Advertisement

Drugs

, Volume 66, Issue 2, pp 133–144 | Cite as

Impact of Increased Heart Rate on Clinical Outcomes in Hypertension

Implications for Antihypertensive Drug Therapy
  • Paolo Palatini
  • Athanase Benetos
  • Stevo Julius
Current Opinion

Abstract

Thirty-eight studies have been published to date on the association between elevated heart rate and mortality. After adjustment for other risk factors, only two studies for all-cause mortality and four studies for cardiovascular mortality reported an absence of association between heart rate and mortality in male populations. This relationship has been found to be generally weaker among females. Most of these studies investigated samples of general populations. The four studies performed in hypertensive men found a positive association between heart rate and all-cause mortality (hazard ratios ranging from 1.9 to 2.0) or cardiovascular mortality (hazard ratios ranging from 1.3 to 1.7). In spite of this evidence, elevated heart rate remains a neglected cardiovascular risk factor in both genders.

The pathogenetic mechanisms connecting high heart rate, hypertension, atherosclerosis and cardiovascular events have also been explicated in many studies. Elevated heart rate is due to an increased sympathetic and decreased parasympathetic tone. This altered balance of the autonomic nervous system tone could explain the increase in events with the increased heart rate. However, it has also been proved that blood flow changes associated with high heart rate favour both the formation of the atherosclerotic lesion and the occurrence of the cardiovascular event.

Reduction of heart rate in hypertensive patients with increased heart rate could be an additional goal of antihypertensive therapy. Several trials retrospectively showed the beneficial effect of cardiac-slowing drugs, such as β-adrenoceptor antagonists (β-blockers) and non-dihydropyridine calcium channel antagonists, on mortality, notably in patients with coronary heart disease, but no published data are available in patients with hypertension free of coronary heart disease. Other antihypertensive drugs that have been shown to reduce the heart rate are centrally acting drugs and angiotensin II receptor antagonists, but their bradycardic effect is rather weak. The f-channel antagonist ivabradine is a selective heart rate-lowering agent with no effect on blood pressure.

Although it has not been proven in existing trials, it would seem reasonable to recommend antihypertensive agents that decrease the heart rate in hypertensive patients with a heart rate higher than 80–85 beats per minute. Since the fast heart rate per se causes cardiovascular damage, all drugs that lower the heart rate have the potential of further reducing cardiovascular events in patients with elevated heart rate. Unfortunately, lowering of the heart rate is not a clinically recognised goal. Prospective trials investigating whether treatment of high heart rate can prevent cardiovascular events, notably in hypertensive patients, are warranted.

Keywords

Heart Rate Hypertensive Patient Cardiovascular Mortality Increase Heart Rate Rest Heart Rate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This work was supported by the University of Padova, Padova, Italy. The authors have no conflicts of interest that are directly relevant to the contents of this review.

References

  1. 1.
    Levy RL, White PD, Strod WD, et al. Transient tachycardia: prognostic significance alone and in association with transient hypertension. JAMA 1945; 129: 585–8CrossRefGoogle Scholar
  2. 2.
    Levy RL, Hillman CC, Stroud WD, et al. Transient hypertension: its significance in terms of later development of sustained hypertension and cardiovascular-renal diseases. JAMA 1944; 126: 829–33CrossRefGoogle Scholar
  3. 3.
    Dyer A, Persky V, Stamler J, et al. Heart rate as a prognostic factor for coronary heart disease and mortality findings in three Chicago Epidemiological Studies. Am J Epidemiol 1980; 112: 736–49PubMedGoogle Scholar
  4. 4.
    Kannel WB, Wilson P, Blair SN. Epidemiological assessment of the role of physical activity and fitness in development of cardiovascular disease. Am Heart J 1985; 109: 876–85PubMedCrossRefGoogle Scholar
  5. 5.
    Gillmann MW, Kannel WB, Belanger A, et al. Influence of heart rate on mortality among persons with hypertension: the Framingham study. Am Heart J 1993; 125: 1148–54CrossRefGoogle Scholar
  6. 6.
    Palatini P, Julius S. Heart rate and the cardiovascular risk. J Hypertens 1997; 15: 3–17PubMedCrossRefGoogle Scholar
  7. 7.
    Jouven X, Desnos M, Guerot C, et al. Predicting sudden death in the population: the Paris Prospective Study 1. Circulation 1999; 99: 1978–83PubMedCrossRefGoogle Scholar
  8. 8.
    Palatini P, Casiglia E, Julius S, et al. High heart rate: a risk factor for cardiovascular death in elderly men. Arch Intern Med 1999; 159: 585–92PubMedCrossRefGoogle Scholar
  9. 9.
    Greenland P, Daviglus ML, Dyer AR, et al. Resting heart rate is a risk factor for cardiovascular and noncardiovascular mortality. Am J Epidemiol 1999; 149: 853–62PubMedCrossRefGoogle Scholar
  10. 10.
    Benetos A, Rudnichi A, Thomas F, et al. Influence of heart rate on mortality in a French population: role of age, gender and blood pressure. Hypertension 1999; 33: 44–52PubMedCrossRefGoogle Scholar
  11. 11.
    Kristal-Boneh E, Silber H, Harari G, et al. The association of resting heart rate with cardiovascular, cancer and all-cause mortality: eight year follow-up of 3527 male Israeli employees (the CORDIS Study). Eur Heart J 2000; 21: 116–24PubMedCrossRefGoogle Scholar
  12. 12.
    Thomas F, Bean K, Provost JC, et al. Combined effects of heart rate and pulse pressure on cardiovascular mortality according to age. J Hypertens 2001; 19: 863–9PubMedCrossRefGoogle Scholar
  13. 13.
    Palatini P. Heart rate as a cardiovascular risk factor: do women differ from men? Ann Med 2001; 33: 213–21PubMedCrossRefGoogle Scholar
  14. 14.
    Benetos A, Thomas F, Bean K, et al. Resting heart rate in older people: a predictor of survival to age 85. J Am Geriatr Soc 2003; 51: 284–5PubMedCrossRefGoogle Scholar
  15. 15.
    Goldberg RJ, Larson M, Levy D. Factors associated with survival to 75 years of age in middle-aged men and women: the Framingham Study. Arch Intern Med 1996; 156: 505–9PubMedCrossRefGoogle Scholar
  16. 16.
    Palatini P, Thijs L, Staessen JA, et al. Predictive value of clinic and ambulatory heart rate for mortality in elderly subjects with systolic hypertension. Arch Intern Med 2002; 162: 2313–21PubMedCrossRefGoogle Scholar
  17. 17.
    Gillum RF, Makuc DM, Feldman JJ. Pulse rate, coronary heart disease, and death: the NHANES I Epidemiologic Follow-Up Study. Am Heart J 1991; 121: 172–7PubMedCrossRefGoogle Scholar
  18. 18.
    Kannel WB, Kannel C, Paffenbarger RS, et al. Heart rate and cardiovascular mortality: the Framingham Study. Am Heart J 1987; 113: 1489–94PubMedCrossRefGoogle Scholar
  19. 19.
    Filipovsky J, Ducimetiere P, Safar ME. Prognostic significance of exercise blood pressure and heart rate in middle-aged men. Hypertension 1992; 20: 333–9PubMedCrossRefGoogle Scholar
  20. 20.
    Sandvik L, Erikssen J, Ellestad M, et al. Heart rate increase and maximal heart rate during exercise as predictors of cardiovascular mortality: a 16-year follow-up study of 1960 healthy men. Coron Artery Dis 1995; 6: 667–79PubMedCrossRefGoogle Scholar
  21. 21.
    Mensink GB, Hoffmeister H. The relationship between resting heart rate and all-cause, cardiovascular and cancer mortality. Eur Heart J 1997; 18: 1404–10PubMedCrossRefGoogle Scholar
  22. 22.
    Reunanen A, Karjalainen J, Ristola P, et al. Heart rate and mortality. J Intern Med 2000; 247: 231–9PubMedCrossRefGoogle Scholar
  23. 23.
    Fujiura Y, Adachi H, Tsuruta M, et al. Heart rate and mortality in a Japanese general population: an 18-year follow-up study. J Clin Epidemiol 2001; 54: 495–500PubMedCrossRefGoogle Scholar
  24. 24.
    Jouven X, Zureik M, Desnos M, et al. Resting heart rate as a predictive risk factor for sudden death in middle-aged men. Cardiovasc Res 2001; 50: 373–8PubMedCrossRefGoogle Scholar
  25. 25.
    Menotti A, Mulder I, Nissinen A, et al. Cardiovascular risk factors and 10-year all-cause mortality in elderly European male populations: the FINE study. Finland, Italy, Netherlands, Elderly. Eur Heart J 2001; 22: 573–9Google Scholar
  26. 26.
    Seccareccia F, Pannozzo F, Dima F, et al. Heart rate as a predictor of mortality: the MATISS project. Am J Public Health 2001; 91: 1258–63PubMedCrossRefGoogle Scholar
  27. 27.
    Nilsson PM, Nilsson JA, Hedblad B, et al. Sleep disturbance in association with elevated pulse rate for prediction of mortality: consequences of mental strain? J Intern Med 2001; 250: 521–9PubMedCrossRefGoogle Scholar
  28. 28.
    Chang M, Havlik RJ, Corti MC, et al. Relation of heart rate at rest and mortality in the Women’s Health and Aging Study. Am J Cardiol 2003; 92: 1294–9PubMedCrossRefGoogle Scholar
  29. 29.
    Perk G, Stessman J, Ginsberg G, et al. Sex differences in the effect of heart rate on mortality in the elderly. J Am Geriatr Soc 2003; 51: 1260–4PubMedCrossRefGoogle Scholar
  30. 30.
    Hozawa A, Ohkubo T, Kikuya M, et al. Prognostic value of home heart rate for cardiovascular mortality in the general population: the Ohasama study. Am J Hypertens 2004; 17: 1005–10PubMedGoogle Scholar
  31. 31.
    Okamura T, Hayakawa T, Kadowaki T, et al. Resting heart rate and cause-specific death in a 16.5-year cohort study of the Japanese general population. Am Heart J 2004; 147: 1024–32PubMedCrossRefGoogle Scholar
  32. 32.
    Hjalmarson A, Gilpin EA, Kjekshus J, et al. Influence of heart rate on mortality after acute myocardial infarction. Am J Cardiol 1990; 65: 547–53PubMedCrossRefGoogle Scholar
  33. 33.
    Disegni E, Goldbourt U, Reicher-Reiss H, et al. The predictive value of admission heart rate on mortality in patients with acute myocardial infarction: SPRINT Study Group. Secondary Prevention Reinfarction Israeli Nifedipine Trial. J Clin Epidemiol 1995; 48: 1197–205Google Scholar
  34. 34.
    Lee KL, Woodlief LH, Topol EJ, et al. Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction: results from an international trial of 41,021 patients. GUSTO-I Investigators. Circulation 1995; 91: 1659–68Google Scholar
  35. 35.
    Copie X, Hnatkova K, Staunton A, et al. Predictive power of increased heart rate versus depressed left ventricular ejection fraction and heart rate variability for risk stratification after myocardial infarction: results of a two-year follow-up study. J Am Coll Cardiol 1996; 27: 270–6PubMedCrossRefGoogle Scholar
  36. 36.
    Marchioli R, Avanzini F, Barzi F, et al. Assessment of absolute risk of death after myocardial infarction by use of multiple-risk-factor assessment equations: GISSI-Prevenzione mortality risk chart. Eur Heart J 2001; 22: 2085–103PubMedCrossRefGoogle Scholar
  37. 37.
    Berton GS, Cordiano R, Palmieri R, et al. Heart rate during myocardial infarction: relationship with one-year global mortality in men and women. Can J Cardiol 2002; 18: 495–502PubMedGoogle Scholar
  38. 38.
    Abildstrom SZ, Jensen BT, Agner E, et al. Heart rate versus heart rate variability in risk prediction after myocardial infarction. J Cardiovasc Electrophysiol 2003; 14: 168–73PubMedCrossRefGoogle Scholar
  39. 39.
    Kovar D, Cannon CP, Bentley JH, et al. Does initial and delayed heart rate predict mortality in patients with acute coronary syndromes? Clin Cardiol 2004; 27: 80–6PubMedCrossRefGoogle Scholar
  40. 40.
    Sega R, Facchetti R, Bombelli M, et al. Prognostic value of ambulatory and home blood pressures compared with office blood pressure in the general population: follow-up results from the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study. Circulation 2005; 111: 1777–83PubMedCrossRefGoogle Scholar
  41. 41.
    Jouven X, Empana JP, Schwartz PJ, et al. Heart-rate profile during exercise as a predictor of sudden death. N Engl J Med 2005; 352: 1951–8PubMedCrossRefGoogle Scholar
  42. 42.
    Thomas F, Rudnichi A, Bacri AM, et al. Cardiovascular mortality in hypertensive men according to presence of associated risk factors. Hypertension 2001; 37: 1256–61PubMedCrossRefGoogle Scholar
  43. 43.
    Goldring W, Chassis H. Antihypertensive therapy: an appraisal. In: Ingelfienger J, Relman AS, Finland A, editors. Controversies in internal medicine. Philadelphia (PA): WB Saunders Publishers, 1966: 83Google Scholar
  44. 44.
    Erikssen J, Rodahl K. Resting heart rate in apparently healthy middle-aged men. Eur J Appl Physiol 1979; 42: 61–9CrossRefGoogle Scholar
  45. 45.
    Berenson GS, Voors AW, Webber LS, et al. Racial differences of parameters associated with blood pressure levels in children: the Bogalusa Heart Study. Metabolism 1979; 28: 1218–28PubMedCrossRefGoogle Scholar
  46. 46.
    Kim JR, Kiefe CL, Liu K, et al. Heart rate and subsequent blood pressure in young adults: the CARDIA Study. Hypertension 1999; 33: 640–6PubMedCrossRefGoogle Scholar
  47. 47.
    Selby JV, Friedman GD, Quensenberry CP. Precursors of essential hypertension: pulmonary function, heart rate, uric acid, serum cholesterol, and other serum chemistries. Am J Epidemiol 1990; 131: 1017–27PubMedGoogle Scholar
  48. 48.
    Paffenbarger RS, Thorne MC, Wing AL. Chronic disease in former college students: VIII. Characteristics in youth predisposing to hypertension in later years. Am J Epidemiol 1968; 88: 25–32Google Scholar
  49. 49.
    Mo R, Nordrehaug JE, Omvik P, et al. The Bergen Blood Pressure Study: prehypertensive changes in cardiac structure and function in offspring of hypertensive families. Blood Press 1995; 4: 16–22PubMedCrossRefGoogle Scholar
  50. 50.
    Benetos A, Adamopoulos C, Bureau J-M, et al. Determinants of accelerated progression of arterial stiffness in normotensive and treated hypertensive subjects over a 6-year period. Circulation 2002; 105: 1202–7PubMedCrossRefGoogle Scholar
  51. 51.
    Julius S, Pascual AV, London R. Role of parasympathetic inhibition in the hyperkinetic type of borderline hypertension. Circulation 1971; 44: 413–8PubMedCrossRefGoogle Scholar
  52. 52.
    Palatini P, Julius S. Association of tachycardia with morbidity and mortality: pathophysiological considerations. J Hum Hypertens 1997; 11 Suppl. 1: 19–27Google Scholar
  53. 53.
    Palatini P, Casiglia E, Pauletto P, et al. Relationship of tachycardia with high blood pressure and metabolic abnormalities: a study with mixture analysis in three populations. Hypertension 1997; 30: 1267–73PubMedCrossRefGoogle Scholar
  54. 54.
    Bonaa KH, Arnesen E. Association between heart rate and atherogenic blood lipid fractions in a population: the Tromso Study. Circulation 1992; 86: 394–405PubMedCrossRefGoogle Scholar
  55. 55.
    Julius S, Valentini M, Palatini P. Overweight and hypertension: a two-way street? Hypertension 2000; 35: 807–13PubMedCrossRefGoogle Scholar
  56. 56.
    Valentini M, Julius S, Palatini P, et al. Attenuation of hemodynamic, metabolic and energy expenditure responses to isoproterenol in patients with hypertension. J Hypertens 2004; 22: 1999–2006PubMedCrossRefGoogle Scholar
  57. 57.
    Bassiouny HS, Zarins CK, Kadowaki MH, et al. Hemodynamic stress and experimental aortoiliac atherosclerosis. J Vasc Surg 1994; 19: 426–34PubMedCrossRefGoogle Scholar
  58. 58.
    Beere PA, Glagov S, Zarins CK. Retarding effect of lowered heart rate on coronary atherosclerosis. Science 1984; 226: 180–2PubMedCrossRefGoogle Scholar
  59. 59.
    Kaplan JR, Manuck SB, Adams MR, et al. Inhibition of coronary atherosclerosis by propranolol in behaviorally predisposed monkeys fed an atherogenic diet. Circulation 1987; 76: 1364–72PubMedCrossRefGoogle Scholar
  60. 60.
    Mangoni AA, Mircoli L, Giannattasio C, et al. Heart rate-dependence of arterial distensibility in vivo. J Hypertens 1996; 14: 897–901PubMedCrossRefGoogle Scholar
  61. 61.
    Albaladejo P, Carusi A, Apartian A, et al. Effect of chronic heart rate reduction with ivabradine on carotid and aortic structure and function in normotensive and hypertensive rats. J Vasc Res 2003; 40: 320–8PubMedCrossRefGoogle Scholar
  62. 62.
    Heidland UE, Strauer BE. Left ventricular muscle mass and elevated heart rate are associated with coronary plaque disruption. Circulation 2001; 104: 1477–82PubMedCrossRefGoogle Scholar
  63. 63.
    Julius S. Altered cardiac responsiveness and regulation in the normal cardiac output type of borderline hypertension. Circ Res 1975; 36–37 Suppl. I: 1199–207Google Scholar
  64. 64.
    Vogel CU, Wolpert C, Wehling M. How to measure heart rate? Eur J Clin Pharmacol 2004; 60: 461–6PubMedCrossRefGoogle Scholar
  65. 65.
    Paffenbarger RS, Hyde RT, Wing AL, et al. Physical activity, all-cause mortality, and longevity of college alumni. N Engl J Med 1986; 314: 605–13PubMedCrossRefGoogle Scholar
  66. 66.
    Watts K, Jones TW, Davis EA, et al. Exercise training in obese children and adolescents: current concepts. Sports Med 2005; 35: 375–92PubMedCrossRefGoogle Scholar
  67. 67.
    Teo KK, Yusuf S, Furberg CD. Effects of prophylactic antiarrhythmic drug therapy in acute myocardial infarction: an overview of results from randomized controlled trials. JAMA 1993; 270: 1589–95PubMedCrossRefGoogle Scholar
  68. 68.
    The Multicenter Diltiazem Postinfarction Trial Research Group. The effect of diltiazem on mortality and reinfarction after myocardial infarction. N Engl J Med 1988; 319: 385–92CrossRefGoogle Scholar
  69. 69.
    Palatini P. Treatment of tachycardia in hypertension: where do we stand now? Curr Hypertens Rev 2005; 1: 129–40CrossRefGoogle Scholar
  70. 70.
    Kjekshus JK. Importance of heart rate in determining beta-blocker efficacy in acute and long-term acute myocardial infarction intervention trials. Am J Cardiol 1986; 57: 43–49FCrossRefGoogle Scholar
  71. 71.
    Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure: U.S. Carvedilol Heart Failure Study Group. N Engl J Med 1996; 334: 1349–55Google Scholar
  72. 72.
    MRC Working Party. Medical Research Council trial of treatment of hypertension in older adults: principal results. BMJ 1992; 304: 405–12CrossRefGoogle Scholar
  73. 73.
    Collins R, Peto R, MacMahon S, et al. Blood pressure, stroke, and coronary heart disease. Part 2: short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 1990; 335: 827–38Google Scholar
  74. 74.
    Dahlöf B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention for Endpoint Reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet 2002; 359: 996–1003Google Scholar
  75. 75.
    Dahlof B, Sever PS, Poulter NR, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005; 366: 869–71CrossRefGoogle Scholar
  76. 76.
    Pollare T, Lithell H, Morlin C, et al. Metabolic effects of diltiazem and atenolol: results from a randomized, double-blind study with parallel groups. J Hypertens 1989; 7: 551–9PubMedCrossRefGoogle Scholar
  77. 77.
    ALLHAT Officers and Coordinators, ALLHAT Collaborative 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: 2981–97CrossRefGoogle Scholar
  78. 78.
    Jamerson KA, Julius S, Gudbrandsson T, et al. Reflex sympathetic activation induces acute insulin resistance in the human forearm. Hypertension 1993; 21: 618–23PubMedCrossRefGoogle Scholar
  79. 79.
    Kailasam MT, Partner RJ, Cervenka JH, et al. Divergent effects of dihydropyridine and phenylalkylamine calcium channel antagonist classes on autonomic function in human hypertension. Hypertension 1995; 26: 143–9PubMedCrossRefGoogle Scholar
  80. 80.
    The Danish Study Group on Verapamil in Myocardial Infarction. Effect of verapamil on mortality and major events after acute myocardial infarction: the Danish Verapamil Infarction Trial II (DAVIT-II). Am J Cardiol 1990; 66: 779–85CrossRefGoogle Scholar
  81. 81.
    Messerli FH, Hansen JF, Gibson RS, et al. Heart rate-lowering calcium antagonists in hypertensive post-myocardial infarction patients. J Hypertens 2001; 19: 977–82PubMedCrossRefGoogle Scholar
  82. 82.
    Wellington K, Scott LJ. Azelnidipine. Drugs 2003; 63: 2613–21PubMedCrossRefGoogle Scholar
  83. 83.
    Kuramoto K, Ichikawa S, Hirai A, et al. Azelnidipine and amlodipine: a comparison of their pharmacokinetics and effects on ambulatory blood pressure. Hypertens Res 2003; 26: 201–8PubMedCrossRefGoogle Scholar
  84. 84.
    Van Zwieten PA. Centrally acting antihypertensives: a renaissance of interest. Mechanisms and haemodynamics. J Hypertens 1997; 15 Suppl. 1: S3–8CrossRefGoogle Scholar
  85. 85.
    Leu HB, Charng MJ, Ding PY. A double blind randomized trial to compare the effects of eprosartan and enalapril on blood pressure, platelets, and endothelium function in patients with essential hypertension. Jpn Heart J 2004; 45: 623–35PubMedCrossRefGoogle Scholar
  86. 86.
    Kaul CL, Ramarao P. Renin release and the sympathetic nervous system. Drugs Today (Barc) 2000; 36: 699–713Google Scholar
  87. 87.
    Palatini P, Mugellini A, Spagnuolo V, et al. Comparison of the effects on 24-h ambulatory blood pressure of valsartan and amlodipine, alone or in combination with a low-dose diuretic, in elderly patients with isolated systolic hypertension (Val-syst Study). Blood Press Monit 2004; 9: 91–7PubMedCrossRefGoogle Scholar
  88. 88.
    Di Francesco D. The contribution of the ‘pacemaker’ current (If) to generation of spontaneous activity in rabbit sino-atrial node myocytes. J Physiol 1991; 434: 23–40Google Scholar
  89. 89.
    Di Francesco D, Camm JA. Heart rate lowering by specific and selective I(f) current inhibition with ivabradine: a new therapeutic perspective in cardiovascular disease. Drugs 2004; 64: 1757–65CrossRefGoogle Scholar
  90. 90.
    Farinaro E, Stranges S, Guglielmucci G, et al. Heart rate as a risk factor in hypertensive individuals: the Italian TensioPulse Study. Nutr Metab Cardiovasc Dis 1999; 9: 196–202PubMedGoogle Scholar
  91. 91.
    European Society of Hypertension-European Society of Cardiology Guidelines Committee. 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21(6): 1011–53CrossRefGoogle Scholar
  92. 92.
    Palatini P. Need for a revision of the normal limits of resting heart rate. Hypertension 1999; 33: 622–5PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • Paolo Palatini
    • 1
  • Athanase Benetos
    • 2
  • Stevo Julius
    • 3
  1. 1.Department of Clinical and Experimental MedicineUniversity of PadovaPadovaItaly
  2. 2.Unité d’Expertise et de Prévention GériatriqueCHU NancyVandoeuvre lès NancyFrance
  3. 3.Division of HypertensionUniversity of MichiganAnn ArborUSA

Personalised recommendations