotensin system. Curr Hypertens Rep. 2008;10(2):93–8. English.
44. Darimont C, Vassaux G, Ailhaud G, Negrel R. Differentiation of preadipose cells—paracrine role of prostacyclin upon stimulation of adipose-cells by angiotensin-Ii. Endocrinology. 1994;135(5):2030–6. English.
45. Engeli S, Bohnke J, Gorzelniak K, Janke J, Schling P, Bader M, et al. Weight loss and the renin-angiotensin-aldosterone system. Hypertension. 2005;45(3):356–62. English.
46. Ehrhart-Bornstein M, Lamounier-Zepter V, Schraven A, Langenbach J, Willenberg HS, Barthel A, et al. Human adipocytes secrete mineralocorticoid-releasing factors. Proc Natl Acad Sci U S A. 2003;100(24):14211–6.
47. Colussi G, Catena C, Lapenna R, Nadalini E, Chiuch A, Sechi LA. Insulin resistance and hyperinsulinemia are related to plasma aldosterone levels in hypertensive patients. Diabetes Care. 2007;30(9):2349–54.
48. Wada T, Ohshima S, Fujisawa E, Koya D, Tsuneki H, Sasaoka T. Aldosterone inhibits insulin-induced glucose uptake by degradation of insulin receptor substrate (IRS) 1 and IRS2 via a reactive oxygen species-mediated pathway in 3T3-L1 adipocytes. Endocrinology. 2009;150(4):1662–9.
49. Bjorntorp P, Rosmond R. Neuroendocrine abnormalities in visceral obesity. Int J Obes. 2000;24:S80–5. English.
50. Rocchini AP, Key J, Bondie D, Chico R, Moorehead C, Katch V, et al. The effect of weight-loss on the sensitivity of blood-pressure to sodium in obese adolescents. New Engl J Med. 1989;321(9):580–5. English.
51. Rocchini AP, Yang JQ, Gokee A. Hypertension and insulin resistance are not directly related in obese dogs. Hypertension. 2004;43(5):1011–6.
52. Hall JE, Brands MW, Zappe DH, Dixon WN, Mizelle HL, Reinhart GA, et al. Hemodynamic and renal responses to chronic hyperinsulinemia in obese, insulin-resistant dogs. Hypertension. 1995;25(5):994–1002. English.
53. Sawicki PT, Baba T, Berger M, Starke A. Normal blood pressure in patients with insulinoma despite hyperinsulinemia and insulin resistance. J Am Soc Nephrol. 1992;3(4 Suppl):S64–8.
54. Liu J, da Silva AA, Tallam LS, Hall JE. Chronic central nervous system hyperinsulinemia and regulation of arterial pressure and food intake. J Hypertens. 2006;24(7):1391–5.
55. Laakso M, Edelman SV, Brechtel G, Baron AD. Decreased effect of insulin to stimulate skeletal-muscle blood-flow in obese man—a novel mechanism for insulin resistance. J Clin Invest. 1990;85(6):1844–52. English.
56. Walsh MF, Ali SS, Sowers JR. Vascular insulin/insulin-like growth factor-1 resistance in female obese Zucker rats. Metabolism. 2001;50(5):607–12. English.
57. Liao J, Soltani Z, Ebenezer P, Isidro-Carrion AA, Zhang RB, Asghar A, et al. Tesaglitazar, a dual peroxisome proliferator-activated receptor agonist (PPAR alpha/gamma), improves metabolic abnormalities and reduces renal injury in obese Zucker rats. Nephron Exp Nephrol. 2010;114(2):E61–8. English.
58. Nolan JJ, Ludvik B, Beerdsen P, Joyce M, Olefsky J. Improvement in glucose-tolerance and insulin-resistance in obese subjects treated with troglitazone. New Engl J Med. 1994;331(18):1188–93. English.
59. Grekin RJ, Dumont CJ, Vollmer AP, Watts SW, Webb RC. Mechanisms in the pressor effects of hepatic portal venous fatty acid infusion. Am J Physiol Reg I. 1997;273(1):R324–30. English.
60. Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, et al. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes. 2000;49(11):1939–45. English.
61. Egan BM, Hennes MM, Stepniakowski KT, O’Shaughnessy IM, Kissebah AH, Goodfriend TL. Obesity hypertension is related more to insulin’s fatty acid than glucose action. Hypertension. 1996;27(3 Pt 2):723–8.
62. Stepniakowski KT, Goodfriend TL, Egan BM. Fatty acids enhance vascular alpha-adrenergic sensitivity. Hypertension. 1995;25(4 Pt 2):774–8.
63. Boden G, She PX, Mozzoli M, Cheung P, Gumireddy K, Reddy P, et al. Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-kappa B pathway in rat liver. Diabetes. 2005;54(12):3458–65. English.
64. Schnabel R, Larson MG, Dupuis J, Lunetta KL, Lipinska I, Meigs JB, et al. Relations of inflammatory biomarkers and common genetic variants with arterial stiffness and wave reflection. Hypertension. 2008;51(6):1651–7.
65. Sprague AH, Khalil RA. Inflammatory cytokines in vascular dysfunction and vascular disease. Biochem Pharmacol. 2009;78(6):539–52.
66. Dessi-Fulgheri P, Sarzani R, Tamburrini P, Moraca A, Espinosa E, Cola G, et al. Plasma atrial natriuretic peptide and natriuretic peptide receptor gene expression in adipose tissue of normotensive and hypertensive obese patients. J Hypertens. 1997;15(12):1695–9. English.
67. Sarzani R, Salvi F, Dessi-Fulgheri P, Rappelli A. Renin-angiotensin system, natriuretic peptides, obesity, metabolic syndrome, and hypertension: an integrated view in humans. J Hypertens. 2008;26(5):831–43. English.
68. Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Wilson PWF, et al. Impact of obesity on plasma natriuretic peptide levels. Circulation. 2004;109(5):594–600. English.
69. Dessi-Fulgheri P, Sarzani R, Rappelli A. The natriuretic peptide system in obesity-related hypertension: new pathophysiological aspects. J Nephrol. 1998;11(6):296–9. English.
70. Sengenes C, Berlan M, De Glisezinski I, Lafontan M, Galitzky J. Natriuretic peptides: a new lipolytic pathway in human adipocytes. Faseb J. 2000;14(10):1345–51. English.
71. Chatterjee TK, Stoll LL, Denning GM, Harrelson A, Blomkalns AL, Idelman G, et al. Proinflammatory phenotype of perivascular adipocytes: influence of high-fat feeding. Circ Res. 2009;104(4):541–9.
72. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante Jr AW. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112(12):1796–808.
73. Lohn M, Dubrovska G, Lauterbach B, Luft FC, Gollasch M, Sharma AM. Periadventitial fat releases a vascular relaxing factor. Faseb J. 2002;16(9):1057–63.
74. Soltis EE, Cassis LA. Influence of perivascular adipose tissue on rat aortic smooth muscle responsiveness. Clin Exp Hypertens A Theory Pract. 1991;13(2):277–96.
75. Gao YJ, Zeng ZH, Teoh K, Sharma AM, Abouzahr L, Cybulsky I, et al. Perivascular adipose tissue modulates vascular function in the human internal thoracic artery. J Thorac Cardiovasc Surg. 2005;130(4):1130–6.
76. Greenstein AS, Khavandi K, Withers SB, Sonoyama K, Clancy O, Jeziorska M, et al. Local inflammation and hypoxia abolish the protective anticontractile properties of perivascular fat in obese patients. Circulation. 2009;119(12):1661–70.
77. Pou KM, Massaro JM, Hoffmann U, Vasan RS, Maurovich-Horvat P, Larson MG, et al. Visceral and subcutaneous adipose tissue volumes are cross-sectionally related to markers of inflammation and oxidative stress: the Framingham Heart Study. Circulation. 2007;116(11):1234–41.
78. Faber DR, van der Graaf Y, Westerink J, Visseren FL. Increased visceral adipose tissue mass is associated with increased C-reactive protein in patients with manifest vascular diseases. Atherosclerosis. 2010;212(1):274–80.
79. Wassmann S, Stumpf M, Strehlow K, Schmid A, Schieffer B, Bohm M, et al. Interleukin-6 induces oxidative stress and endothelial dysfunction by overexpression of the angiotensin II type 1 receptor. Circ Res. 2004;94(4):534–41. English.
80. Nishimatsu H, Suzuki E, Takeda R, Takahashi M, Oba S, Kimura K, et al. Blockade of endogenous proinflammatory cytokines ameliorates endothelial dysfunction in obese Zucker rats. Hypertens Res. 2008;31(4):737–43. English.
81. Zhang R, Reisin E. Obesity-hypertension: the effects on cardiovascular and renal systems. Am J Hypertens. 2000;13(12):1308–14.
82. Milani RV, Lavie CJ, Mehra MR, Ventura HO, Kurtz JD, Messerli FH. Left ventricular geometry and survival in patients with normal left ventricular ejection fraction. Am J Cardiol. 2006;97(7):959–63.
83. Reisin E, Hutchinson HG, editors. Obesity-hypertension: effects on the cardiovascular and renal system—the therapeutic approach. Philadelphia: W.B. Saunders; 1999.
84. Messerli FH, Christie B, Decarvalho JGR, 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. English.
85. Alexander JK, MA. A. Hemodynamic alterations with obesity in man Alpert MA, JK A, editors. New York: Futura Publishing Company; 1998.
86. Ku CS, Lin SL, Wang DJ, Chang SK, Lee WJ. Left-ventricular filling in young normotensive obese adults. Am J Cardiol. 1994;73(8):613–5. English.
87. Messerli FH, Sundgaardriise K, Reisin ED, Dreslinski GR, Ventura HO, Oigman W, et al. Dimorphic cardiac adaptation to obesity and arterial-hypertension. Ann Intern Med. 1983;99(6):757–61. English.
88. Lip GYH, Gammage MD, Beevers DG. Hypertension and the heart. Brit Med Bull. 1994;50(2):299–321. English.
89. Kenchaiah S, Evans JC, Levy D, Wilson PWF, Benjamin EJ, Larson MG, et al. Obesity and the risk of heart failure. New Engl J Med. 2002;347(5):305–13. English.
90. Mohamed-Ali V, Goodrick S, Bulmer K, Holly JM, Yudkin JS, Coppack SW. Production of soluble tumor necrosis factor receptors by human subcutaneous adipose tissue in vivo. Am J Physiol. 1999;277(6 Pt 1):E971–5.
91. Peterson LR, Waggoner AD, Schechtman KB, Meyer T, Gropler RJ, Barzilai B, et al. Alterations in left ventricular structure and function in young healthy obese women: assessment by echocardiography and tissue Doppler imaging. J Am Coll Cardiol. 2004;43(8):1399–404.
92. Artham SM, Lavie CJ, Patel HM, Ventura HO. Impact of obesity on the risk of heart failure and its prognosis. J Cardiometab Syndr. 2008;3(3):155–61.
93. Curtis JP, Selter JG, Wang Y, Rathore SS, Jovin IS, Jadbabaie F, et al. The obesity paradox: body mass index and outcomes in patients with heart failure. Arch Intern Med. 2005;165(1):55–61.
94. Casas-Vara A, Santolaria F, Fernandez-Bereciartua A, Gonzalez-Reimers E, Garcia-Ochoa A, Martinez-Riera A. The obesity paradox in elderly patients with heart failure: analysis of nutritional status. Nutrition. 2012;28(6):616–22.
95. Anker SD, Ponikowski P, Varney S, Chua TP, Clark AL, Webb-Peploe KM, et al. Wasting as independent risk factor for mortality in chronic heart failure. Lancet. 1997;349(9058):1050–3. English.
96. Montani JP, Carroll JF, Dwyer TM, Antic V, Yang Z, Dulloo AG. Ectopic fat storage in heart, blood vessels and kidneys in the pathogenesis of cardiovascular diseases. Int J Obes. 2004;28:S58–65. English.
97. Morabito D, Vallotton MB, Lang U. Obesity is associated with impaired ventricular protein kinase C-MAP kinase signaling and altered ANP mRNA expression in the heart of adult Zucker rats. J Invest Med. 2001;49(4):310–8. English.
98. Cheyne J. A case of apoplexy in which the fleshy part of the heart was converted into fat. Dublin Hosp Rep. 1818;2:216–23.
99. Carpenter HM. Myocardial fat infiltration. Am Heart J. 1962;63:491–6.
100. Lugo M, Putong PB. Metaplasia—an overview. Arch Pathol Lab Med. 1984;108(3):185–9. English.
101. Unger RH, Zhou YT, Orci L. Regulation of fatty acid homeostasis in cells: novel role of leptin. Proc Natl Acad Sci U S A. 1999;96(5):2327–32.
102. Zhou YT, Grayburn P, Karim A, Shimabukuro M, Higa M, Baetens D, et al. Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci U S A. 2000;97(4):1784–9.
103. Sharma S, Adrogue JV, Golfman L, Uray I, Lemm J, Youker K, et al. Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart. Faseb J. 2004;18(14):1692–700.
104. McGavock JM, Lingvay I, Zib I, Tillery T, Salas N, Unger R, et al. Cardiac steatosis in diabetes mellitus: a 1H-magnetic resonance spectroscopy study. Circulation. 2007;116(10):1170–5.
105. Marfella R, Di Filippo C, Portoghese M, Barbieri M, Ferraraccio F, Siniscalchi M, et al. Myocardial lipid accumulation in patients with pressure-overloaded heart and metabolic syndrome. J Lipid Res. 2009;50(11):2314–23.
106. Lakka HM, Lakka TA, Tuomilehto J, Salonen JT. Abdominal obesity is associated with increased risk of acute coronary events in men. Eur Heart J. 2002;23(9):706–13. English.
107. Berenson GS, Srinivasan SR, Bao WH, Newman WP, Tracy RE, Wattigney WA, et al. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. New Engl J Med. 1998;338(23):1650–6. English.
108. Beltowski J. Leptin and atherosclerosis. Atherosclerosis. 2006;189(1):47–60.
109. Kang SM, Kwon HM, Hong BK, Kim D, Kim IJ, Choi EY, et al. Expression of leptin receptor (Ob-R) in human atherosclerotic lesions: potential role in intimal neovascularization. Yonsei Med J. 2000;41(1):68–75.
110. Rogacev KS, Ulrich C, Blomer L, Hornof F, Oster K, Ziegelin M, et al. Monocyte heterogeneity in obesity and subclinical atherosclerosis. Eur Heart J. 2010;31(3):369–76.
111. Nordestgaard BG, Palmer TM, Benn M, Zacho J, Tybaerg-Hansen A, Smith GD, et al. The effect of elevated body mass index on ischemic heart disease risk: causal estimates from a Mendelian randomisation approach. Plos Med. 2012 May;9(5). English. This study shows the causal association between obesity and ischemic heart disease.
112. Bagby SP. Obesity-initiated metabolic syndrome and the kidney: a recipe for chronic kidney disease? J Am Soc Nephrol. 2004;15:2775–91.
113. Chen J, Muntner P, Hamm LL, Jones DW, Batuman V, Fonseca V, et al. The metabolic syndrome and chronic kidney disease in US adults. Ann Intern Med. 2004;140(3):167–74. English.
114. US Renal Data System. USRDS 2005 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. In: National Institute of Diabetes and Digestive and Kidney Diseases NIoH, editor. Bethesda 2005.
115. Kramer H. Obesity and chronic kidney disease. Contrib Nephrol. 2006;151:1–18. English.
116. Gelber RP, Kurth T, Kausz AT, Manson JE, Buring JE, Levey AS, et al. Association between body mass index and CKD in apparently healthy men. Am J Kidney Dis. 2005;46(5):871–80. English.
117. Fox CS, Larson MG, Leip EP, Culleton B, Wilson PWF, Levy D. Predictors of new-onset kidney disease in a community-based population. JAMA. 2004;291(7):844–50. English.
118. Hall JE, Crook ED, Jones DW, Wofford MR, Dubbert PM. Mechanisms of obesity-associated cardiovascular and renal disease. Am J Med Sci. 2002;324(3):127–37. English.
119. Reisin E, Messerli FG, Ventura HO, Frohlich ED. Renal haemodynamic studies in obesity hypertension. J Hypertens. 1987;5(4):397–400.
120. Aros C, Remuzzi G. The renin-angiotensin system in progression, remission and regression of chronic nephropathies. J Hypertens Suppl. 2002;20(3):S45–53.
121. Yoshioka T, Rennke HG, Salant DJ, Deen WM, Ichikawa I. Role of abnormally high transmural pressure in the permselectivity defect of glomerular capillary wall: a study in early passive Heymann nephritis. Circ Res. 1987;61(4):531–8.
122. Schieppati A, Remuzzi G. The future of renoprotection: frustration and promises. Kidney Int. 2003;64(6):1947–55. English.
123. de Paula RB, da Silva AA, Hall JE. Aldosterone antagonism attenuates obesity-induced hypertension and glomerular hyperfiltration. Hypertension. 2004;43(1):41–7. English.
124. Hall JE. The kidney, hypertension, and obesity. Hypertension. 2003;41(3):625–33. English.
125. Shibata S, Nagase M, Yoshida S, Kawachi H, Fujita T. Podocyte as the target for aldosterone: roles of oxidative stress and Sgk1. Hypertension. 2007;49(2):355–64.
126. Chen C, Liang W, Jia J, van Goor H, Singhal PC, Ding G. Aldosterone induces apoptosis in rat podocytes: role of PI3-K/Akt and p38MAPK signaling pathways. Nephron Exp Nephrol. 2009;113(1):e26–34.
127. Wolf G, Ziyadeh FN. Leptin and renal fibrosis. Contrib Nephrol. 2006;151:175–83. English.
128. Wolf G, Hamann A, Han DC, Helmchen U, Thaiss F, Ziyadeh FN, et al. Leptin stimulates proliferation and TGF-beta expression in renal glomerular endothelial cells: potential role in glomerulosclerosis. Kidney Int. 1999;56(3):860–72. English.
129. Zhang XL, Topley N, Ito T, Phillips A. Interleukin-6 regulation of transforming growth factor (TGF)-beta receptor compartmentalization and turnover enhances TGF-beta1 signaling. J Biol Chem. 2005;280(13):12239–45.
130. Takano Y, Yamauchi K, Hayakawa K, Hiramatsu N, Kasai A, Okamura M, et al. Transcriptional suppression of nephrin in podocytes by macrophages: roles of inflammatory cytokines and involvement of the PI3K/Akt pathway. FEBS Lett. 2007;581(3):421–6.
131. Ikezumi Y, Suzuki T, Karasawa T, Kawachi H, Nikolic-Paterson DJ, Uchiyama M. Activated macrophages down-regulate podocyte nephrin and podocin expression via stress-activated protein kinases. Biochem Biophys Res Commun. 2008;376(4):706–11.
132. Jiang T, Wang Z, Proctor G, Moskowitz S, Liebman SE, Rogers T, et al. Diet-induced obesity in C57BL/6J mice causes increased renal lipid accumulation and glomerulosclerosis via a sterol regulatory element-binding protein-1c-dependent pathway. J Biol Chem. 2005;280(37):32317–25.
133. Coimbra TM, Janssen U, Grone HJ, Ostendorf T, Kunter U, Schmidt H, et al. Early events leading to renal injury in obese Zucker (fatty) rats with type II diabetes. Kidney Int. 2000;57(1):167–82. English.
134. Cases A, Coll E. Dyslipidemia and the progression of renal disease in chronic renal failure patients. Kidney Int Suppl. 2005;99:S87–93. English.
135. Keane WF. The role of lipids in renal disease: future challenges. Kidney Int. 2000;57:S27–31. English.
136. Pi-Sunyer FX. NHLBI obesity education initiative expert panel on the identification, evaluation, and treatment of overweight and obesity in adults—the evidence report. Obes Res. 1998;6:51s–209s. English.
137. Redon J, Cifkova R, Laurent S, Nilsson P, Narkiewicz K, Erdine S, et al. The metabolic syndrome in hypertension: European society of hypertension position statement. J Hypertens. 2008;26(10):1891–900. English.
138. Reisin E, Abel R, Modan M, Silverberg DS, Eliahou HE, Modan B. Effect of weight-loss without salt restriction on reduction of blood-pressure in overweight hypertensive patients. New Engl J Med. 1978;298(1):1–6. English.
139. Reisin E, Frohlich ED, Messerli FH, Dreslinski GR, Dunn FG, Jones MM, et al. Cardiovascular changes after weight-reduction in obesity hypertension. Ann Intern Med. 1983;98(3):315–9. English.
140. Neter JE, Stam BE, Kok FJ, Grobbee DE, Geleijnse JM. Influence of weight reduction on blood pressure—a meta-analysis of randomized controlled trials. Hypertension. 2003;42(5):878–84. English.
141. Tuck ML, Sowers J, Dornfeld L, Kledzik G, Maxwell M. The effect of weight-reduction on blood-pressure, plasma-renin activity, and plasma-aldosterone levels in obese patients. New Engl J Med. 1981;304(16):930–3. English.
142. Aucott L, Poobalan A, Smith WCS, Avenell A, Jung R, Broom J. Effects of weight loss in overweight/obese individuals and long-term hypertension outcomes—a systematic review. Hypertension. 2005;45(6):1035–41. English.
143. Jones DW, Miller ME, Wofford MR, Anderson DC, Cameron ME, Willoughby DL, et al. The effect of weight loss intervention on antihypertensive medication requirements in the Hypertension Optimal Treatment (HOT) study. Am J Hypertens. 1999;12(12):1175–80. English.
144. Freedman MR, King J, Kennedy E. Popular diets: a scientific review—executive summary. Obes Res. 2001;9:1S–40S. English.
145. Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM, et al. A clinical trial of the effects of dietary patterns on blood pressure. New Engl J Med. 1997;336(16):1117–24. English.
146. 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. English.
147. Hinderliter A, Sherwood A, Gullette ECD, Babyak M, Waugh R, Georgiades A, et al. Reduction of left ventricular hypertrophy after exercise and weight loss in overweight patients with mild hypertension. Arch Intern Med. 2002;162(12):1333–9. English.
148. Fleischmann EH, Friedrich A, Danzer E, Gallert K, Walter H, Schmieder RE. Intensive training of patients with hypertension is effective in modifying lifestyle risk factors. J Hum Hypertens. 2004;18(2):127–31. English.
149. Sjostrom L, Narbro K, Sjostrom D, Karason K, Larsson B, Wedel H, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. New Engl J Med. 2007;357(8):741–52. English.
150. Klatsky AL, Friedman GD, Siegelaub AB, Gerard MJ. Alcohol consumption and blood-pressure—Kaiser-Permanente Multiphasic Health Examination Data. New Engl J Med. 1977;296(21):1194–200. English.
151. Xin X, He J, Frontini MG, Ogden LG, Motsamai OI, Whelton PK. Effects of alcohol reduction on blood pressure—a meta-analysis of randomized controlled trials. Hypertension. 2001;38(5):1112–7. English.
152. Okubo Y, Miyamoto T, Suwazono Y, Kobayashi E, Nogawa K. Alcohol consumption and blood pressure in Japanese men. Alcohol. 2001;23(3):149–56. English.
153. Reisin E, Tuck ML. Obesity-associated hypertension: hypothesized link between etiology and selection of therapy. Blood Press Monit. 1999;4 Suppl 1:S23–6.
154. Reisin E, Weir MR, Falkner B, Hutchinson HG, Anzalone DA, Tuck ML. Lisinopril versus hydrochlorothiazide in obese hypertensive patients—a multicenter placebo-controlled trial. Hypertension. 1997;30(1):140–5. English.
155. Bakris G, Molitch M, Hewkin A, Kipnes M, Sarafidis P, Fakouhi K, et al. Differences in glucose tolerance between fixed-dose anti hypertensive drug combinations in people with metabolic syndrome. Diabetes Care. 2006;29(12):2592–7. English.
156. van der Zijl NJ, Moors CCM, Goossens GH, Hermans MMH, Blaak EE, Diamant M. Valsartan improves beta-cell function and insulin sensitivity in subjects with impaired glucose metabolism a randomized controlled trial. Diabetes Care. 2011;34(4):845–51. English. This study shows the importance effect of RAAS blockers on insulin secretion/sensitivity.
157. Khan BV, Sola S, Lauten WB, Natarajan R, Hooper WC, Menon RG, et al. Quinapril, an ACE inhibitor, reduces markers of oxidative stress in the metabolic syndrome. Diabetes Care. 2004;27(7):1712–5. English.
158. Jansen PM, Danser JA, Spiering W, van den Meiracker AH. Drug mechanisms to help in managing resistant hypertension in obesity. Curr Hypertens Rep. 2010;12(4):220–5.
159. Sharma AM, Pischon T, Hardt S, Kunz I, Luft FC. Beta-adrenergic receptor blockers and weight gain—a systematic analysis. Hypertension. 2001;37(2):250–4. English.
160. 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. English.
161. Fogari R, Preti P, Zoppi A, Lazzari P, Corradi L, Fogari E, et al. Effects of amlodipine-atorvastatin combination on inflammation markers and insulin sensitivity in normocholesterolemic obese hypertensive patients. Eur J Clin Pharmacol. 2006;62(10):817–22. English.
162. Ferrier KE, Muhlmann MH, Baguet JP, Cameron JD, Jennings GL, Dart AM, et al. Intensive cholesterol reduction lowers blood pressure and large artery stiffness in isolated systolic hypertension. J Am Coll Cardiol. 2002;39(6):1020–5. English.
163. Borghi C, Dormi A, Veronesi M, Immordino V, Ambrosioni E. Use of lipid-lowering drugs and blood pressure control in patients with arterial hypertension. J Clin Hypertens (Greenwich). 2002;4(4):277–85. English.
164. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 Evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2013 Dec 18.
165. Reisin E, Graves JW, Yamal JM, Barzilay JI, Pressel SL, Einhorn PT, et al. Blood pressure control and cardiovascular outcomes in normal-weight, overweight, and obese hypertensive patients treated with three different antihypertensives in ALLHAT. Journal of hypertension. 2014 May 16. Given the lack of enough clinical trials assessing antihypertensive therapy in obese patients, this post hoc analysis of large-scale study like ALLHAT is a useful approach. This study supports that obese hypertensive patients need more attention in terms of therapeutic approach and numerosity of antihypertensive medications.