Current Cardiology Reports

, Volume 4, Issue 6, pp 449–457 | Cite as

Hypertension, left ventricular hypertrophy, and sudden death

  • Lwin Lwin Tin
  • D. Gareth Beevers
  • Gregory Y. H. Lip
Article

Abstract

Left ventricular hypertrophy (LVH), a form of end-organ damage in hypertension, is associated with increased incidence of sudden cardiac death (SCD). This review explores the possible mechanisms behind this phenomenon. SCD in LVH could be thrombotic/ischemic or arrhythmic (eg, myocardial ischemia, even in the absence of significant coronary artery disease, may be one important factor). Abnormalities of flow-mediated dilatation, endothelial function, and a hypercoagulable state are well-observed abnormalities in association with hypertension and LVH, although their precise contributory role is as yet undefined in the pathogenesis of sudden death. Electrophysiologic abnormalities are also well documented in LVH, and such patients are more predisposed to arrhythmias. In the past decade, many studies have investigated the regression of LVH, and recent studies are addressing whether the latter translates into a prognostic benefit.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Lip GYH, Lydakis C, Zarafis J, Messerli FH: Regression of LVH or improved prognosis (or both): what is the question? J Hum Hypertens 1998, 12:423–425.PubMedCrossRefGoogle Scholar
  2. 2.
    Nicoletti A, Heudes D, Hinglais N, et al.: Left ventricular fibrosis in hypertensive rats. Effect of losartan and spironolactone. Hypertension 1995, 26:101–111.PubMedGoogle Scholar
  3. 3.
    Vogt M, Strauer BE: Systolic ventricular function and heart failure due to coronary microangiopathy in hypertensive disease. Am J Cardiol 1995, 76:48D-53D.PubMedCrossRefGoogle Scholar
  4. 4.
    Liao Y, Cooper RS, McGee DL, et al.: The relative effects of left ventricular hypertrophy, coronary artery disease and left ventricular dysfunction on survival among blacks. JAMA 1995, 273:1592–1597.PubMedCrossRefGoogle Scholar
  5. 5.
    Levy D, Larson MG, Vasan RS, et al.: Progression from hypertension to congestive heart failure. JAMA 1996, 275:1557–1562.PubMedCrossRefGoogle Scholar
  6. 6.
    Kannel WB, Abbott RD: A prognostic comparison of asymptomatic left ventricular hypertrophy and unrecognized myocardial dysfunction: the Framingham Study. Am Heart J 1986, 111:391–397.PubMedCrossRefGoogle Scholar
  7. 7.
    Dunn FG, McLenachan JM, Isles CG, et al.: Left ventricular hypertrophy and mortality in hypertension: an analysis of data from the Glasgow Blood Pressure clinic. J Hypertens 1990, 8:775–782.PubMedCrossRefGoogle Scholar
  8. 8.
    Haider AW, Larson MG, Benjamin EJ, Levy D: Increased left ventricular mass and hypertrophy are associated with increased risk for sudden death. J Am Coll Cardiol 1998, 32:1454–1459.PubMedCrossRefGoogle Scholar
  9. 9.
    Koren MJ, Devereux RB, Casale PN, et al.: Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med 1991, 114:345–352.PubMedGoogle Scholar
  10. 10.
    Vakili BA, Okin PM, Devereux RB: Prognostic implications of left ventricular hypertrophy. Am Heart J 2001, 141:334–341.PubMedCrossRefGoogle Scholar
  11. 11.
    Lip GYH, Felmeden DC, Li-Saw-Hee FC, Beevers DG: Hypertensive heart disease. A complex syndrome or a hypertensive ‘cardiomyopathy’. Eur Heart J 2000, 21:1653–1665. Important recent overview of hypertensive heart disease.PubMedCrossRefGoogle Scholar
  12. 12.
    Levy D, Garrison RJ, Savage DD, et al.: Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990, 322:1561–1566.PubMedCrossRefGoogle Scholar
  13. 13.
    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.PubMedCrossRefGoogle Scholar
  14. 14.
    Parfrey PS, Harnett JD, Griffiths SM, et al.: The clinical course of left ventricular hypertrophy in dialysis patients. Nephron 1990, 55:114–120.PubMedCrossRefGoogle Scholar
  15. 15.
    Ghali JK, Liao Y, Simmons B, et al.: The prognostic role of left ventricular hypertrophy in patients with and without coronary artery disease. Ann Intern Med 1992, 117:831–836.PubMedGoogle Scholar
  16. 16.
    Myerburg RJ, Kessler KM, Castellanos A: Sudden cardiac death. Structure, function and time-dependence of risk. Circulation 1992, 85(Suppl 1):I2-I10.PubMedGoogle Scholar
  17. 17.
    Bigger JT Jr.: Identification of patients at high risk for sudden cardiac death. Am J Cardiol 1984, 54:3D-8D.PubMedCrossRefGoogle Scholar
  18. 18.
    Frank S, Johnson A, Ross J Jr.: Natural history of valvular aortic stenosis. Br Heart J 1973, 35:41.PubMedGoogle Scholar
  19. 19.
    Pedretti R, Etro MD, Laporta L, et al.: Prediction of late arrhythmic events after acute myocardial infarction from combined use of non-invasive prognostic variables and inducibility of sustained monomorphic ventricular tachycardia. Am J Cardiol 1993, 71:1131–1141.PubMedCrossRefGoogle Scholar
  20. 20.
    Bayes de Luna A, Coumel P, Leclercq JF: Ambulatory sudden cardiac death: mechanism of fatal arrhythmia on the basis of data from 157 cases. Am Heart J 1989, 117:151–159.PubMedCrossRefGoogle Scholar
  21. 21.
    Schwartzkopf B, Frentzel H, Dieckerhoff J, et al.: Morphometric investigation of human myocardium in arterial hypertension in arterial hypertension and valvular aortic stenosis. Eur Heart J 1992, 13(suppl D):17–23.Google Scholar
  22. 22.
    Maron BJ, Nichols PF, Pickle LW, et al.: Patterns of inheritance in hypertrophic cardiomyopathy. Assessment by M-mode and two-dimensional echocardiogram. Am J Cardiol 1984, 53:1087–1094.PubMedCrossRefGoogle Scholar
  23. 23.
    Greaves SC, Roche AHG, Neutze JM, et al.: Inheritence of hypertrophic cardiomyopathy: a cross-sectional and M mode echocardiographic study of 50 families. Br Heart J 1987, 58:259–266.PubMedGoogle Scholar
  24. 24.
    Koyanagi S, Eastham C, Marcus M: Effect of chronic hypertension and left ventricular hypertrophy on the incidence of sudden cardiac death after circumflex artery occlusion in conscious dogs. Circulation 1982, 65:1192–1197.PubMedGoogle Scholar
  25. 25.
    Bishop SP, Powell PC, Hasebe N, et al.: Coronary vascular morphology in pressure-overloaded left ventricular hypertrophy. J Mol Cell Cardiol 1996, 28:141–154.PubMedCrossRefGoogle Scholar
  26. 26.
    Tillmans H, Neumann FJ, Parekh N, et al.: Microcirculation in the hypertrophic and ischaemic heart. Eur J Clin Pharm 1990, 39(Suppl 1):S9-S12.CrossRefGoogle Scholar
  27. 27.
    Kingsbury MP, Turner MA, Flores NA, et al.: Endogenous and exogenous coronary vasodilatation are attenuated in cardiac hypertrophy: a morphological effect? J Mol Cell Cardiol 2000, 32:527–538.PubMedCrossRefGoogle Scholar
  28. 28.
    McIntyre H, Fry CH: Abnormal action potential conduction in isolated human hyperyrophied left ventricular myocardium. J Cardiovasc Electrophysiol 1997, 8:887–894.PubMedCrossRefGoogle Scholar
  29. 29.
    Dalton GR, Jones JV, Evans SJ, Levi AJ: Wall stress induced arrhythmias in the working rat heart as LVH regresses during captopril treatment. Cardiovasc Res 1997, 38:561–572.CrossRefGoogle Scholar
  30. 30.
    Zabel M, Portnoy S, Franz MR: Effect of sustained load on dispersion of ventricular repolarisation of ventricular repolarisation and conduction time in the isolated intact rabbit heart. J Cardiovasc Electrophysiol 1996, 7:9–16.PubMedCrossRefGoogle Scholar
  31. 31.
    Brilla CG, Pick R, Tan LB, et al.: Remodeling of the rat right and left ventricle in experimental hypertension. Circ Res 1990, 76:1355–1360.Google Scholar
  32. 32.
    Weber KT, Brilla CG, Campbell SE, et al.: Myocardial fibrosis: role of angiotensin II and aldosterone. Basic Res Cardiol 1993, 88(Suppl I):107–124.PubMedGoogle Scholar
  33. 33.
    Brilla CG: Aldosterone and myocardial fibrosis in heart failure. Herz 2000, 25:299–306.PubMedCrossRefGoogle Scholar
  34. 34.
    Pitt B, Zannad F, Reme WJ, et al.: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999, 341:709–717.PubMedCrossRefGoogle Scholar
  35. 35.
    Furchgott RF: Role of endothelium in responses of vascular smooth muscle. Circ Res 1983, 53:557–573.Google Scholar
  36. 36.
    Panza JA, Quyyumi A, Brush JE, Epstein SE: Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med 1990, 323:22–27.PubMedCrossRefGoogle Scholar
  37. 37.
    Perticone F, Maio R, Ceravolo R, et al.: Relationship between left ventricular mass and endothelium-dependent vasodilatation in never-treated hypertensive patients. Circulation 1999, 99:1991–1996.PubMedGoogle Scholar
  38. 38.
    Hamasaki S, Al Suwaidi J, Higano ST, et al.: Attenuated coronary flow reserve in patients with hypertension and left ventricular hypertrophy. J Am Coll Cardiol 2000, 35:1645–1660.CrossRefGoogle Scholar
  39. 39.
    Left ventricular hypertrophy patterns and prognosis. Experience post infarction in the Coronary Drug Project. Circulation 1974, 49:862–869.Google Scholar
  40. 40.
    Yotsukara M, Suzuki J, Yamaguchi T, et al.: Prognosis following acute myocardial infarction in patients with ECG evidence of left ventricular hypertrophy prior to infarction. J Electrophysiol 1998, 31:91–99.Google Scholar
  41. 41.
    Boden WE, Kleiger RE, Schechtman KB, et al.: Clinical significance and prognostic influence of left ventricular hypertrophy in non-Q wave acute myocardial infarction. Am J Cardiol 1988, 62:1000–1004.PubMedCrossRefGoogle Scholar
  42. 42.
    Behar S, Reicher-Reiss H, Abinader E, et al., and the SPRINT study group: Long term prognosis after acute myocardial infarction in patients with left ventricular hypertrophy on the electrocardiogram. Am J Cardiol 1992, 69:985–990.PubMedCrossRefGoogle Scholar
  43. 43.
    Burke AP, Farb A, Liang Y, et al.: Effect of hypertension and cardiac hypertrophy on coronary artery morphology in sudden cardiac death. Circulation 1996, 94:3138–3145.PubMedGoogle Scholar
  44. 44.
    Vogt M, Motz WH, Strauer BE: Pathophysiology and clinical aspects of hypertensive hypertrophy. Eur Heart J 1993, 145(Suppl D):2–7.Google Scholar
  45. 45.
    Kozakova M, Palombo P, Pratali L, et al.: Mechanism of coronary flow reserve impairment in human hypertension. An integrated approach by transthoracic and transoesophageal echocardiogram. Hypertension 1997, 29:551–559.PubMedGoogle Scholar
  46. 46.
    Hamouda MS, Kassem HK, Salama M, et al.: Evaluation of coronary flow reserve in hypertensive patients by dipyridamole transoesophageal doppler echocardiogram. Am J Cardiol 2000, 86:305–308.PubMedCrossRefGoogle Scholar
  47. 47.
    Simpson RJ, Casico WE, Crow RS, et al.: association of ventricular premature complexes with electrocardiographic-estimated left ventricular mass in a population of African-American and white men and women (The Atherosclerosis Risk in Communities Study). Am J Cardiol 2001, 87:49–53.PubMedCrossRefGoogle Scholar
  48. 48.
    McLenachan JM, Henderson E, Morris KI, Dargie HJ: Ventricular arrhythmias in patients with hypertensive left ventricular hypertrophy. N Engl J Med 1987, 13:787–792.CrossRefGoogle Scholar
  49. 49.
    Mantari M, Oikarinnen L, Manninen V, Viitasalo M: QT dispersion as a risk factor for sudden cardiac death and fatal myocardial infarction in a coronary risk population. Heart 1997, 78:268–272.Google Scholar
  50. 50.
    Kulan K, Ural D, Komsuoglu B, et al.: Significance of QTc prolongation on ventricular arrhythmias in patients with left ventricular hypertrophy secondary to essential hypertension. Int J Cardiol 1998, 64:179–184.PubMedCrossRefGoogle Scholar
  51. 51.
    Saadeh AM, Jones JV: Predictors of sudden cardiac death in never previously treated patients with essential hypertension: long-term follow-up. J Hum Hypertens 2001, 15:677–680.PubMedCrossRefGoogle Scholar
  52. 52.
    Hannersdorf MG, Niebch V, Perrings C, Strauer BE: T wave alterans and ventricular arrhythmias in arterial hypertension. Hypertension 2001, 37:199–203.Google Scholar
  53. 53.
    Galinier M, Balanescu S, Fourcade J, et al.: Prognostic value of ventricular arrhythmias in systemic hypertension. J Hypertens 1997, 15:1779–1783.PubMedCrossRefGoogle Scholar
  54. 54.
    Greenberg MD, Papademetriou V, Nangan P, Kokkinos P: Nonsustained ventricular tachycardia of as a predictor events in black men with hypertensive LVH. J Clin Hypertens (Greenwich) 2000, 2:14–19.Google Scholar
  55. 55.
    Pringle SD, Dunn FG, Macfarlane PW, et al.: Significance of ventricular arrhythmias in systemic hypertension with left ventricular hypertrophy. Am J Cardiol 1992, 69:913–917.PubMedCrossRefGoogle Scholar
  56. 56.
    Frimm CD, Trezza B, Gruppi C, et al.: Left ventricular hypertrophy predicts outcome of hypertension regardless of type of ventricular arrhythmia present. J Hum Hypertens 1999, 13:617–623.PubMedCrossRefGoogle Scholar
  57. 57.
    Novo S, Barbagallo M, Abrignani MG, et al.: Increased prevalence of cardiac arrhythmias and transient episodes of myocardial ischaemia in hypertensives with left ventricular hypertrophy but without clinical history of coronary heart disease. Am J Hypertens 1997, 10:843–851.PubMedCrossRefGoogle Scholar
  58. 58.
    Siscovick DS, Raghunnathan TE, Bruce M, et al.: Diuretic therapy for hypertension and the risk of primary cardiac arrest. N Engl J Med 1994, 330:1852–1857.PubMedCrossRefGoogle Scholar
  59. 59.
    Lip GYH, Beevers DG: Abnormalities of rheology and coagulation in hypertension. J Hum Hypertens 1994, 8:693–702.PubMedGoogle Scholar
  60. 60.
    Virchow R: Phlogose und Thrombose im Geraßsystem. In Gesammelte Abhandlungen zur Wissenchaftlichen Medizin. Edited by Virchow R. Frankfurt: Von Meidinger Sohn; 1856:458–636.Google Scholar
  61. 61.
    Lip GYH: Hypertension and the prothrombotic state. J Hum Hypertens 2000, 14:687–690. A good overview of the prothrombotic state in hypertension.PubMedCrossRefGoogle Scholar
  62. 62.
    Lee AJ: The role of rheological and haemostatic factors in hypertension. J Hum Hypertens 1997, 11:767–776.PubMedCrossRefGoogle Scholar
  63. 63.
    Lip GYH, Blann A: Von Willebrand factor: a marker of endothelial dysfunction in vascular disorder? Cardiovasc Res 1997, 34:255–265.PubMedCrossRefGoogle Scholar
  64. 64.
    Blann AD, Naqvi T, Waite M, McCollum CN: Von Willebrand factor and endothelial damage in essential hypertension. J Hum Hypertens 1993, 7:107–111.PubMedGoogle Scholar
  65. 65.
    Fowkes FG, Lowe GD, Rumley A, et al.: The relationship between blood viscosity and blood pressure in a random sample of the population aged 55 years to 74 years. Eur Heart J 1993, 14:597–601.PubMedGoogle Scholar
  66. 66.
    Smith WC, Lowe GD, Lee AJ, Turnstall-Pedoe H: Rheological determinants of blood pressure in a Scottish adult population. J Hypertens 1992, 10:467–472.PubMedCrossRefGoogle Scholar
  67. 67.
    Stone M, Thorpe J: Plasma fibrinogen-a major coronary risk factor. J Roy Coll Gen Prac 1985, 35:565–569.Google Scholar
  68. 68.
    Lip GYH, Blann AD, Jones AF, et al.: Relation of endothelium, thrombogenesis, and hemorheology in systemic hypertension to ethnicity and left ventricular hypertrophy. Am J Cardiol 1997, 80:1566–1571.PubMedCrossRefGoogle Scholar
  69. 69.
    Sundell IB, Nilsson T, Ramby M, et al.: Fibrinolytic variables are related to age, sex, blood pressure, and body build measurements: a cross-sectional study in Norsjo, Sweden. J Clin Epidemiol 1989, 42:719–723.PubMedCrossRefGoogle Scholar
  70. 70.
    Iso H, Folsom AR, Wu KK, et al.: Haemostatic variables in Japanese and Caucasian men. Tissue plasminogen activator, antithrombin III and protein C and their relations to coronary risk factors. Am J Epidemiol 1990, 132:41–46.PubMedGoogle Scholar
  71. 71.
    Teger-Nilsson AC, Larsson PT, Hjemdahl P, Olsson G: Fibrinogen and plasminogen activator-1 inhibitor levels in hypertension and coronary heart disease. Potential effects of beta-blockade. Circulation 1991, 84 (Suppl 6):V12-V177.Google Scholar
  72. 72.
    Ding YA, Law HW, Chou TC: Comparison of cilazapril and nifedipine retard on ambulatory blood pressure, rheological and platelet function in hypertensive patients. J Hum Hypertens 1994, 8:137–143.PubMedGoogle Scholar
  73. 73.
    Zannad F, Bray-Desboser L, el Ghawi R, etal.: Effects of lisinopril and hydrochlorothiazide on platelet function and blood rheology in essential hypertension: a randomly allocated double-blind study. J Hypertens 1993, 11:1221–1229.CrossRefGoogle Scholar
  74. 74.
    Blann AD, Lip GYH, Islim IF, Beevers DG: Evidence of platelet activation in hypertension. J Hum Hypertens 1997, 11:607–609.PubMedCrossRefGoogle Scholar
  75. 75.
    Cabezas M, Combellas A, Ramon Gomez J, etal.: Comparison of the sensitivity and specificity of the electrocardiographic criteria for left ventricular hypertrophy according to the methods of Romhilt-Estes, Sokolow-Lyon, Cornell and Rodrigez Padial. Rev Esp Cardiol 1997, 74:714–719.Google Scholar
  76. 76.
    Savage D, Garrison RJ, Kannel WB: The spectrum of left ventricular hypertrophy in a general population sample: the Framingham study. Circulation 1987, 75(Suppl I):I–26-I–33.Google Scholar
  77. 77.
    Devereux RB, Lutas EM, Casale PN: Standardization of M-mode echocardiographic left ventricular anatomic measurements. J Am Coll Cardiol 1984, 4:1222–1223.PubMedCrossRefGoogle Scholar
  78. 78.
    Neaton JD, Grimm RH, Pirneas RJ, et al.: Treatment of mild hypertension study. JAMA 1993, 270:713–724.PubMedCrossRefGoogle Scholar
  79. 79.
    Cruickshank J, Lewes J, Moore EV, Dodd C: Reversibility of ventricular hypertrophy by different types of antihypertensive therapy. J Hum Hypertens 1992, 6:85–90.PubMedGoogle Scholar
  80. 80.
    Dahlof B, Pennert K, Hansson L: Reversal of ventricular hypertrophy in hypertensive patients: a meta-analysis of 109 treatment studies. Am J Hypertens 1992, 5:95–110.PubMedGoogle Scholar
  81. 81.
    Gosse P, Sheridan DJ, Zannad F, et al.: Regression of left ventricular hypertrophy in hypertensive patients treated with indapamide SR 1.5 mg versus enalapril 20 mg: the LIVE study. J Hypertens 2000, 18:1465–1475.PubMedCrossRefGoogle Scholar
  82. 82.
    Schmieder RRE, Martus P, Klingbeil A: Reversal of left ventricular hypertrophy in essential hypertension: a meta-analysis of randomized double-blind trials. JAMA 1996, 275:1507–1513. A good meta-analysis showing the effect of drugs classes on LVH regression.PubMedCrossRefGoogle Scholar
  83. 83.
    Rials SJ, Wu Y, Ford N, et al.: Effect of left ventricular hypertrophy and its regression on ventricular electrophysiology and vulnerability to inducible arrhythmia in the feline heart. Circulation 1995, 91:426–430.PubMedGoogle Scholar
  84. 84.
    Rials SJ, Wu Y, Xu X, et al.: Regression of LVH with captopril restores normal ventricular action potential duration, dispersion of refractoriness, and vulnerability to inducible ventricular fibrillation. Circulation 1997, 96:1330–1336.PubMedGoogle Scholar
  85. 85.
    Novo S, Abrignari MG, Novo G, et al.: Effect of drug therapy on cardiac arrhythmias and ischaemia in hypertensives with left ventricular hypertrophy. Am J Hypertens 2001, 14(7 1):637–643.PubMedCrossRefGoogle Scholar
  86. 86.
    Gonzalez-Juanety JR, Garcia-Acuna JM, Pose A, et al.: Reduction of QT and QTc dispersion during long-term treatment of systemic hypertension with enalapril. Am J Cardiol 1988, 81:170–174.CrossRefGoogle Scholar
  87. 87.
    Gottdiener JS, Reda DJ, Massie BM, et al.: Veterans Association Cooperative Study Group on Antihypertensive Agents. Effect of single drug therapy on reduction of left ventricular mass in mild to moderate hypertension. Circulation 1997, 95:2007–2014.PubMedGoogle Scholar
  88. 88.
    Agabiti-Rosei E, Ambrosioni E, Dal Palu C, et al.: ACE inhibitor ramipril is more effective than the beta-blocker atenolol in reducing left ventricular mass in hypertension. Results of the RACE (ramipril cardioprotective evaluation) study. J Hypertens 1995, 13:1325–1334.PubMedCrossRefGoogle Scholar
  89. 89.
    Devereux RB, Palmieri V, Sharpe N, et al.: Effects of once daily ACE inhibition calcium channel blockade based antihypertensive treatment regimens on left ventricular hypertrophy and diastolic filling in hypertension. The prospective randomised enalapril study evaluating regression of LV enlargement (PRESERVE) study. Circulation 2001, 104:1248–1254.PubMedGoogle Scholar
  90. 90.
    Perlini S, Muiesan ML, Cuspidi C, et al.: Midwall mechanics are improved after regression of hypertensive left ventricular hypertrophy and normalization of chamber geometry. Circulation 2001, 103:678–683.PubMedGoogle Scholar
  91. 91.
    Zabalgoitia M, Rahman SN, Haley WE, et al.: Effect of regression of left ventricular hypertrophy from systemic hypertension on systolic function assessed by midwall shortening (HOT echocardiographic study). Am J Cardiol 2001, 88:521–525.PubMedCrossRefGoogle Scholar
  92. 92.
    Devereux RB, Dahlof B: Criteria for an informative trial of left ventricular hypertrophy regression. J Hum Hypertens 1994, 8:735–739. This article discusses criteria used to judge trials of LVH regression.PubMedGoogle Scholar
  93. 93.
    Mathew J, Sleight P, Lonn E, et al.: Reduction of cardiovascular risk by regression of electrocardiographic markers of left ventricular hypertrophy by angiotensin converting enzyme inhibitor ramipril. Circulation 2001, 104:1615–1621. The first study to convincingly show that regression of LVH resulted in improved prognosis.PubMedGoogle Scholar
  94. 94.
    Dahlöf B, Devereux RB, Kjeldsen SE, et al.: Cardiovascular morbidity and mortality in the Losartan Intervention For End-point reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet 2002, 359:995–1003.PubMedCrossRefGoogle Scholar
  95. 95.
    Lindholm LH, Ibsen H, Dahlöf B, et al.: Cardiovascular morbidity and mortality in the Losartan Intervention For End-point reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet 2002, 359:1004–1010.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2002

Authors and Affiliations

  • Lwin Lwin Tin
    • 1
  • D. Gareth Beevers
    • 1
  • Gregory Y. H. Lip
    • 1
  1. 1.Haemostasis, Thrombosis and Vascular Biology Unit, University Department of MedicineCity HospitalBirminghamUK

Personalised recommendations