Abstract
Left ventricular hypertrophy (LVH) and diastolic dysfunction (CHF-D) are the early manifestations of cardiovascular target organ damage in patients with arterial hypertension and signify hypertensive heart disease. Identification of hypertensive heart disease is critical, as these individuals are more prone to congestive heart failure, arrhythmias, myocardial infarction and sudden cardiac death. Regression of left ventricular (LV) mass with antihypertensive therapy decreases the risk of future cardiovascular events. The goal of antihypertensive therapy is to both lower blood pressure (BP) and interrupt BP-independent pathophysiologic processes that promote LVH and CHF-D. The purpose of this review is to summarize current and emerging approaches to the pathophysiology and treatment of hypertensive heart disease.
Similar content being viewed by others
Article PDF
References
Levy D, Anderson KM, Savage D, Kannel WB, Christiansen JC, Castelli WP : Echocardiographically detected left ventricular hypertrophy: prevalence and risk factors. The Framingham heart study. Ann Int Med 1988; 108: 7–13.
Casale PN, Devereux RB, Milner M, et al: Value of echocardiographic measurement of left ventricular mass in predicting cardiovascular morbid events in hypertensive men. Ann Intern Med 1986; 105: 173–178.
Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP : Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990; 322: 1561–1566.
Bikkina M, Larson MG, Levy D : Asymptomatic ventricular arrhythmias and mortality risk in subjects with left ventricular hypertrophy. J Am Coll Cardiol 1993; 22: 1111–1116.
Klingbeil AU, Schneider M, Martus P, Messerli FH, Schmieder RE : A meta-analysis of the effects of treatment on left ventricular mass in essential hypertension. Am J Med 2003; 115: 41–46.
Choi DJ, Koch WJ, Hunter JJ, Rockman HA : Mechanism of beta-adrenergic receptor desensitization in cardiac hypertrophy is increased beta-adrenergic receptor kinase. J Biol Chem 1997; 272: 17223–17229.
Drazner MH, Rame JE, Marino EK, et al: Increased left ventricular mass is a risk factor for the development of a depressed left ventricular ejection fraction within five years: the Cardiovascular Health Study. J Am Coll Cardiol 2004; 43: 2207–2215.
Cooper RS, Simmons BE, Castaner A, Santhanam V, Ghali J, Mar M : Left ventricular hypertrophy is associated with worse survival independent of ventricular function and number of coronary arteries severely narrowed. Am J Cardiol 1990; 65: 441–445.
Ghali JK, Liao Y, Simmons B, Castaner A, Cao G, Cooper RS : The prognostic role of left ventricular hypertrophy in patients with or without coronary artery disease. Ann Intern Med 1992; 117: 831–836.
Deschepper CF, Boutin-Ganache I, Zahabi A, Jiang Z : In search of cardiovascular candidate genes: interactions between phenotypes and genotypes. Hypertension 2002; 39: 332–336.
Molkentin JD, Lu JR, Antos CL, et al: A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell 1998; 93: 215–228.
Hsueh WA, Law RE, Do YS : Integrins, adhesion, and cardiac remodeling. Hypertension 1998; 31: 176–180.
Schunkert H, Jahn L, Izumo S, Apstein CS, Lorell BH : Localization and regulation of c-fos and c-jun protooncogene induction by systolic wall stress in normal and hypertrophied rat hearts. Proc Natl Acad Sci U S A 1991; 88: 11480–11484.
Molkentin JD : Calcineurin-NFAT signaling regulates the cardiac hypertrophic response in coordination with the MAPKs. Cardiovasc Res 2004; 63: 467–475.
Chen MS, Xu FP, Wang YZ, et al: Statins initiated after hypertrophy inhibit oxidative stress and prevent heart failure in rats with aortic stenosis. J Mol Cell Cardiol 2004; 37: 889–896.
Li YY, McTiernan CF, Feldman AM : Interplay of matrix metalloproteinases, tissue inhibitors of metalloproteinases and their regulators in cardiac matrix remodeling. Cardiovasc Res 2000; 46: 214–224.
Polyakova V, Hein S, Kostin S, Ziegelhoeffer T, Schaper J : Matrix metalloproteinases and their tissue inhibitors in pressure-overloaded human myocardium during heart failure progression. J Am Coll Cardiol 2004; 44: 1609–1618.
Sundstrom J, Evans JC, Benjamin EJ, et al: Relations of plasma total TIMP-1 levels to cardiovascular risk factors and echocardiographic measures: the Framingham heart study. Eur Heart J 2004; 25: 1509–1516.
Lindsay MM, Maxwell P, Dunn FG : TIMP-1: a marker of left ventricular diastolic dysfunction and fibrosis in hypertension. Hypertension 2002; 40: 136–141.
Tayebjee MH, Nadar SK, MacFadyen RJ, Lip GY : Tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9 levels in patients with hypertension. Relationship to tissue Doppler indices of diastolic relaxation. Am J Hypertens 2004; 17: 770–774.
Schmieder RE, Martus P, Klingbeil A : Reversal of left ventricular hypertrophy in essential hypertension. A meta-analysis of randomized double-blind studies. JAMA 1996; 275: 1507–1513.
Muiesan ML, Salvetti M, Rizzoni D, et al: Association of change in left ventricular mass with prognosis during long-term antihypertensive treatment. J Hypertens 1995; 13: 1091–1095.
Bromberg JE, Rinkel GJ, Algra A, Limburg M, van Gijn J : Outcome in familial subarachnoid hemorrhage. Stroke 1995; 26: 961–963.
Koren MJ, Ulin RJ, Koren AT, Laragh JH, Devereux RB : Left ventricular mass change during treatment and outcome in patients with essential hypertension. Am J Hypertens 2002; 15: 1021–1028.
Schussheim AE, Diamond JA, Phillips RA : Left ventricular midwall function improves with antihypertensive therapy and regression of left ventricular hypertrophy in patients with asymptomatic hypertension. Am J Cardiol 2001; 87: 61–65.
Sen S, Tarazi RC, Khairallah PA, Bumpus FM : Cardiac hypertrophy in spontaneously hypertensive rats. Circ Res 1974; 35: 775–781.
Dahlof B, Pennert K, Hansson L : Reversal of left ventricular hypertrophy in hypertensive patients. A metaanalysis of 109 treatment studies. Am J Hypertens 1992; 5: 95–110.
Neaton JD, Grimm RH Jr, Prineas RJ, et al: Treatment of mild hypertension study: final results. JAMA 1993; 270: 713–724.
Brilla CG, Funck RC, Rupp H : Lisinopril-mediated regression of myocardial fibrosis in patients with hypertensive heart disease. Circulation 2000; 102: 1388–1393.
Gottdiener JS, Reda DJ, Massie BM, Materson BJ, Williams DW, Anderson RJ : Effect of single-drug therapy on reduction of left ventricular mass in mild to moderate hypertension: comparison of six antihypertensive agents. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. Circulation 1997; 95: 2007–2014.
Lonn E, Shaikholeslami R, Yi Q, et al: Effects of ramipril on left ventricular mass and function in cardiovascular patients with controlled blood pressure and with preserved left ventricular ejection fraction: a substudy of the Heart Outcomes Prevention Evaluation (HOPE) Trial. J Am Coll Cardiol 2004; 43: 2200–2206.
Dahlof B, Devereux RB, Kjeldsen SE, et al: Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002; 359: 995–1003.
Devereux RB, Dahlof B, Gerdts E, et al: Regression of hypertensive left ventricular hypertrophy by losartan compared with atenolol: the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) trial. Circulation 2004; 110: 1456–1462.
Okin PM, Devereux RB, Jern S, et al: Regression of electrocardiographic left ventricular hypertrophy during antihypertensive treatment and the prediction of major cardiovascular events. JAMA 2004; 292: 2343–2349.
Devereux RB, Wachtell K, Gerdts E, et al: Prognostic significance of left ventricular mass change during treatment of hypertension. JAMA 2004; 292: 2350–2356.
ALLHAT Officers and Coordinators for ALLHAT Collaborative Research Group: Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288: 2981–2997.
Zou Y, Yamazaki T, Nakagawa K, et al: Continuous blockade of L-type Ca2+ channels suppresses activation of calcineurin and development of cardiac hypertrophy in spontaneously hypertensive rats. Hypertens Res 2002; 25: 117–124.
Kupari M, Hautanen A, Lankinen L, et al: Associations between human aldosterone synthase (CYP11B2) gene polymorphisms and left ventricular size, mass, and function. Circulation 1998; 97: 569–575.
Stella P, Bigatti G, Tizzoni L, et al: Association between aldosterone synthase (CYP11B2) polymorphism and left ventricular mass in human essential hypertension. J Am Coll Cardiol 2004; 43: 265–270.
Weber KT, Brilla CG : Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system. Circulation 1991; 83: 1849–1865.
Pitt B, Reichek N, Willenbrock R, et al: Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. Circulation 2003; 108: 1831–1838.
Sato A, Hayashi M, Saruta T : Relative long-term effects of spironolactone in conjunction with an angiotensin-converting enzyme inhibitor on left ventricular mass and diastolic function in patients with essential hypertension. Hypertens Res 2002; 25: 837–842.
Wilkins BJ, Dai YS, Bueno OF, et al: Calcineurin/NFAT coupling participates in pathological, but not physiological, cardiac hypertrophy. Circ Res 2004; 94: 110–118.
Sussman MA, Lim HW, Gude N, et al: Prevention of cardiac hypertrophy in mice by calcineurin inhibition. Science 1998; 281: 1690–1693.
Yang G, Meguro T, Hong C, et al: Cyclosporine reduces left ventricular mass with chronic aortic banding in mice, which could be due to apoptosis and fibrosis. J Mol Cell Cardiol 2001; 33: 1505–1514.
Nagata K, Somura F, Obata K, et al: AT1 receptor blockade reduces cardiac calcineurin activity in hypertensive rats. Hypertension 2002; 40: 168–174.
Varo N, Iraburu MJ, Varela M, López B, Etayo JC, DÃez J : Chronic AT1 blockade stimulates extracellular collagen type I degradation and reverses myocardial fibrosis in spontaneously hypertensive rats. Hypertension 2000; 35: 1197–1202.
Li H, Simon H, Bocan TM, Peterson JT : MMP/TIMP expression in spontaneously hypertensive heart failure rats: the effect of ACE- and MMP-inhibition. Cardiovasc Res 2000; 46: 298–306.
Suzuki J, Iwai M, Nakagami H, et al: Role of angiotensin II-regulated apoptosis through distinct AT1 and AT2 receptors in neointimal formation. Circulation 2002; 106: 847–853.
Mukawa H, Toki Y, Miyazaki Y, Matsui H, Okumura K, Ito T : Angiotensin II type 2 receptor blockade partially negates antihypertrophic effects of type 1 receptor blockade on pressure-overload rat cardiac hypertrophy. Hypertens Res 2003; 26: 89–95.
Collins AR, Schnee J, Wang W, et al: Osteopontin modulates angiotensin II-induced fibrosis in the intact murine heart. J Am Coll Cardiol 2004; 43: 1698–1705.
Matsui Y, Jia N, Okamoto H, et al: Role of osteopontin in cardiac fibrosis and remodeling in angiotensin II-induced cardiac hypertrophy. Hypertension 2004; 43: 1195–1201.
Takahashi N, Saito Y, Kuwahara K, et al: Angiotensin II-induced ventricular hypertrophy and extracellular signal-regulated kinase activation are suppressed in mice overexpressing brain natriuretic peptide in circulation. Hypertens Res 2003; 26: 847–853.
Suzuki M, Hamada M, Yamamoto K, Kazatani Y, Hiwada K : Brain natriuretic peptide as a risk marker for incident hypertensive cardiovascular events. Hypertens Res 2002; 25: 669–676.
Vanderheyden M, Goethals M, Verstreken S, et al: Wall stress modulates brain natriuretic peptide production in pressure overload cardiomyopathy. J Am Coll Cardiol 2004; 44: 2349–2354.
Uusimaa P, Tokola H, Ylitalo A, et al: Plasma B-type natriuretic peptide reflects left ventricular hypertrophy and diastolic function in hypertension. Int J Cardiol 2004; 97: 251–256.
Nakamura M, Tanaka F, Yonezawa S, Satou K, Nagano M, Hiramori K : The limited value of plasma B-type natriuretic peptide for screening for left ventricular hypertrophy among hypertensive patients. Am J Hypertens 2003; 16: 1025–1029.
Maki T, Nasa Y, Tanonaka K, Takahashi M, Takeo S : Direct inhibition of neutral endopeptidase in vasopeptidase inhibitor-mediated amelioration of cardiac remodeling in rats with chronic heart failure. Mol Cell Biochem 2003; 254: 265–273.
Graham D, Hamilton C, Beattie E, Spiers A, Dominiczak AF : Comparison of the effects of omapatrilat and irbesartan/hydrochlorothiazide on endothelial function and cardiac hypertrophy in the stroke-prone spontaneously hypertensive rat: sex differences. J Hypertens 2004; 22: 329–337.
Indolfi C, Di Lorenzo E, Perrino C, et al: Hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin prevents cardiac hypertrophy induced by pressure overload and inhibits p21ras activation. Circulation 2002; 106: 2118–2124.
Shioi T, McMullen JR, Tarnavski O, et al: Rapamycin attenuates load-induced cardiac hypertrophy in mice. Circulation 2003; 107: 1664–1670.
Glueck SB, Dzau VJ : Physiological genomics: implications in hypertension research. Hypertension 2002; 39: 310–315.
Kimura B, Mohuczy D, Tang X, Phillips MI : Attenuation of hypertension and heart hypertrophy by adeno-associated virus delivering angiotensinogen antisense. Hypertension 2001; 37: 376–380.
Pachori AS, Numan MT, Ferrario CM, Diz DM, Raizada MK, Katovich MJ : Blood pressure-independent attenuation of cardiac hypertrophy by AT1R-AS gene therapy. Hypertension 2002; 39: 969–975.
Metcalfe BL, Huentelman MJ, Parilak LD, et al: Prevention of cardiac hypertrophy by angiotensin II type-2 receptor gene transfer. Hypertension 2004; 43: 1233–1238.
Jones RC, Francis GS, Lauer MS : Predictors of mortality in patients with heart failure and preserved systolic function in the Digitalis Investigation Group trial. J Am Coll Cardiol 2004; 44: 1025–1029.
Gonzalez-Fernandez RB, Altieri PI, Diaz LM, et al: Effects of enalapril on heart failure in hypertensive patients with diastolic dysfunction. Am J Hypertens 1992; 5: 480–483.
Aronow WS, Kronzon I : Effect of enalapril on congestive heart failure treated with diuretics in elderly patients with prior myocardial infarction and normal left ventricular ejection fraction. Am J Cardiol 1993; 71: 602–604.
Brilla CG, Funck RC, Rupp H : Lisinopril-mediated regression of myocardial fibrosis in patients with hypertensive heart disease. Circulation 2000; 102: 1388–1393.
Yusuf S, Pfeffer MA, Swedberg K, et al: Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet 2003; 362: 777–781.
Grandi AM, Imperiale D, Santillo R, et al: Aldosterone antagonist improves diastolic function in essential hypertension. Hypertension 2002; 40: 647–652.
Mottram PM, Haluska B, Leano R, Cowley D, Stowasser M, Marwick TH : Effect of aldosterone antagonism on myocardial dysfunction in hypertensive patients with diastolic heart failure. Circulation 2004; 110: 558–565.
Setaro JF, Zaret BL, Schulman DS, Black HR, Soufer R : Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic filling and normal left ventricular systolic performance. Am J Cardiol 1990; 66: 981–986.
Given BD, Lee TH, Stone PH, Dzau VJ : Nifedipine in severely hypertensive patients with congestive heart failure and preserved ventricular systolic function. Arch Intern Med 1985; 145: 281–285.
Hung MJ, Cherng WJ, Kuo LT, Wang CH : Effect of verapamil in elderly patients with left ventricular diastolic dysfunction as a cause of congestive heart failure. Int J Clin Pract 2002; 56: 57–62.
Andersson B, Caidahl K, di Lenarda A, et al: Changes in early and late diastolic filling patterns induced by long-term adrenergic beta-blockade in patients with idiopathic dilated cardiomyopathy. Circulation 1996; 94: 673–682.
Nodari S, Metra M, Dei CL : Beta-blocker treatment of patients with diastolic heart failure and arterial hypertension. A prospective, randomized, comparison of the long-term effects of atenolol vs. nebivolol. Eur J Heart Fail 2003; 5: 621–627.
Bonow RO, Udelson JE : Left ventricular diastolic dysfunction as a cause of congestive heart failure: mechanisms and management. Ann Intern Med 1992; 117: 502–510.
Gaasch WH : Diagnosis and treatment of heart failure based on left ventricular systolic or diastolic dysfunction. JAMA 1994; 271: 1276–1280.
Packer M : Abnormalities of diastolic function as a potential cause of exercise intolerance in chronic heart failure. Circulation 1990; 81 ( 2 Suppl): III78–III86.
Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure: The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med 1993; 153: 154–183.
Lorell BH, Isoyama S, Grice WN, Weinberg EO, Apstein CS : Effects of ouabain and isoproterenol on left ventricular diastolic function during low-flow ischemia in isolated, blood- perfused rabbit hearts. Circ Res 1988; 63: 457–467.
The effect of digoxin on mortality and morbidity in patients with heart failure. The Digitalis Investigation Group. N Engl J Med 1997; 336: 525–533.
Gandhi SK, Powers JC, Nomeir AM, et al: The pathogenesis of acute pulmonary edema associated with hypertension. N Engl J Med 2001; 344: 17–22.
Brutsaert DL, Sys SU, Gillebert TC : Diastolic failure: pathophysiology and therapeutic implications. J Am Coll Cardiol 1993; 22: 318–325 [ published erratum appears in J Am Coll Cardiol 1993; 22: 1272].
Chobanian AV, Bakris GL, Black HR, et al: The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289: 2560–2571.
Kuwahara F, Kai H, Tokuda K, et al: Hypertensive myocardial fibrosis and diastolic dysfunction: another model of inflammation? Hypertension 2004; 43: 739–745.
Matsumoto T, Wada A, Tsutamoto T, Ohnishi M, Isono T, Kinoshita M : Chymase inhibition prevents cardiac fibrosis and improves diastolic dysfunction in the progression of heart failure. Circulation 2003; 107: 2555–2558.
Ogata T, Miyauchi T, Sakai S, Takanashi M, Irukayama-Tomobe Y, Yamaguchi I : Myocardial fibrosis and diastolic dysfunction in deoxycorticosterone acetate-salt hypertensive rats is ameliorated by the peroxisome proliferator-activated receptor-alpha activator fenofibrate, partly by suppressing inflammatory responses associated with the nuclear factor-kappa-B pathway. J Am Coll Cardiol 2004; 43: 1481–1488.
Lenfant C, Chobanian AV, Jones DW, Roccella EJ : Seventh report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). Resetting the Hypertension Sails. Hypertension 2003; 41: 1178–1179.
Schunkert H, Hense H-W, Holmer SR, et al: Association between a deletion polymorphism of the angiotensin converting-enzyme gene and left ventricular hypertrophy. N Engl J Med 1994; 330: 1634–1638.
Perticone F, Ceravolo R, Cosco C, et al: Deletion polymorphism of angiotensin-converting enzyme gene and left ventricular hypertrophy in southern Italian patients. J Am Coll Cardiol 1997; 29: 365–369.
Gharavi AG, Lipkowitz MS, Diamond JA, Jhang JS, Phillips RA : Deletion polymorphism of the angiotensin-converting enzyme gene is independently associated with left ventricular mass and geometric remodeling in systemic hypertension. Am J Cardiol 1996; 77: 1315–1319.
Alfakih K, Maqbool A, Sivananthan M, et al: Left ventricle mass index and the common, functional, X-linked angiotensin II type-2 receptor gene polymorphism (-1332 G/A) in patients with systemic hypertension. Hypertension 2004; 43: 1189–1194.
Tang W, Devereux RB, Rao DC, et al: Associations between angiotensinogen gene variants and left ventricular mass and function in the HyperGEN study. Am Heart J 2002; 143: 854–860.
Poch E, Gonzalez D, Gomez-Angelats E, et al: G-protein beta(3) subunit gene variant and left ventricular hypertrophy in essential hypertension. Hypertension 2000; 35: 214–218.
Obineche EN, Frossard PM, Bokhari AM : An association study of five genetic loci and left ventricular hypertrophy amongst Gulf Arabs. Hypertens Res 2001; 24: 635–639.
Nakayama T, Soma M, Takahashi Y, Rehemudula D, Kanmatsuse K, Furuya K : Functional deletion mutation of the 5′-flanking region of type A human natriuretic peptide receptor gene and its association with essential hypertension and left ventricular hypertrophy in the Japanese. Circ Res 2000; 86: 841–845.
Arnett DK, Devereux RB, Kitzman D, et al: Linkage of left ventricular contractility to chromosome 11 in humans: the HyperGEN Study. Hypertension 2001; 38: 767–772.
Akhter SA, Milano CA, Shotwell KF, et al: Transgenic mice with cardiac overexpression of alpha1-adrenergic In vivo alpha1-adrenergic receptor-mediated regulation of beta-adrenergic signaling. J Biol Chem 1997; 272: 21253–21259.
Tang W, Arnett DK, Devereux RB, Atwood LD, Kitzman DW, Rao DC : Linkage of left ventricular early diastolic peak filling velocity to chromosome 5 in hypertensive African Americans: the HyperGEN echocardiography study. Am J Hypertens 2002; 15: 621–627.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Diamond, J., Phillips, R. Hypertensive Heart Disease. Hypertens Res 28, 191–202 (2005). https://doi.org/10.1291/hypres.28.191
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1291/hypres.28.191
Keywords
This article is cited by
-
2023 update and perspectives
Hypertension Research (2023)
-
Clinicopathological characteristics and outcomes of anti-neutrophil cytoplasmic autoantibody-related renal vasculitis with hyperuricemia: a retrospective case-control study
Scientific Reports (2021)
-
Left atrial, ventricular and atrio-ventricular strain in patients with subclinical heart dysfunction
The International Journal of Cardiovascular Imaging (2019)
-
Modelling Cardiac Tissue Growth and Remodelling
Journal of Elasticity (2017)
-
Effects of renal sympathetic denervation and angiotensin-converting enzyme inhibitor on left ventricular hypertrophy
Herz (2015)