Modifications of Blood Pressure Profiles in the Very Old: Role of Frailty and Comorbidities

  • Athanase BenetosEmail author
  • Sylvie Gautier
  • Michel E. Safar


The 2013 ESC-ESH Guidelines for the management of arterial hypertension stated that in elderly (>80 years) individuals, lowering SBP to < 150mmHg is strongly evidence-based. These guidelines are mainly based on the results of the Hypertension in the Very Elderly (HYVET) study which showed the beneficial effect of decreasing SBP with antihypertensive treatment in patients older than 80 years. This trial was conducted in a highly selected population of robust elderly patients with very low comorbidities. Thus, despite the interest of these results, we believe that the question of the benefits of antihypertensive treatment in the very old is not unequivocally settled and may depend on the magnitude of co-morbidities, frailty and functional decline.

The PARTAGE (Predictive values of blood pressure and arterial stiffness in institutionalized very aged population) multicenter study performed in very old, frail subjects living in nursing homes reported a 30% increase in all-cause mortality in patients ranked in the lowest tertile of SBP (<130mmHg) compared to the two upper tertiles. These results remained identical after adjusting for several confounders such as age, gender, history of previous CV disease, index of co-morbidity, cognitive function and autonomy status. These paradoxical results can be explained by the fact that in these very old frail subjects, a low SBP may not simply be a sign of so-called good arterial health, but often of malnutrition and of co-morbidities such as heart failure, neurological disorders etc., as well as other concomitant conditions associated with poor prognosis. Irrespective of the underlying explanation, the present results indicate that the BP levels in very old “frail” individuals are evidently not reliable. These findings raise the question as to relevance of BP levels as an indicator of the cardiovascular risk in these subjects. This is of major interest since iatrogenic-induced problems are also a major issue in geriatric subjects. In fact, at the present time, no study has provided evidence that higher morbidity-mortality rates in those with very low BP is due to low BP in itself or is just a sign of general bad health.

Interventional clinical trials will provide critical information to guide physicians in order to fixe specific goals for treating hypertension and decreasing the risk of cardiovascular complications in these very old and frail individuals.


Elderly population Comorbidities Geriatric medicine Cardiovascular risk Alzheimer’s disease 


  1. 1.
    Tolson D, Morley JE, Rolland Y, Vellas B. Advancing nursing home practice: the International Association of Geriatrics and Gerontology Recommendations. Geriatr Nurs. 2011;32:195–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Authors/Task Force Members, Mancia G, Fagard R, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34:2159–219.PubMedCrossRefGoogle Scholar
  3. 3.
    Alagiakrishnan K, Juby A, Hanley D, Tymchak W, Sclater A. Role of vascular factors in osteoporosis. J Gerontol. 2003;58:362–6.CrossRefGoogle Scholar
  4. 4.
    Launer L, Webster Ross G, Petrovitch H, Masaki K, Foley D, White LR, Havlik RJ. Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging. 2000;21:49–55.PubMedCrossRefGoogle Scholar
  5. 5.
    Franco OH, Peeters A, Bonneux L, De Laet C. Blood pressure in adulthood and life expectancy with cardiovascular disease in men and women: life course analysis. Hypertension. 2005;46:280–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Benetos A, Thomas F, Bean KE, Pannier B, Guize L. Role of modifiable risk factors in life expectancy in the elderly. J Hypertens. 2005;23:1803–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Lewington S, Clarke R, Qizilbash 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
  8. 8.
    Chobanian AV, Bakris GL, Black HR, et al. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute. National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206–52.Google Scholar
  9. 9.
    Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ. 2009;338:b1665. doi: 10.1136/bmj.b1665.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Turnbull F, Neal B, Ninomiya T, Blood Pressure Lowering Treatment Trialists’ Collaboration, et al. Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials. BMJ. 2008;336:1121–3.PubMedCrossRefGoogle Scholar
  11. 11.
    Blood Pressure Lowering Treatment Trialists C, Turnbull F, Neal B, et al. Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials. BMJ. 2008;336:1121–3.PubMedCrossRefGoogle Scholar
  12. 12.
    Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA. 1991;265:3255–64.Google Scholar
  13. 13.
    Dahlof B, Lindholm LH, Hansson L, et al. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Lancet. 1991;338:1281–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Medical Research Council trial of treatment of hypertension in older adults: principal results. MRC Working Party. BMJ. 1992;304:405–12.Google Scholar
  15. 15.
    Staessen JA, Fagard R, Thijs L, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet. 1997;350:757–64.PubMedCrossRefGoogle Scholar
  16. 16.
    Liu L, Wang JG, Gong L, et al. Comparison of active treatment and placebo in older Chinese patients with isolated systolic hypertension. Systolic Hypertension in China (Syst-China) Collaborative Group. J Hypertens. 1998;16:1823–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358:1887–98.PubMedCrossRefGoogle Scholar
  18. 18.
    Benetos A, Zureik M, Morcet J, et al. A decrease in diastolic blood pressure combined with an increase in systolic blood pressure is associated with a higher cardiovascular mortality in men. J Am Coll Cardiol. 2000;35:673–80.PubMedCrossRefGoogle Scholar
  19. 19.
    Franklin SS, Khan SA, Wong ND, Larson MG, Levy D. Is pulse pressure useful in predicting risk for coronary heart disease ? Circulation. 1999;100:354–60.PubMedCrossRefGoogle Scholar
  20. 20.
    Khattar RS, Swales JD, Dore C, Senior R, Lahiri A. Effects of aging on the prognostic significance of ambulatory systolic, diastolic and pulse pressure in essential hypertension. Circulation. 2001;104:783–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Blacher J, Staessen JA, Girerd X, et al. Pulse pressure not mean pressure determines cardiovascular risk in older hypertensive patients. Arch Intern Med. 2000;160:1085–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Boshuizen HC, Izaks GJ, van Buuren S, Ligthart GJ. Blood pressure and mortality in elderly people aged 85 and older: community based study. BMJ. 1998;316:1780–4.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Satish S, Zhang DD, Goodwin JS. Clinical significance of falling blood pressure among older adults. J Clin Epidemiol. 2001;54:961–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Meaume S, Benetos A, Henry OF, et al. Aortic pulse wave velocity predicts cardiovascular mortality in subjects >70 years of age. Arterioscler Thromb Vasc Biol. 2001;21:2046–50.PubMedCrossRefGoogle Scholar
  25. 25.
    Askari M, Kiely DK, Lipsitz LA. Is pulse pressure a predictor of cardiovascular complications in a frail elderly nursing home population? Aging Clin Exp Res. 2004;16:206–11.PubMedCrossRefGoogle Scholar
  26. 26.
    Oates DJ, Berlowitz DR, Glickman ME, et al. Blood pressure and survival in the oldest old. J Am Geriatr Soc. 2007;55:383–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Molander L, Lovheim H, Norman T, et al. Lower systolic blood pressure is associated with greater mortality in people aged 85 and older. J Am Geriatr Soc. 2008;56:1853–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Lagaay AM, van Asperen IA, Hijmans W. The prevalence of morbidity in the oldest old, aged 85 and over: a population-based survey in Leiden, The Netherlands. Arch Gerontol Geriatr. 1992;15:115–31.PubMedCrossRefGoogle Scholar
  29. 29.
    Rastas S, Pirttila T, Viramo P, et al. Association between blood pressure and survival over 9 years in a general population aged 85 and older. J Am Geriatr Soc. 2006;54:912–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Ogihara T. Practitioner’s trial on the efficacy of antihypertensive treatment in the elderly hypertension (the PATE-hypertension study) in Japan. Am J Hypertens. 2000;13:461–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Fagard RH, Staessen JA, Thijs L, et al. On-treatment diastolic blood pressure and prognosis in systolic hypertension. Arch Intern Med. 2007;167:1884–91.PubMedCrossRefGoogle Scholar
  32. 32.
    Somes GW, Pahor M, Shorr RI, et al. The role of diastolic blood pressure when treating isolated systolic hypertension. Arch Intern Med. 1999;159:2004–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Perry Jr HM, Davis BR, Price TR, et al. Effect of treating isolated systolic hypertension on the risk of developing various types and subtypes of stroke: the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 2000;284:465–71.PubMedCrossRefGoogle Scholar
  34. 34.
    Benetos A, Salvi P, Lacolley P. Blood pressure regulation during the aging process: the end of the ‘hypertension era’? J Hypertens. 2011;29:646–52.PubMedCrossRefGoogle Scholar
  35. 35.
    Safar ME, Levy BI, Struijker-Boudier H. Current perspectives on arterial stiffness and pulse pressure in hypertension and cardiovascular disease. Circulation. 2003;107:2864–9.PubMedCrossRefGoogle Scholar
  36. 36.
    O’Rourke MF, Frolich ED. Pulse pressure: is this a clinically useful risk factor ? Hypertension. 1999;34:372–4.PubMedCrossRefGoogle Scholar
  37. 37.
    Lakatta E. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part III: cellular and molecular clues to heart and arterial aging. Circulation. 2003;107:490–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Benetos A, Adamopoulos C, Bureau JM, et al. Determinants of accelerated progression of arterial stiffness in normotensive subjects and in treated hypertensive subjects over a 6-year period. Circulation. 2002;105:1202–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Benetos A, Buatois S, Salvi P, et al. Blood pressure and pulse wave velocity values in the institutionalized elderly aged 80 and over: baseline of the PARTAGE Study. J Hypertens. 2010;28:41–50.PubMedCrossRefGoogle Scholar
  40. 40.
    Ronnback M, Fagerudd J, Forsblom C, Pettersson-Fernholm K, Reunanen A, Groop PH, on behalf of Finnish Diabetic Nephropathy Study Group. Altered age-related blood pressure pattern in type 1 diabetes. Circulation. 2004;110:1076–82.Google Scholar
  41. 41.
    Salomaa V, Riley W, Kark JD, Nardo C, Folsom AR. Non-insulin dependent diabetes mellitus and fasting glucose and insulin concentrations are associated with arterial stiffness indexes. ARIC Study Circulation. 1995;91:1432–43.CrossRefGoogle Scholar
  42. 42.
    Schram MT, Kostense PJ, Van Dijk RA, et al. Diabetes, pulse pressure and cardiovascular mortality: the Hoorn Study. J Hypertens. 2002;20:1743–51.PubMedCrossRefGoogle Scholar
  43. 43.
    Franklin SS, Larson MG, Khan SA, et al. Does the relation of blood pressure to coronary heart disease risk change with aging? Framingham Heart Study Circulation. 2001;103:1245–9.CrossRefGoogle Scholar
  44. 44.
    European Society of Hypertension-European Society of Cardiology Guidelines Committee. 2003 European Society of Hypertension–European Society of Cardiology Guidelines Committee. Guidelines for the management of arterial hypertension. J Hypertens. 2003;21:1011–53.CrossRefGoogle Scholar
  45. 45.
    Darne B, Girerd X, Safar M, Cambien F, Guize L. Pulsatile versus steady component of blood pressure: a cross-sectional analysis and a prospective analysis on cardiovascular mortality. Hypertension. 1989;13:392–400.PubMedCrossRefGoogle Scholar
  46. 46.
    Mitchell GF, Moye LA, Braunwald E, et al. for the SAVE Investigators. Sphygmomanometric determined pulse pressure is a powerful independent predictor of recurrent events after myocardial infarction in patients with impaired left ventricular function. Circulation. 1997;96:4254–60.Google Scholar
  47. 47.
    Chae CU, Pfeffer MA, Glynn RJ, Mitchell GF, Taylor JO, Hennekens CH. Increased pulse pressure and risk of heart failure in the elderly. JAMA. 1999;281:634–9.PubMedCrossRefGoogle Scholar
  48. 48.
    Benetos A, Safar M, Rudnichi A, et al. Pulse pressure, a predictor of long-term cardiovascular mortality. Hypertension. 1997;30:1410–5.PubMedCrossRefGoogle Scholar
  49. 49.
    Kengne AP, Czernichow S, Huxley R, et al. Blood pressure variables and cardiovascular risk new findings from ADVANCE. Hypertension. 2009;54:399–404.PubMedCrossRefGoogle Scholar
  50. 50.
    Bangalore S, Messerli FH, Franklin SS, Mancia G, Champion A, Pepine CJ. Pulse pressure and risk of cardiovascular outcomes in patients with hypertension and coronary artery disease: an INternational VErapamil SR-trandolapril Study (INVEST) analysis. Eur Heart J. 2009;30:1395–401.PubMedCrossRefGoogle Scholar
  51. 51.
    Miura K, Nakagawa H, Ohashi Y, et al. Four blood pressure indexes and the risk of stroke and myocardial infarction in Japanese men and women. A meta-analysis of 16 cohort studies. Circulation. 2009;119:1892–8.PubMedCrossRefGoogle Scholar
  52. 52.
    Benetos A, Rudnichi A, Safar M, Guize L. Pulse pressure and cardiovascular mortality in normotensive and hypertensive subjects. Hypertension. 1998;32:560–4.PubMedCrossRefGoogle Scholar
  53. 53.
    de Simone G, Roman MJ, Alderman MH, Galderisi M, de Divitiis O, Devereux RB. Is high pulse pressure a marker of preclinical cardiovascular disease? Hypertension. 2005;45:575–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Gasowski J, Fagard RH, Staessen JA, et al. INDANA Project Collaborators. Pulsatile blood pressure component as predictor of mortality in hypertension: a meta-analysis of clinical trial control groups. J Hypertens. 2002;20:145–51.Google Scholar
  55. 55.
    Nichols WW, O’Rourke MF. McDonald’s blood flow in arteries. Theoretical, experimental and clinical principles. 5th ed. London: Edward Arnold; 2005.Google Scholar
  56. 56.
    Safar ME, Smulyan H. Coronary ischemic disease, arterial stiffness, and pulse pressure. Am J Hypertens. 2004;17:724–6.PubMedCrossRefGoogle Scholar
  57. 57.
    Kass DA. Ventricular arterial stiffening: integrating the pathophysiology. Hypertension. 2005;46:185–93.PubMedCrossRefGoogle Scholar
  58. 58.
    Lloyd-Jones DM, Evans JC, Levy D. Hypertension in adults across the age spectrum: current outcomes and control in the community. JAMA. 2005;294:466–72.PubMedCrossRefGoogle Scholar
  59. 59.
    Benetos A, Gautier S, Labat C, et al. Mortality and cardiovascular events are best predicted by low central/peripheral pulse pressure amplification but not by high blood pressure levels in elderly nursing home subjects: the PARTAGE (Predictive Values of Blood Pressure and Arterial Stiffness in Institutionalized Very Aged Population) study. J Am Coll Cardiol. 2012;60:1503–11.PubMedCrossRefGoogle Scholar
  60. 60.
    Skoog I, Lernfelt B, Landahl S, et al. 15-year longitudinal study of blood pressure and dementia. Lancet. 1996;347:1141–5.PubMedCrossRefGoogle Scholar
  61. 61.
    Vanhanen H, Thijs L, Birkenhager W, Bulpitt C, Tilvis R, Sarti C, Tuomilehto J, Staessen JA. Prevalence and persistency of orthostatic blood pressure fall in older patients with isolated systolic hypertension. Syst-Eur Investigators. Hum Hypertens. 1996;10:607–12.Google Scholar
  62. 62.
    Staessen JA, Thijs L, O’Brien ET, et al. Ambulatory pulse pressure as predictor of outcome in older patients with systolic hypertension. Am J Hypertens. 2002;15:835–43.PubMedCrossRefGoogle Scholar
  63. 63.
    Staessen JA, Thijs L, Fagard R, et al. Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension. JAMA. 1999;282:539–46.PubMedCrossRefGoogle Scholar
  64. 64.
    Fagard RH, Staessen JA, Thijs L, et al. Response to antihypertensive therapy in older patients with sustained and nonsustained systolic hypertension. Circulation. 2000;102:1139–44.PubMedCrossRefGoogle Scholar
  65. 65.
    Bobrie G, Chatellier G, Genes N, Clerson P, Vaur L, Vaisse B, Menard J, Mallion JM. Cardiovascular prognosis of “masked hypertension” detected by blood pressure self-measurement in elderly treated hypertensive patients. JAMA. 2004;291:1342–9.PubMedCrossRefGoogle Scholar
  66. 66.
    Björklund K, Lind L, Zethelius B, Berglund L, Lithell H. Prognostic significance of 24-h ambulatory blood pressure characteristics for cardiovascular morbidity in a population of elderly men. J Hypertens. 2004;22:1691–7.PubMedCrossRefGoogle Scholar
  67. 67.
    Asayama K, Ohkubo T, Kikuya M, Metoki H, Hoshi H, Hashimoto J, Totsune K, Satoh H, Imai Y. Prediction of stroke by self-measurement of blood pressure at home versus casual screening blood pressure measurement in relation to the Joint National Committee 7 classification: the Ohasama study. Stroke. 2004;35:2356–61.PubMedCrossRefGoogle Scholar
  68. 68.
    Mac Mahon M, Sheahan NF, Colgan MP, Walsh B, Malone J, Coakley D. Arterial closing pressure correlates with diastolic pseudohypertension in the elderly. J Gerontol A Biol Sci Med Sci. 1995;50A:56–8.CrossRefGoogle Scholar
  69. 69.
    Franklin SS, Wilkinson IB, McEniery CM. Unusual hypertensive phenotypes: what is their significance? Hypertension. 2012;59:173–8.PubMedCrossRefGoogle Scholar
  70. 70.
    Clinical practice guidelines: management of adults with essential hypertension- 2005 update – Société française d’hypertension artérielle. Haute Autorité de Santé HAS July 2005. Management of adults with essential hypertension-2005 update-guidelines. J Mal Vasc. 2006;31:16–33.Google Scholar
  71. 71.
    The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) 2007. Guidelines for the management of arterial hypertension. J Hypertens. 2007;25:1105–87.Google Scholar
  72. 72.
    Mancia G, Laurent S, Agabiti-Rosei E. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. J Hypertens. 2009;27:2121–58.PubMedCrossRefGoogle Scholar
  73. 73.
    Burt VL, Cutler JA, Higgins M, et al. Trends in the prevalence, awareness, treatment, and control of hypertension in the adult US population: data from the Health Examination Surveys, 1960 to 1991. Hypertension. 1995;26:60–9.PubMedCrossRefGoogle Scholar
  74. 74.
    Marques-Vidal P, Tuomilehto J. Hypertension awareness, treatment and control in the community: is the “rule of halves” still valid? J Hum Hypertens. 1997;11:213–20.PubMedCrossRefGoogle Scholar
  75. 75.
    Colhoun HM, Dong W, Poulter NR. Blood pressure screening, management and control in England: results from the health survey for England 1994. J Hypertens. 1998;16:747–52.PubMedCrossRefGoogle Scholar
  76. 76.
    Perret-Guillaume C, Miget P, Aubry C, Gueguen R, Steyer E, Benetos A. Contrôle de la pression artérielle par le traitement antihypertenseur chez le sujet de plus de 60 ans. Rev Med Interne. 2006;27:285–90.PubMedCrossRefGoogle Scholar
  77. 77.
    Benetos A, Thomas F, Bean K, Gautier S, Smulyan H, Guize L. Prognostic value of systolic and diastolic pressure in treated hypertensive men. Arch Intern Med. 2002;162:577–81.PubMedCrossRefGoogle Scholar
  78. 78.
    Chobanian AV. The hypertension paradox – More uncontrolled disease despite improved therapy. N Engl J Med. 2009;361:878–87.PubMedCrossRefGoogle Scholar
  79. 79.
    Kannel WB, Wilson PWF, Nam BH, D’Agostino RB, Li J. A likely explanation for the J-curve of blood pressure cardiovascular risk. Am J Cardiol. 2004;94:380–4.PubMedCrossRefGoogle Scholar
  80. 80.
    Messerli FH, Mancia G, Conti CR, et al. Dogma disputed: can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? Ann Intern Med. 2006;44:884–93.CrossRefGoogle Scholar
  81. 81.
    Messerli FH, Panjrath GS. The J-curve between blood pressure and coronary artery disease or essential hypertension: exactly how essential? J Am Coll Cardiol. 2009;54:1827–34.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  • Athanase Benetos
    • 1
    • 2
    Email author
  • Sylvie Gautier
    • 1
  • Michel E. Safar
    • 3
  1. 1.Department of GeriatricsUniversity Hospital of Nancy, Universite De LorraineVandoeuvre Les NancyFrance
  2. 2.INSERM U1116,Université de LorraineNancyFrance
  3. 3.Department of MedicineParis Descartes University, Assistance Publique des Hôpitaux de Paris – Hôtel-Dieu Hospital, Diagnosis and Therapeutics CenterParisFrance

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