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Effect of telmisartan/hydrochlorothiazide vs lisinopril/hydrochlorothiazide combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients

Journal of Human Hypertension volume 20, pages 177–185 (2006)Cite this article

Abstract

The aim of this study was to compare the effects of telmisartan/hydrochlorothiazide (HCTZ) vs lisinopril/HCTZ combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients. A total of 160 patients, 76 men and 84 women, aged 61–75 years, with sitting diastolic blood pressure (DBP) >90 mmHg and <110 mmHg and systolic blood pressure (SBP) >140 mmHg were randomized to receive temisartan 80 mg/HCTZ 12.5 mg o.d. or lisinopril 20 mg/HCTZ 12.5 mg o.d. for 24 weeks, according to a prospective, open-label, blinded end point, parallel-group design. At the end of a 2-week wash-out period and after 12 and 24 weeks of active treatment, 24-h noninvasive ambulatory BP monitoring (ABPM) was performed and cognitive function was evaluated through six different tests (verbal fluency, Boston naming test, word-list memory, word-list recall, word-list recognition and Trails B). Both treatments significantly reduced ambulatory BP. However, the telmisartan/HCTZ combination produced a greater reduction in 24-h, day-time and night time ABPM values. Lisinopril/HCTZ did not induce significant changes in any of the cognitive function test scores at any time of the study, whereas at both 12 and 24 weeks telmisartan/HCTZ significantly improved the word-list memory score (+17.1 and +15.7%, respectively, P<0.05 vs baseline), the word-list recall score (+13.5 and +16.9%, P<0.05) and the Trails B score (−33 and −30.5%, P<0.05). These results suggest that in elderly hypertensive patients treatment with telmisartan/HCTZ produces a slightly greater reduction in ambulatory BP than lisinopril/HCTZ combination and, unlike this latter, improves some of the components of cognitive function, particularly episodic memory and visuospatial abilities.

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References

  1. Skoog I, Lernfeldt B, Landahl S, Palmertz B, Andersson LA, Nilsson L et al. Fifteen-year longitudinal study of blood pressure and dementia. Lancet 1996; 34: 1141–1145.

    Article  Google Scholar 

  2. Launer LJ, Ross GW, Petrovitch H, Masaki K, Foley D, White LR et al. Midlife blood pressure and dementia: the Honolulu-Asia aging Study. Neurobiol Aging 2000; 21: 49–55.

    Article  CAS  PubMed  Google Scholar 

  3. Alves de Moraes S, Szklo M, Knopman D, Sato R . The relationship between temporal changes in blood pressure and changes in cognitive function. Atherosclerosis Risk in Communities (ARIC) Study. Prev Med 2002; 35: 258–263.

    Article  PubMed  Google Scholar 

  4. Farmer ME, Kittner SJ, Abbott RD, Wolz NM, White LR . Blood pressure and cognitive performance: the Framingham Study. Am J Epidemiol 1987; 126: 1103–1114.

    Article  CAS  PubMed  Google Scholar 

  5. Starr JM, Whalley LJH, Deary IJ . The effects of antihypertensive treatment on cognitive function: results from the HOPE Study. J Am Geriatr Soc 1996; 44: 411–415.

    Article  CAS  PubMed  Google Scholar 

  6. Prince MJ, Bird AS, Blizard RA, Mann AH . Is cognitive function of older patients affected by antihypertensive treatment? Results from the Medical Research Council's trial of hypertension in older adults. BMJ 1996; 312: 801–805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Forette F, Seux ML, Staessen JA, Thijs L, Birkenhager W . Prevention of dementia in randomized double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet 1998; 352: 1347–1351.

    Article  CAS  PubMed  Google Scholar 

  8. Guo Z, Fratiglioni L, Zhu L, Fastbom J, Winblad B, Viitanen M . Occurrence and progression of dementia in a community population aged 75 years and older: relationship of antihypertensive medication use. Arch Neurol 1999; 56: 991–996.

    Article  CAS  PubMed  Google Scholar 

  9. Gaard PR . The role of angiotensin II in cognition and behaviour. Eur J Pharmacol 2002; 438: 1–14.

    Article  Google Scholar 

  10. Culman J, Blume A, Gohlke P, Unger T . The renin–angiotensin system in the brain: possible therapeutic implications for AT1-receptor blockers. J Hum Hypertens 2002; 16: S64–S70.

    Article  CAS  PubMed  Google Scholar 

  11. Baranowska D, Braszko JJ, Wisniewski K . Effect of angiotensin II on acquisition and extinction of conditioned avoidance in rats. Psychopharmacology 1983; 81: 247–251.

    Article  CAS  PubMed  Google Scholar 

  12. Braszko JJ, Wisniewski K, Kupryszewski G, Witczuk B . Psychotropic effects of angiotensin II and angiotensin III in rat: locomotor and exploratory vs cognitive behaviour. Behav Brain Res 1987; 25: 195–203.

    Article  CAS  PubMed  Google Scholar 

  13. Barnes JM, Barnes NM, Costall B, Horovitz ZP, Naylor RJ . Angiotensin II inhibits the release of (3H) acetylcholine from the rat entorhinal cortex in vitro. Brain Res 1989; 492: 136–143.

    Article  Google Scholar 

  14. Vanhoutte PM . How to assess endothelial function in human blood vessels. J Hypertens 1999; 17: 1047–1058.

    Article  CAS  PubMed  Google Scholar 

  15. Barnes JM, Barnes NM, Costall B . Ace-inhibition and cognition. In Mc Gregor GA, Sever PS (eds). Current Advances in ACE-inhibition. Churchill-Livingstone: London, 1989, pp 159–171.

    Google Scholar 

  16. Mondadori C, Etienne P . Nootropic effects of ACE inhibitors in mice. Psychopharmacol 1990; 100: 301–307.

    Article  CAS  Google Scholar 

  17. Starr JM, Whalley LJ . ACE-inhibitors: Central Actions. Raven Press: New York, 1994.

    Google Scholar 

  18. Raghavendra V, Chopra K, Kulkarni SK . Comparative studies on the memory enhancing actions of captopril and losartan in mice using inhibitory shock avoidance paradigm. Neuropeptides 2001; 35: 65–69.

    Article  CAS  PubMed  Google Scholar 

  19. Tedesco MA, Ratti G, Mennella S, Manzo G, Grieco M, Rainone AC et al. Comparison of losartan and hydrochlorothiazide on cognitive function and quality of life in hypertensive patients. Am J Hypertens 1999; 12: 1130–1134.

    Article  CAS  PubMed  Google Scholar 

  20. Ebert U, Kirch W . Effects of captopril and enalapril on electroencephalogram and cognitive performance in healthy volunteers. Eur J Clin Pharmacol 1999; 55: 255–257.

    Article  CAS  PubMed  Google Scholar 

  21. Fogari R, Mugellini A, Zoppi A, Derosa G, Pasotti C, Fogari E et al. Influence of losartan and atenolol on cognitive function in very elderly hypertensive patients. J Hum Hypertens 2003; 17: 781–785.

    Article  CAS  PubMed  Google Scholar 

  22. Fogari R, Mugellini A, Zoppi A, Derosa G, Pasotti C, Fogari E et al. Effects of valsartan compared with enalapril on blood pressure and cognitive function in elderly patients with essential hypertension. Eur J Clin Pharmacol 2004; 59: 863–868.

    Article  CAS  PubMed  Google Scholar 

  23. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. JAMA 2003; 289: 2534–2573.

  24. 2003 European Society of Hypertension-European Society of Cardiology Guidelines for the management of arterial hypertension. J Hypertens 2003; 21: 1011–1053.

  25. Puschett JB . Diuretics. In: Oparil S, Weber MA (eds). Hypertension: A Companion to Brenner and Rector's The Kidney. W.B. Saunders Company: Philadelphia, 2000, pp 584–590.

    Google Scholar 

  26. Weber MA . Rationalizing the treatment of hypertension. Am J Hypertens 2001; 14: 3S–7S.

    Article  CAS  PubMed  Google Scholar 

  27. McClellan KJ, Markham A . Telmisartan. Drugs 1998; 56: 1039–1044.

    Article  CAS  PubMed  Google Scholar 

  28. Lancaster SG, Todd PA . Lisinopril. A preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in hypertension and congestive heart failure. Drugs 1988; 35: 646–669.

    Article  CAS  PubMed  Google Scholar 

  29. Starr JM, Whalley LJ . Senile hypertension and cognitive impairment. An overview. J Hypertens 1992; 10(Suppl): S31–S42.

    CAS  Google Scholar 

  30. Hansson L, Hedner T, Dahlof B . Prospective, randomized, open label, blinded-end point (PROBE) study: a novel design for intervention trials. Blood Press 1992; 1: 113–114.

    Article  CAS  PubMed  Google Scholar 

  31. Groppelli A, Omboni S, Ravogli A, Villani A, Parati G, Mancia G . Validation of the Spacelabs 90202 and 90297 devices for ambulatory blood pressure monitoring by comparison with intra-arterial resting and ambulatory measurements. J Hypertens 1991; 9(Suppl 3): S334–S335.

    CAS  Google Scholar 

  32. US Food and Drugs Administration. Proposed guidelines for the Clinical Evaluation of Antihypertensive Drugs. US Department of Health and Human Services, Division od Cardio-Renal Drug Products: Rockville, MD, 1988.

  33. Omboni S, Parati G, Zanchetti A, Mancia G . Calculation of trough: peak ratio of antihypertensive treatment from ambulatory blood pressure. Methodological aspects. J Hypertens 1995; 13: 1105–1112.

    Article  CAS  PubMed  Google Scholar 

  34. Parati G, Omboni S, Rizzoni D, Agabiti-Rosei E, Mancia G . The smoothness index: a new, reproducible and clinically relevant measure of the homogeneity of the blood pressure reduction with treatment for hypertension. J Hypertens 1998; 16: 1685–1691.

    Article  CAS  PubMed  Google Scholar 

  35. Isaacs B, Kennie AT . The SET test as an aid to the detection of dementia in old people. Br J psychiatr 1973; 123: 467–470.

    Article  CAS  Google Scholar 

  36. Tranel D . Neuropsychological assessment. Psychiatr Clin North Am 1992; 15: 283–299.

    Article  CAS  PubMed  Google Scholar 

  37. Kaplan EF, Goodglass H, Weinstraub S . The Boston naming test. Veterans Administration Medical Center: Boston, 1978.

  38. Morris JC, Mohs RC, Rogers H, Fillenbaum G, Heyman A . Consortium to establish a registry for Alzheimer's disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease. Neurology 1989; 39: 1159–1165.

    Article  CAS  PubMed  Google Scholar 

  39. Mohs RC, Kim Y, Johus CA . Assessing change in Alzheimer's disease: memory and language tests. In: Poon LW (ed). Handbook for Clinical Memory Assessment of Older Adults. American Psychological Association: Washington, 1986, pp 149–155.

    Chapter  Google Scholar 

  40. Reitan R . validity of the Trail Making Test as an indicator of organic brain damage. Percept Mot Skills 1958; 8: 271–276.

    Article  Google Scholar 

  41. White WB . Blood pressure load and target organ effects in patients with essential hypertension. J Hypertens 1991; 9(Suppl 8): S39–S41.

    CAS  Google Scholar 

  42. Squire LR . Memory and Brain. Oxford University Press: Oxford, 1987.

    Google Scholar 

  43. Cabeza R, Nyberg L . Imaging cognition: an empirical review of PET studies with normal subjects. J Cogn Neurosci 1997; 9: 1–26.

    Article  CAS  PubMed  Google Scholar 

  44. Fahlander K, Wahlin A, Fastbom J, Grut M, Forsell Y, Hill R et al. The relationship between signs of cardiovascular deficiency and cognitive performance in old age: a population based study. J Gerontol B Psychol Sci Soc Sci 200; 55: P259–P265.

    Article  Google Scholar 

  45. Backman L, Small B, Wahlin A, Larsson M . Cognitive functioning in very old age. In: Cruik FIM, Salthouse TA (eds). The Handbook of Aging and Cognition, 2nd edn. Erlbaum: Muhwah, NJ, pp 499–558.

  46. Raghawendra V, Chopra K, Kulkarni SK . Comparative studies of the memory-enhancing actions of captopril and losartan in mice using inhibitory shock avoidance in mice using inhibitory shock avoidance paradigm. Neuropeptides 2001; 35: 65–69.

    Article  Google Scholar 

  47. Barnes NM, Champaneria S, Costall B, Kelly ME, Murphy DA . Cognitive enhancing actions of DuP 753 detected in a mouse habituation paradigm. Neuroreport 1990; 1: 239–242.

    Article  CAS  PubMed  Google Scholar 

  48. Okuyama S, Sakagawa T, Inagami T . Role of the ang II type 2 receptors in the mouse central nervous system. Jpn J Pharmacol 1999; 81: 259–263.

    Article  CAS  PubMed  Google Scholar 

  49. Wright JW, Stubley LA, Pederson ES, Kramar EA, Hanesworth J, Harding JW . Contributions of the brain angiotensin IV-AT4 receptor subtype system to spatial learning. J Neurosci 1999; 19: 3952–3961.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Pederson ES, Krishnan R, Harding JW, Wright JW . A role for the angiotensin AT4 receptor subtype in overcoming scopolamine-induced spatial memory deficits. Regul Pept 2001; 102: 147–156.

    Article  CAS  PubMed  Google Scholar 

  51. Goldstein G, Materson BJ, Cushman WC, Reda DJ, Freis ED, Ramirez EA et al. Treatment of hypertension in the elderly(II): cognitive and behavioural function. Hypertension 1990; 15: 361–369.

    Article  CAS  PubMed  Google Scholar 

  52. Vanmolkot FHM, DeHoon JNJN, Van de Ven LLM, Van Bortel LMAB . Impact of antihypertensive treatment on quality of life: comparison between bisoprolol and bendrofluazide. J Hum Hypertens 1999; 13: 559–563.

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Internal Medicine and Therapeutics, Clinica Medica II, IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy

    R Fogari, A Mugellini, A Zoppi, P Lazzari, M Destro, A Rinaldi & P Preti

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  1. R Fogari
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  2. A Mugellini
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Correspondence to R Fogari.

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Fogari, R., Mugellini, A., Zoppi, A. et al. Effect of telmisartan/hydrochlorothiazide vs lisinopril/hydrochlorothiazide combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients. J Hum Hypertens 20, 177–185 (2006). https://doi.org/10.1038/sj.jhh.1001964

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  • DOI: https://doi.org/10.1038/sj.jhh.1001964

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