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Current Hypertension Reports
Published in: Current Hypertension Reports 2/2015

01-02-2015 | Hypertension and Obesity (E Reisin, Section Editor)

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

Authors: Zohreh Soltani, Vaughn Washco, Stephen Morse, Efrain Reisin

Published in: Current Hypertension Reports | Issue 2/2015

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Abstract

There is a neglected epidemic of both obesity and metabolic syndrome in industrialized and unindustrialized countries all over the globe. Both conditions are associated with a high incidence of other serious pathologies, such as cardiovascular and renal diseases. In this article, we review the potential underlying mechanisms by which obesity and metabolic syndrome promote hypertension, including changes in cardiovascular–renal physiology induced by leptin, the sympathetic nervous system, the renin–angiotensin–aldosterone system, insulin resistance, free fatty acids, natriuretic peptides, and proinflammatory cytokines. We also discuss the potential underlying mechanisms by which obesity promotes other cardiovascular and renal conditions, as well as available nonpharmacologic and pharmacologic approaches for treating obesity-induced hypertension. The findings presented herein suggest that adipocytes may be a key regulator of cardiovascular and renal function.
Literature
1.
Abelson P, Kennedy D. The obesity epidemic. Science. 2004;304(5676):1413. English.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
13.
Mikhail N, Golub MS, Tuck ML. Obesity and hypertension. Prog Cardiovasc Dis. 1999;42(1):39–58. English.PubMed
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.PubMed
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.PubMed
16.
Shek EW, Brands MW, Hall JE. Chronic leptin infusion increases arterial pressure. Hypertension. 1998;31(1):409–14. English.PubMed
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.PubMed
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. PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
23.
Shankar A, Xiao J. Positive relationship between plasma leptin level and hypertension. Hypertension. 2010;56(4):623–8. English.PubMed
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.PubMed
25.
Masuo K, Mikami H, Ogihara T, Tuck ML. Weight gain-induced blood pressure elevation. Hypertension. 2000;35(5):1135–40. English.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMedCentralPubMed
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.PubMed
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.PubMed
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.PubMedCentralPubMed
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.PubMed
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.PubMed
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.PubMed
36.
Goodfriend TL, Calhoun DA. Resistant hypertension, obesity, sleep apnea, and aldosterone—theory and therapy. Hypertension. 2004;43(3):518–24. English.PubMed
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.PubMed
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.PubMed
40.
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.PubMed
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.PubMed
43.
Cassis LA, Police SB, Yiannikouris F, Thatcher SE. Local adipose tissue renin-angiotensin system. Curr Hypertens Rep. 2008;10(2):93–8. English.PubMedCentralPubMed
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.PubMed
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.PubMed
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.PubMedCentralPubMed
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.PubMed
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.PubMed
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.PubMed
51.
Rocchini AP, Yang JQ, Gokee A. Hypertension and insulin resistance are not directly related in obese dogs. Hypertension. 2004;43(5):1011–6.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMedCentralPubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
62.
Stepniakowski KT, Goodfriend TL, Egan BM. Fatty acids enhance vascular alpha-adrenergic sensitivity. Hypertension. 1995;25(4 Pt 2):774–8.PubMed
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.PubMed
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.PubMedCentralPubMed
65.
Sprague AH, Khalil RA. Inflammatory cytokines in vascular dysfunction and vascular disease. Biochem Pharmacol. 2009;78(6):539–52.PubMedCentralPubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMedCentralPubMed
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.PubMedCentralPubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
81.
Zhang R, Reisin E. Obesity-hypertension: the effects on cardiovascular and renal systems. Am J Hypertens. 2000;13(12):1308–14.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
88.
Lip GYH, Gammage MD, Beevers DG. Hypertension and the heart. Brit Med Bull. 1994;50(2):299–321. English.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
100.
Lugo M, Putong PB. Metaplasia—an overview. Arch Pathol Lab Med. 1984;108(3):185–9. English.PubMed
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.PubMedCentralPubMed
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.PubMedCentralPubMed
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.PubMed
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.PubMed
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.PubMedCentralPubMed
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.PubMed
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.PubMed
108.
Beltowski J. Leptin and atherosclerosis. Atherosclerosis. 2006;189(1):47–60.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
119.
Reisin E, Messerli FG, Ventura HO, Frohlich ED. Renal haemodynamic studies in obesity hypertension. J Hypertens. 1987;5(4):397–400.PubMed
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.PubMed
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.PubMed
122.
Schieppati A, Remuzzi G. The future of renoprotection: frustration and promises. Kidney Int. 2003;64(6):1947–55. English.PubMed
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.PubMed
124.
Hall JE. The kidney, hypertension, and obesity. Hypertension. 2003;41(3):625–33. English.PubMed
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.PubMed
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.PubMedCentralPubMed
127.
Wolf G, Ziyadeh FN. Leptin and renal fibrosis. Contrib Nephrol. 2006;151:175–83. English.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
144.
Freedman MR, King J, Kennedy E. Popular diets: a scientific review—executive summary. Obes Res. 2001;9:1S–40S. English.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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. PubMedCentralPubMed
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.PubMed
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.PubMedCentralPubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.
Metadata
Title
The Impacts of Obesity on the Cardiovascular and Renal Systems: Cascade of Events and Therapeutic Approaches
Authors
Zohreh Soltani
Vaughn Washco
Stephen Morse
Efrain Reisin
Publication date
01-02-2015
Publisher
Springer US
Published in
Current Hypertension Reports / Issue 2/2015
Print ISSN: 1522-6417
Electronic ISSN: 1534-3111
DOI
https://doi.org/10.1007/s11906-014-0520-2

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