Hypertensive Heart Disease and Obesity: A Complex Interaction Between Hemodynamic and Not Hemodynamic Factors

  • Riccardo Sarzani
  • Marica Bordicchia
  • Francesco Spannella
  • Paolo Dessì-Fulgheri
  • Massimiliano Fedecostante
Review Article


The worldwide prevalence of obesity has nearly doubled, with an increase in obesity-related cardiovascular disease and mortality. Several factors are involved in the genesis of hypertension and hypertensive heart disease (HHD) in overweight/obesity. This review is focused on bridging factors between excessive adiposity and HHD, presenting a unifying hypothesis of vascular–metabolic syndrome, where an “handicap” of the natriuretic peptide system has a central role both in adipocyte dysmetabolism as well as in increased blood pressure and HHD.


Obesity Adipocyte Hypertensive heart disease Cardiovascular risk Natriuretic peptides 


  1. 1.
    World health statistics 2013. World Health Organization; 2013.Google Scholar
  2. 2.
    Finkelstein EA, Trogdon JG, Cohen JW, Dietz W. Annual medical spending attributable to obesity: payer-and service-specific estimates. Health Aff. 2009;28:w822–31.CrossRefGoogle Scholar
  3. 3.
    Gallus S, Odone A, Lugo A, Bosetti C, Colombo P, Zuccaro P, La Vecchia C. Overweight and obesity prevalence and determinants in Italy: an update to 2010. Eur J Nutr. 2013;52(2):677–85.PubMedCrossRefGoogle Scholar
  4. 4.
    Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002;287(3):356–9.PubMedCrossRefGoogle Scholar
  5. 5.
    The Italian Cardiovascular Epidemiological Observatory. It Heart J. 2004; (suppl 3):49S–52S.Google Scholar
  6. 6.
    Stamler J, Dyer AR, Shekelle RB, Neaton J, Stamler R. Relationship of baseline major risk factors to coronary and all-cause mortality, and to longevity: findings from long-term follow-up of Chicago cohorts. Cardiology. 1993;82:191–222.PubMedCrossRefGoogle Scholar
  7. 7.
    l’Allemand-Jander D. Clinical diagnosis of metabolic and cardiovascular risks in overweight children: early development of chronic diseases in the obese child. Int J Obes (Lond). 2010;34(suppl 2):S32–6.CrossRefGoogle Scholar
  8. 8.
    Juonala M, Magnussen CG, Berenson GS, Venn A, Burns TL, Sabin MA, Srinivasan SR, Daniels SR, Davis PH, Chen W, Sun C, Cheung M, Viikari JS, Dwyer T, Raitakari OT. Childhood adiposity, adult adiposity, and cardiovascular risk factors. N Engl J Med. 2011;365:1876–85.PubMedCrossRefGoogle Scholar
  9. 9.
    Bramlage P, Pittrow D, Wittchen HU, Kirch W, Boehler S, Lehnert H, Hoefler M, Unger T, Sharma AM. Hypertension in overweight and obese primary care patients is highly prevalent and poorly controlled. Am J Hypertens. 2004;17:904–10.PubMedCrossRefGoogle Scholar
  10. 10.
    Hansen TW, Li Y, Boggia J, Thijs L, Richart T, Staessen JA. Predictive role of the night-time blood pressure. Hypertension. 2011;57:3–10.PubMedCrossRefGoogle Scholar
  11. 11.
    Kotsis V, Stabouli S, Bouldin M, Low A, Toumanidis S, Zakopoulos N. Impact of obesity on 24-hour ambulatory blood pressure and hypertension. Hypertension. 2005;45:602–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Mokhlesi B. Obesity hypoventilation syndrome: a state-of-the-art review. Resp Care. 2010;55:1347–62.Google Scholar
  13. 13.
    The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). ESH/ESC Guidelines for the management of arterial hypertension. J Hypertens. 2013;2013(31):1281–357.Google Scholar
  14. 14.
    Aucott L, Rothnie H, McIntyre L, Thapa M, Waweru C, Gray D. Long-term weight loss from lifestyle intervention benefits blood pressure? A systematic review. Hypertension. 2009;54:756–62.PubMedCrossRefGoogle Scholar
  15. 15.
    Siebenhofer A, Jeitler K, Berghold A, Waltering A, Hemkens LG, Semlitsch T, Pachler C, Strametz R, Horvath K. Long-term effects of weight-reducing diets in hypertensive patients. Cochrane Database Syst Rev. 2011;7(9):CD008274.Google Scholar
  16. 16.
    Lewington S, Clarke R, Qiziibash N, Peto R, Collins R, Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903–13.PubMedCrossRefGoogle Scholar
  17. 17.
    Gleiberman L. Blood pressure and dietary salt in human populations. Ecol Food Nutr. 1973;2:143–56.CrossRefGoogle Scholar
  18. 18.
    Dyer AR, Elliott P, Marmot M, Kesteloot H, Stamler R, Stamler J. Commentary: strength and importance of the relation of dietary salt to blood pressure. Intersalt Steering and Editorial Committee. BMJ. 1996;29(312):1661–4.CrossRefGoogle Scholar
  19. 19.
    Donfrancesco C, Ippolito R, Lo Noce C, Palmieri L, Iacone R, Russo O, Vanuzzo D, Galletti F, Galeone D, Giampaoli S, Strazzullo P. Excess dietary sodium and inadequate potassium intake in Italy: results of the MINISAL study. Nutr Metab Cardiovasc Dis. 2013;23:850–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Rocchini AP, Key J, Bondie D, Chico R, Moorehead C, Katch V, Martin M. The effect of weight loss on the sensitivity of blood pressure to sodium in obese adolescents. N Engl J Med. 1989;321:580–5.PubMedCrossRefGoogle Scholar
  21. 21.
    Oliver WJ, Cohen EL, Neel JV. Blood pressure, sodium intake, and sodium related hormones in the Yanomamo Indians, a “no-salt” culture. Circulation. 1975;52:146–51.PubMedCrossRefGoogle Scholar
  22. 22.
    Pratt JH. Central role for ENaC in development of hypertension. J Am Soc Nephrol. 2005;16:3154–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Sarzani R, Guerra F, Mancinelli L, Buglioni A, Franchi E, Dessì-Fulgheri P. Plasma aldosterone is increased in class 2 and 3 obese essential hypertensive patients despite drug treatment. Am J Hypertens. 2012;25:818–26.PubMedCrossRefGoogle Scholar
  24. 24.
    Díez J, Frohlich ED. A translational approach to hypertensive heart disease. Hypertension. 2010;55:1–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Weber KT, Brilla CG, Janicki JS. Myocardial fibrosis: functional significance and regulatory factors. Cardiovasc Res. 1993;27:341–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Schwartzkopff B, Motz W, Frenzel H, Vogt M, Knauer S, Strauer BE. Structural and functional alterations of the intramyocardial coronary arterioles in patients with arterial hypertension. Circulation. 1993;88:993–1003.PubMedCrossRefGoogle Scholar
  27. 27.
    Boldt A, Wetzel U, Lauschke J, Weigl J, Gummert J, Hindricks G, Kottkamp H, Dhein S. Fibrosis in left atrial tissue of patients with atrial fibrillation with and without underlying mitral valve disease. Heart. 2004;90:400–5.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    De Simone G, Devereux RB, Chinali M, Roman MJ, Lee ET, Resnick HE, Howard BV. Metabolic syndrome and left ventricular hypertrophy in the prediction of cardiovascular events: the Strong Heart Study. Nutr Metab Cardiovasc Dis. 2009;19:98–104.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Bauersachs J, Bouloumie A, Fraccarollo D, Hu K, Busse R, Ertl G. Endothelial dysfunction in chronic myocardial infarction despite increased vascular endothelial nitric oxide synthase and soluble guanylate cyclase expression: role of enhanced vascular superoxide production. Circulation. 1999;100:292–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Yokoyama T, Nakano M, Bednarczyk JL, McIntyre BW, Entman M, Mann DL. Tumor necrosis factor-alpha provokes a hypertrophic growth response in adult cardiac myocytes. Circulation. 1997;95:1247–52.PubMedCrossRefGoogle Scholar
  31. 31.
    Lim JY, Prk SJ, Hwang HY, Park EJ, Nam JH, Kim J, Park SI. TGF-beta1 induces cardiac hypertrophic responses via PKC-dependent ATF-2 activation. J Mol Cell Cardiol. 2005;39:627–36.PubMedCrossRefGoogle Scholar
  32. 32.
    Kuwahara F, Kai H, Tokuda K, Takeya M, Takeshita A, Egashira K, Imaizumi T. Hypertensive myocardial fibrosis and diastolic dysfunction: another model of inflammation? Hypertension. 2004;43:739–45.PubMedCrossRefGoogle Scholar
  33. 33.
    Sciarretta S, Ferrucci A, Ciavarella GM, De Paolis P, Venturelli V, Tocci G, De Biase L, Rubattu S, Volpe M. Markers of inflammation and fibrosis are related to cardiovascular damage in hypertensive patients with metabolic syndrome. Am J Hypertens. 2007;20:784–91.PubMedCrossRefGoogle Scholar
  34. 34.
    Guerra F, Mancinelli L, Angelini L, Fortunati M, Rappelli A, Dessì-Fulgheri P, Sarzani R. The association of left ventricular hypertrophy with metabolic syndrome is dependent on body mass index in hypertensive overweight or obese patients. PLoS ONE. 2011;6(1):e16630.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Sarzani R, Salvi F, Dessì-Fulgheri P, Rappelli A. Renin–angiotensin system, natriuretic peptides, obesity, metabolic syndrome, and hypertension: an integrated view in humans. J Hypertens. 2008;26:831–43.PubMedCrossRefGoogle Scholar
  36. 36.
    Dluhy RG, Williams GH. Aldosterone—villain or bystander? N Engl J Med. 2004;351:8–10.PubMedCrossRefGoogle Scholar
  37. 37.
    Brilla CG, Rupp H, Funck R, Maisch B. The renin–angiotensin–aldosterone system and myocardial collagen matrix remodelling in congestive heart failure. Eur Heart J. 1995;16 Suppl O:107–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Sarzani R, Brecher P, Chobanian AV. Growth factor expression in aorta of normotensive and hypertensive rats. J Clin Invest. 1989;83:1404–8.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Takasaki I, Chobanian AV, Sarzani R, Brecher P. Effect of hypertension on fibronectin expression in the rat aorta. J Biol Chem. 1990;265:21935–9.PubMedGoogle Scholar
  40. 40.
    Sarzani R, Arnaldi G, Chobanian AV. Hypertension-induced changes of platelet-derived growth factor receptor expression in rat aorta and heart. Hypertension. 1991;17:888–95.PubMedCrossRefGoogle Scholar
  41. 41.
    Sarzani R, Arnaldi G, Takasaki I, Brecher P, Chobanian AV. Effects of hypertension and aging on platelet-derived growth factor and platelet-derived growth factor receptor expression in rat aorta and heart. Hypertension. 1991;18:III93–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Glenn DJ, Wang F, Nishimoto M, Cruz MC, Uchida Y, Holleran WM, Zhang Y, Yeghiazarians Y, Gardner DG. A murine model of isolated cardiac steatosis leads to cardiomyopathy. Hypertension. 2011;57:216–22.PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Sarzani R. The clinical significance of metabolic syndrome in hypertension: metabolic syndrome increases cardiovascular risk: the contrary position. High Blood Press Cardiovasc Prev. 2008;15:59–62.PubMedCrossRefGoogle Scholar
  44. 44.
    Maack T, Suzuki M, Almeida FA, Nussenzveig D, Scarborough RM, McEnroe GA, Lewicki JA. Physiological role of silent receptors of atrial natriuretic factor. Science. 1987;238:675–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Sarzani R, Paci VM, Dessi-Fulgheri P, Espinosa E, Rappelli A. Comparative analysis of atrial natriuretic peptide receptor expression in rat tissues. J Hypertens Suppl. 1993;11(5):S214–5.PubMedCrossRefGoogle Scholar
  46. 46.
    Sarzani R, Dessì-Fulgheri P, Paci VM, Espinosa E, Rappelli A. Expression of natriuretic peptide receptors in human adipose and other tissues. J Endocrinol Invest. 1996;19:581–5.PubMedCrossRefGoogle Scholar
  47. 47.
    Sarzani R, Paci VM, Zingaretti CM, Pierleoni C, Cinti S, Cola G, Rappelli A, Dessì-Fulgheri P. Fasting inhibits natriuretic peptides clearance receptor expression in rat adipose tissue. J Hypertens. 1995;13:1241–6.PubMedCrossRefGoogle Scholar
  48. 48.
    Nakatsuji H, Maeda N, Hibuse T, Hiuge A, Hirata A, Kuroda Y, Kishida K, Kihara S, Funahashi T, Shimomura I. Reciprocal regulation of natriuretic peptide receptors by insulin in adipose cells. Biochem Biophys Res Commun. 2010;392:100–5.PubMedCrossRefGoogle Scholar
  49. 49.
    Dessi-Fulgheri P, Sarzani R, Tamburrini P, Moraca A, Espinosa E, Cola G, Giantomassi L, Rappelli A. Plasma atrial natriuretic peptide and natriuretic peptide receptor gene expression in adipose tissue of normotensive and hypertensive obese patients. J Hypertens. 1997;15:1695–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Dessì-Fulgheri P, Sarzani R, Serenelli M, Tamburrini P, Spagnolo D, Giantomassi L, Espinosa E, Rappelli A. Low caloric diet enhances renal, hemodynamic, and humoral effects of exogenous atrial natriuretic peptide in obese hypertensives. Hypertension. 1999;33:658–62.PubMedCrossRefGoogle Scholar
  51. 51.
    Wang TJ, Larson MG, Keyes MJ, Levy D, Benjamin EL, Vasan RS. Association of plasma natriuretic peptide levels with metabolic risk factors in ambulatory individuals. Circulation. 2007;115:1345–53.PubMedCrossRefGoogle Scholar
  52. 52.
    Savoia C, Volpe M, Alonzo A, Rossi C, Rubattu S. Natriuretic peptides and cardiovascular damage in the metabolic syndrome: molecular mechanisms and clinical implications. Clin Sci. 2010;118:231–40.CrossRefGoogle Scholar
  53. 53.
    Rubattu S, Sciarretta S, Morriello A, Calvieri C, Battistoni A, Volpe M. NPR-C: a component of the natriuretic peptide family with implications in human diseases. J Mol Med. 2010;88:889–97.PubMedCrossRefGoogle Scholar
  54. 54.
    Matsukawa N, Grzesik WJ, Takahashi N, Pandey KN, Pang S, Yamauchi M, Smithies O. The natriuretic peptide clearance receptor locally modulates the physiological effects of the natriuretic peptide system. Proc Natl Acad Sci. 1999;96:7403–8.PubMedCentralPubMedCrossRefGoogle Scholar
  55. 55.
    Tamura N, Ogawa Y, Chusho H, Nakamura K, Nakao K, Suda M, Kasahara M, Hashimoto R, Katsuura G, Mukoyama M, Itoh H, Saito Y, Tanaka I, Otani H, Katsuki H, Nakao K. Cardiac fibrosis in mice lacking brain natriuretic peptide. Proc Natl Acad Sci. 2000;97:4239–44.PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Knowles JW, Esposito G, Mao L, Hagaman JR, Fox JE, Smithies O, Rockman HA, Maeda N. Pressure-independent enhancement of cardiac hypertrophy in natriuretic peptide receptor A-deficient mice. J Clin Invest. 2001;107(8):975–84.PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Bordicchia M, Liu D, Amri EZ, Ailhaud G, Dessì-Fulgheri P, Zhang C, Takahashi N, Sarzani R, Collins S. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. J Clin Invest. 2012;122:1022–36.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Riccardo Sarzani
    • 1
  • Marica Bordicchia
    • 1
  • Francesco Spannella
    • 1
  • Paolo Dessì-Fulgheri
    • 1
  • Massimiliano Fedecostante
    • 1
  1. 1.Internal Medicine and Geriatrics, “Hypertension Excellence Centre” of the European Society of Hypertension, Department of Clinical and Molecular SciencesUniversity “Politecnica delle Marche”, Italian National Research Centre on Aging “U. Sestilli”, IRCCS-INRCAAnconaItaly

Personalised recommendations