Advertisement

Hypertension Management at Older Age: An Update

  • Rita Del PintoEmail author
  • Claudio Ferri
Review Article
  • 47 Downloads

Abstract

Hypertension is a risk factor for cardiovascular morbidity and mortality with increasing prevalence with age, whose treatment is associated with benefits over fatal and non-fatal cardiovascular events even later in life. However, there are persistent concerns on the short- and long-term weighted benefits of treating hypertension in the very old, particularly in those with specific clinical features. In fact, a broad range of clinical scenarios can be observed at older ages, spanning from the healthy to the frailest patient, and hypertension clinical trials have traditionally excluded the latter, thus preventing the unconditioned application to these patients of the same recommendations as in younger ages. Persistent issues regarding high blood pressure management in the very old adult are mainly related to treatment threshold and targets, which have been differently addressed by American and European guidelines. Herein, we will examine the challenges related to high blood pressure treatment in healthy and frail older and very old adults. We will discuss the evidence behind current recommendations. Finally, we will recapitulate the recommended treatment options for high blood pressure in these patients in the light of the most recent guidelines.

Keywords

Aging Hypertension Antihypertensive agents Cardiovascular diseases Cerebrovascular diseases Frailty 

Notes

Authors contribution

CF conceived the manuscript and provided critical guidance, RDP wrote the first draft, RDP and CF edited the manuscript. Both authors read and approved the final version of the manuscript.

Compliance with ethical standards

Funding

None.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. 1.
    Aronow WS, Fleg JL, Pepine CJ, Artinian NT, Bakris G, Brown AS, et al. ACCF/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus documents developed in collaboration with the American Academy of Neurology, American Geriatrics Society, American Society for Preventive Cardiology, American Society of Hypertension, American Society of Nephrology, Association of Black Cardiologists, and European Society of Hypertension. J Am Coll Cardiol. 2011;57:2037–114.Google Scholar
  2. 2.
    Franklin SS. Ageing and hypertension: the assessment of blood pressure indices in predicting coronary heart disease. J Hypertens Suppl. 1999;17:S29–36.Google Scholar
  3. 3.
    Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358:1887–98.Google Scholar
  4. 4.
    The Systolic Hypertension in the Elderly Program (SHEP) Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the SHEP. JAMA. 1991;265:3255–64.  https://doi.org/10.1001/jama.1991.03460240051027.Google Scholar
  5. 5.
    Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:1269–324.Google Scholar
  6. 6.
    Mancia G, Fagard R, Narkiewicz K, Redón J, Zanchetti A, Böhm M, 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). J Hypertens. 2013;31:1281–357.Google Scholar
  7. 7.
    Benetos A, Bulpitt CJ, Petrovic M, Ungar A, Agabiti Rosei E, Cherubini A, et al. An expert opinion from the european society of hypertension-european union geriatric medicine society working group on the management of hypertension in very old. Frail Subjects. Hypertension. 2016;67:820–5.Google Scholar
  8. 8.
    Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39:3021–104.Google Scholar
  9. 9.
    Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146–56.Google Scholar
  10. 10.
    Ferri C, Ferri L, Desideri G. Management of hypertension in the elderly and frail elderly. High Blood Press Cardiovasc Prev. 2017;24:1–11.Google Scholar
  11. 11.
    Lipsitz LA. Altered blood pressure homeostasis in advanced age: clinical and research implications. J Gerontol. 1989;44:M179–83.Google Scholar
  12. 12.
    Lakatta EG. Deficient neuroendocrine regulation of the cardiovascular system with advancing age in healthy humans. Circulation. 1993;87:631–6.Google Scholar
  13. 13.
    Chahal HS, Drake WM. The endocrine system and ageing. J Pathol. 2007;211:173–80.Google Scholar
  14. 14.
    Pietropaoli D, Ortu E, Severino M, Ciarrocchi I, Gatto R, Monaco A. Glycation and oxidative stress in the failure of dental implants: a case series. BMC Res Notes. 2013;6:296.Google Scholar
  15. 15.
    Pietropaoli D, Tatone C, D’Alessandro AM, Monaco A. Possible involvement of advanced glycation end products in periodontal diseases. Int J Immunopathol Pharmacol. 2010;23:683–91.Google Scholar
  16. 16.
    Pietropaoli D, Del Pinto R, Corridoni D, Rodriguez-Palacios A, Di Stefano G, Monaco A, et al. Occurrence of spontaneous periodontal disease in the SAMP1/YitFc murine model of Crohn disease. J Periodontol. 2014;85:1799–805.Google Scholar
  17. 17.
    Del Pinto R, Ferri C, Cominelli F. Vitamin D axis in inflammatory bowel diseases: role, current uses and future perspectives. Int J Mol Sci. 2017;18.  https://doi.org/10.3390/ijms18112360.
  18. 18.
    Shega JW, Dale W, Andrew M, Paice J, Rockwood K, Weiner DK. Persistent pain and frailty: a case for homeostenosis. J Am Geriatr Soc. 2012;60:113–7.Google Scholar
  19. 19.
    Yam AT, Lang EW, Lagopoulos J, Yip K, Griffith J, Mudaliar Y, et al. Cerebral autoregulation and ageing. J Clin Neurosci. 2005;12:643–6.Google Scholar
  20. 20.
    Peters R, Beckett N, Fagard R, Thijs L, Wang J-G, Forette F, et al. Increased pulse pressure linked to dementia: further results from the Hypertension in the Very Elderly Trial - HYVET. J Hypertens. 2013;31:1868–75.Google Scholar
  21. 21.
    Mossello E, Pieraccioli M, Nesti N, Bulgaresi M, Lorenzi C, Caleri V, et al. Effects of low blood pressure in cognitively impaired elderly patients treated with antihypertensive drugs. JAMA Intern Med. 2015;175:578–85.Google Scholar
  22. 22.
    de Leeuw FE, de Groot JC, Oudkerk M, Witteman JC, Hofman A, van Gijn J, et al. A follow-up study of blood pressure and cerebral white matter lesions. Ann Neurol. 1999;46:827–33.Google Scholar
  23. 23.
    Di Bari M, Pahor M, Franse LV, Shorr RI, Wan JY, Ferrucci L, et al. Dementia and disability outcomes in large hypertension trials: lessons learned from the systolic hypertension in the elderly program (SHEP) trial. Am J Epidemiol. 2001;153:72–8.Google Scholar
  24. 24.
    Tzourio C, Anderson C, Chapman N, Woodward M, Neal B, MacMahon S, et al. Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med. 2003;163:1069–75.Google Scholar
  25. 25.
    Forette F, Seux ML, Staessen JA, Thijs L, Birkenhäger WH, Babarskiene MR, et al. Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet. 1998;352:1347–51.Google Scholar
  26. 26.
    Weiner DE, Gaussoin SA, Nord J, Auchus AP, Chelune GJ, Chonchol M, et al. Cognitive Function and Kidney Disease: Baseline Data From the Systolic Blood Pressure Intervention Trial (SPRINT). Am J Kidney Dis. 2017;70:357–67.Google Scholar
  27. 27.
    van Sloten TT, Protogerou AD, Henry RMA, Schram MT, Launer LJ, Stehouwer CDA. Association between arterial stiffness, cerebral small vessel disease and cognitive impairment: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2015;53:121–30.Google Scholar
  28. 28.
    Georgakis MK, Synetos A, Mihas C, Karalexi MA, Tousoulis D, Seshadri S, et al. Left ventricular hypertrophy in association with cognitive impairment: a systematic review and meta-analysis. Hypertens Res. 2017;40:696–709.Google Scholar
  29. 29.
    Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis. 2003;41:1–12.Google Scholar
  30. 30.
    Chronic Kidney Disease Prognosis Consortium, Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet. 2010;375:2073–2081.Google Scholar
  31. 31.
    Bowling CB, Muntner P. Epidemiology of chronic kidney disease among older adults: a focus on the oldest old. J Gerontol A Biol Sci Med Sci. 2012;67:1379–86.Google Scholar
  32. 32.
    Nitsch D, Nonyane BAS, Smeeth L, Bulpitt CJ, Roderick PJ, Fletcher A. CKD and hospitalization in the elderly: a community-based cohort study in the United Kingdom. Am J Kidney Dis. 2011;57:664–72.Google Scholar
  33. 33.
    Hemmelgarn BR, Manns BJ, Lloyd A, James MT, Klarenbach S, Quinn RR, et al. Relation between kidney function, proteinuria, and adverse outcomes. JAMA. 2010;303:423–9.Google Scholar
  34. 34.
    Peters R, Beckett N, Poulter R, Burch L, Narkiewicz K, Fagard R, et al. Kidney function in the very elderly with hypertension: data from the hypertension in the very elderly (HYVET) trial. Age Ageing. 2013;42:253–8.Google Scholar
  35. 35.
    SPRINT Research Group, Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103–2116.Google Scholar
  36. 36.
    Del Pinto R, Pietropaoli D, Ferri C. Diastolic blood pressure and risk profile in renal and cardiovascular diseases. Results from the SPRINT trial. J Am Soc Hypertens. 2018;12(513–523):e3.Google Scholar
  37. 37.
    Goswami N, Blaber AP, Hinghofer-Szalkay H, Montani J-P. Orthostatic intolerance in older persons: etiology and countermeasures. Front Physiol. 2017;8:803.Google Scholar
  38. 38.
    Townsend RR, Chang TI, Cohen DL, Cushman WC, Evans GW, Glasser SP, et al. Orthostatic changes in systolic blood pressure among SPRINT participants at baseline. J Am Soc Hypertens. 2016;10:847–56.Google Scholar
  39. 39.
    Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res. 2011;21:69–72.Google Scholar
  40. 40.
    Fessel J, Robertson D. Orthostatic hypertension: when pressor reflexes overcompensate. Nat Clin Pract Nephrol. 2006;2:424–31.Google Scholar
  41. 41.
    Masaki KH, Schatz IJ, Burchfiel CM, Sharp DS, Chiu D, Foley D, et al. Orthostatic hypotension predicts mortality in elderly men: the Honolulu Heart Program. Circulation. 1998;98:2290–5.Google Scholar
  42. 42.
    Fedorowski A, Hedblad B, Engström G, Gustav Smith J, Melander O. Orthostatic hypotension and long-term incidence of atrial fibrillation: the Malmö Preventive Project. J Intern Med. 2010;268:383–9.Google Scholar
  43. 43.
    Eigenbrodt ML, Rose KM, Couper DJ, Arnett DK, Smith R, Jones D. Orthostatic hypotension as a risk factor for stroke: the atherosclerosis risk in communities (ARIC) study, 1987–1996. Stroke. 2000;31:2307–13.Google Scholar
  44. 44.
    Kario K, Eguchi K, Hoshide S, Hoshide Y, Umeda Y, Mitsuhashi T, et al. U-curve relationship between orthostatic blood pressure change and silent cerebrovascular disease in elderly hypertensives: orthostatic hypertension as a new cardiovascular risk factor. J Am Coll Cardiol. 2002;40:133–41.Google Scholar
  45. 45.
    Ricci F, Fedorowski A, Radico F, Romanello M, Tatasciore A, Di Nicola M, et al. Cardiovascular morbidity and mortality related to orthostatic hypotension: a meta-analysis of prospective observational studies. Eur Heart J. 2015;36:1609–17.Google Scholar
  46. 46.
    Zweifler AJ, Shahab ST. Pseudohypertension: a new assessment. J Hypertens. 1993;11:1–6.Google Scholar
  47. 47.
    Williamson JD, Supiano MA, Applegate WB, Berlowitz DR, Campbell RC, Chertow GM, et al. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥ 75 years: a randomized clinical trial. JAMA. 2016;315:2673–82.Google Scholar
  48. 48.
    Gangavati A, Hajjar I, Quach L, Jones RN, Kiely DK, Gagnon P, et al. Hypertension, orthostatic hypotension, and the risk of falls in a community-dwelling elderly population: the maintenance of balance, independent living, intellect, and zest in the elderly of Boston study. J Am Geriatr Soc. 2011;59:383–9.Google Scholar
  49. 49.
    Margolis KL, Palermo L, Vittinghoff E, Evans GW, Atkinson HH, Hamilton BP, et al. Intensive blood pressure control, falls, and fractures in patients with type 2 diabetes: the ACCORD trial. J Gen Intern Med. 2014;29:1599–606.Google Scholar
  50. 50.
    Foster-Dingley JC, Moonen JEF, de Ruijter W, van der Mast RC, van der Grond J. Orthostatic hypotension in older persons is not associated with cognitive functioning, features of cerebral damage or cerebral blood flow. J Hypertens. 2018;36:1201–6.Google Scholar
  51. 51.
    Agnoletti D, Valbusa F, Labat C, Gautier S, Mourad J-J, Benetos A, et al. Evidence for a prognostic role of orthostatic hypertension on survival in a very old institutionalized population. Hypertension. 2016;67:191–6.Google Scholar
  52. 52.
    Butt DA, Mamdani M, Austin PC, Tu K, Gomes T, Glazier RH. The risk of hip fracture after initiating antihypertensive drugs in the elderly. Arch Intern Med. 2012;172:1739–44.Google Scholar
  53. 53.
    Ruths S, Bakken MS, Ranhoff AH, Hunskaar S, Engesæter LB, Engeland A. Risk of hip fracture among older people using antihypertensive drugs: a nationwide cohort study. BMC Geriatr. 2015;15:153.Google Scholar
  54. 54.
    Xiao F, Qu X, Zhai Z, Jiang C, Li H, Liu X, et al. Association between loop diuretic use and fracture risk. Osteoporos Int. 2015;26:775–84.Google Scholar
  55. 55.
    Song HJ, Lee J, Kim Y-J, Jung S-Y, Kim HJ, Choi N-K, et al. β1 selectivity of β-blockers and reduced risk of fractures in elderly hypertension patients. Bone. 2012;51:1008–15.Google Scholar
  56. 56.
    Nijenhuis T, Vallon V, van der Kemp AWCM, Loffing J, Hoenderop JGJ, Bindels RJM. Enhanced passive Ca2+ reabsorption and reduced Mg2+ channel abundance explains thiazide-induced hypocalciuria and hypomagnesemia. J Clin Invest. 2005;115:1651–8.Google Scholar
  57. 57.
    LaCroix AZ, Ott SM, Ichikawa L, Scholes D, Barlow WE. Low-dose hydrochlorothiazide and preservation of bone mineral density in older adults. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2000;133:516–26.Google Scholar
  58. 58.
    Dvorak MM, De Joussineau C, Carter DH, Pisitkun T, Knepper MA, Gamba G, et al. Thiazide diuretics directly induce osteoblast differentiation and mineralized nodule formation by interacting with a sodium chloride co-transporter in bone. J Am Soc Nephrol. 2007;18:2509–16.Google Scholar
  59. 59.
    Ferri C, Del Pinto R. Diuretics. Reference module in biomedical sciences. Elsevier; 2018.  https://doi.org/10.1016/b978-0-12-801238-3.66129-9.
  60. 60.
    Bulpitt C, Fletcher A, Beckett N, Coope J, Gil-Extremera B, Forette F, et al. Hypertension in the very elderly trial (HYVET): protocol for the main trial. Drugs Aging. 2001;18:151–64.Google Scholar
  61. 61.
    Amery A, Birkenhäger W, Brixko P, Bulpitt C, Clement D, de Leeuw P, et al. Influence of antihypertensive drug treatment on morbidity and mortality in patients over the age of 60 years. European Working Party on High blood pressure in the Elderly (EWPHE) results: sub-group analysis on entry stratification. J Hypertens Suppl. 1986;4:S642–7.Google Scholar
  62. 62.
    Gueyffier F, Bulpitt C, Boissel JP, Schron E, Ekbom T, Fagard R, et al. Antihypertensive drugs in very old people: a subgroup meta-analysis of randomised controlled trials. INDANA Group. Lancet. 1999;353:793–6.Google Scholar
  63. 63.
    Warwick J, Falaschetti E, Rockwood K, Mitnitski A, Thijs L, Beckett N, et al. No evidence that frailty modifies the positive impact of antihypertensive treatment in very elderly people: an investigation of the impact of frailty upon treatment effect in the HYpertension in the Very Elderly Trial (HYVET) study, a double-blind, placebo-controlled study of antihypertensives in people with hypertension aged 80 and over. BMC Med. 2015;13:78.Google Scholar
  64. 64.
    Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhäger WH, 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.Google Scholar
  65. 65.
    Medical Research. Council trial of treatment of hypertension in older adults: principal results. MRC working party. BMJ. 1992;304:405–12.Google Scholar
  66. 66.
    Dahlöf B, Lindholm LH, Hansson L, Scherstén B, Ekbom T, Wester PO. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Lancet. 1991;338:1281–5.Google Scholar
  67. 67.
    Charlesworth CJ, Peralta CA, Odden MC. Functional status and antihypertensive therapy in older adults: a new perspective on old data. Am J Hypertens. 2016;29:690–5.Google Scholar
  68. 68.
    Pajewski NM, Williamson JD, Applegate WB, Berlowitz DR, Bolin LP, Chertow GM, et al. Characterizing frailty status in the systolic blood pressure intervention trial. J Gerontol A Biol Sci Med Sci. 2016;71:649–55.Google Scholar
  69. 69.
    JATOS Study Group. Principal results of the Japanese trial to assess optimal systolic blood pressure in elderly hypertensive patients (JATOS). Hypertens Res. 2008;31:2115–27.Google Scholar
  70. 70.
    Ogihara T, Saruta T, Rakugi H, Matsuoka H, Shimamoto K, Shimada K, et al. Target blood pressure for treatment of isolated systolic hypertension in the elderly: valsartan in elderly isolated systolic hypertension study. Hypertension. 2010;56:196–202.Google Scholar
  71. 71.
    Wei Y, Jin Z, Shen G, Zhao X, Yang W, Zhong Y, et al. Effects of intensive antihypertensive treatment on Chinese hypertensive patients older than 70 years. J Clin Hypertens. 2013;15:420–7.Google Scholar
  72. 72.
    Bavishi C, Bangalore S, Messerli FH. Outcomes of intensive blood pressure lowering in older hypertensive patients. J Am Coll Cardiol. 2017;69:486–93.Google Scholar
  73. 73.
    Benetos A, Labat C, Rossignol P, Fay R, Rolland Y, Valbusa F, et al. Treatment with multiple blood pressure medications, achieved blood pressure, and mortality in older nursing home residents: the PARTAGE study. JAMA Intern Med. 2015;175:989–95.Google Scholar
  74. 74.
    Stergiou GS, Boubouchairopoulou N, Kollias A. Measurement methodology: what does blood pressure mean in the PARTAGE study? JAMA Intern Med. 2015;175:1859–60.Google Scholar
  75. 75.
    Vidal-Petiot E, Ford I, Greenlaw N, Ferrari R, Fox KM, Tardif J-C, et al. Cardiovascular event rates and mortality according to achieved systolic and diastolic blood pressure in patients with stable coronary artery disease: an international cohort study. Lancet. 2016;388:2142–52.Google Scholar
  76. 76.
    Beddhu S, Chertow GM, Cheung AK, Cushman WC, Rahman M, Greene T, et al. Influence of baseline diastolic blood pressure on effects of intensive compared with standard blood pressure control. Circulation. 2018;137:134–43.Google Scholar
  77. 77.
    Ogliari G, Westendorp RGJ, Muller M, Mari D, Torresani E, Felicetta I, et al. Blood pressure and 10-year mortality risk in the Milan Geriatrics 75+ Cohort Study: role of functional and cognitive status. Age Ageing. 2015;44:932–7.Google Scholar
  78. 78.
    Kjeldsen SE, Stenehjem A, Os I, Van de Borne P, Burnier M, Narkiewicz K, et al. Treatment of high blood pressure in elderly and octogenarians: European Society of Hypertension statement on blood pressure targets. Blood Press. 2016;25:333–6.Google Scholar
  79. 79.
    Pietropaoli D, Del Pinto R, Ferri C, Wright JT Jr, Giannoni M, Ortu E, et al. Poor oral health and blood pressure control among US hypertensive adults: results from the National Health and Nutrition Examination Survey 2009 to 2014. Hypertension. 2018;72(6):1365–73.  https://doi.org/10.1161/HYPERTENSIONAHA.118.11528.Google Scholar
  80. 80.
    James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507–20.Google Scholar
  81. 81.
    Wright JT Jr, Fine LJ, Lackland DT, Ogedegbe G, Dennison Himmelfarb CR. Evidence supporting a systolic blood pressure goal of less than 150 mm Hg in patients aged 60 years or older: the minority view. Ann Intern Med. 2014;160:499–503.Google Scholar
  82. 82.
    Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure lowering on outcome incidence in hypertension: 4. Effects of various classes of antihypertensive drugs–overview and meta-analyses. J Hypertens. 2015;33:195–211.Google Scholar
  83. 83.
    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.Google Scholar
  84. 84.
    ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. 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.Google Scholar
  85. 85.
    Ezzati M, Lopez AD, Rodgers A, Vander Hoorn S, Murray CJL. Comparative Risk Assessment Collaborating Group. Selected major risk factors and global and regional burden of disease. Lancet. 2002;360:1347–60.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Life, Health and Environmental SciencesUniversity of L’Aquila, San Salvatore HospitalL’AquilaItaly

Personalised recommendations