Антигипертензивные препараты в профилактике когнитивных нарушений и деменции: фокус на антагонисты кальция и диуретики

Артериальная гипертония ассоциирована с повышенным риском снижения когнитивных функций и развития сосудистой деменции и болезни Альцгеймера. В этом контексте антигипертензивная терапия может иметь профилактический эффект. Представленные в настоящем обзоре литературные данные свидетельствуют о том, что, несмотря на наличие некоторых противоречий в результатах исследований, антигипертензивные препараты, особенно дигидропиридиновые антагонисты кальция, диуретики и некоторые блокаторы ренин-ангиотензин-альдостероновой системы, обладают церебропротективными свойствами, причем не только за счет снижения артериального давления, но также и посредством дополнительных специфических нейропротективных механизмов. Это позволяет рассматривать антагонисты кальция и диуретики в качестве важного компонента лечения артериальной гипертонии, в т.ч. у пациентов пожилого и старческого возрастов, для профилактики снижения когнитивных функций и развития разных типов деменции.

Нитрендипин среди антагонистов кальция и индапамид среди диуретиков обладают наибольшей доказательной базой, свидетельствующей о наличии у них выраженных церебропротективных свойств.

1. Яхно Н. Н., Захаров В. В., Локшина А. Б. и др. Деменции: руководство для врачей. М. : МЕДпресс-информ; 2011. 264 с. ISBN 978-5-98322-723-1.

2. Дамулин И. В. Когнитивные расстройства. Некоторые вопросы клиники, диагностики, лечения. М.; 2012. 19 с.

3. Rouch L, Cestac P, Hanon O, et al. Antihypertensive Drugs, Prevention of Cognitive Decline and Dementia: A Systematic Review of Observational Studies, Randomized Controlled Trials and Meta-Analyses, with Discussion of Potential Mechanisms. CNS Drugs. 2015;29(2):113-30. https://doi.org/10.1007/s40263-015-0230-6.

4. Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005;366(9503):2112-7 https://doi.org/10.1016/S0140-6736(05)67889-0.

5. Viswanathan A, Rocca WA, Tzourio C. Vascular risk factors and dementia: how to move forward? Neurology. 2009;72(4):368-74. https://doi.org/101212/01.wnl.0000341271.90478.8e.

6. б. Qiu C, Winblad B, Fratiglioni L. The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol. 2005;4(8):487-99. https://doi.org/101016/S1474-4422(05)70141-1.

7. Iadecola C, Yaffe K, Biller J, et al. Impact of Hypertension on Cognitive Function: A Scientific Statement From the American Heart Association. Hypertension. 2016;68(6):e67-94. https://doi.org/10.1161/HYP.0000000000000053.

8. Рекомендации по лечению артериальной гипертонии. ESH/ESC 2013. Российский кардиологический журнал. 2014;19(1):7-94. https://doi.org/10.1093/euroheartj/eht151.

9. Fournier A, Oprisiu-Fournier R, Serot JM, et al. Prevention of dementia by antihypertensive drugs: how AT1-receptor-blockers and dihydropyridines better prevent dementia in hypertensive patients than thiazides and ACE-inhibitors. Expert Rev Neurother. 2009;9(9):1413-31. https://doi.org/10.1586/ern.09.89.

10. Shah K, Qureshi S, Johnson M, et al. Does use of antihypertensive drugs affect the incidence or progression of dementia? A systematic review. Am J Geriatr Pharmacother. 2009;7(5):250-61. https://doi.org/10.1016/j.amjopharm.2009.11.001.

11. Tzourio C, Dufouil C, Ducimetiere P, et al. Cognitive decline in individuals with high blood pressure: a longitudinal study in the elderly. EVA Study Group. Epidemiology of vascular aging. Neurology. 1999;53(9):1948-52.

12. Hajjar I, Catoe H, Sixta S, et al. Cross-sectional and longitudinal association between antihypertensive medications and cognitive impairment in an elderly population. J Gerontol A Biol Sci Med Sci. 2005;60(1):67-73.

13. Qiu C, von Strauss E, Fastbom J, et al. Low blood pressure and risk of dementia in the Kungsholmen project: a 6-year follow-up study. Arch Neurol. 2003;60(2):223-8.

14. Khachaturian AS, Zandi PP, Lyketsos CG, et al. Antihypertensive medication use and incident Alzheimer disease: the Cache County Study. Arch Neurol. 2006;63(5):686-92. https://doi.org/10.1001/archneur.63.5.noc60013.

15. Peila R, White LR, Masaki K, et al. Reducing the risk of dementia: efficacy of 39. long-term treatment of hypertension. Stroke. 2006;37(5):1165-70. https://doi.org/10.1161/01.STR.0000217653.01615.93.

16. Li N-C, Lee A, Whitmer RA, et al. Use of angiotensin receptor blockers and risk of 40. dementia in a predominantly male population: prospective cohort analysis. BMJ. 2010;340:b5465. https://doi.org/10.1136/bmj.b5465.

17. Johnson ML, Parikh N, Kunik ME, et al. Antihypertensive drug use and the risk of 41. dementia in patients with diabetes mellitus. Alzheimers Dement. 2012;8(5):437-44. https://doi.org/10.1016/j.jalz.2011.05.2414.

18. Yasar S, Xia J, Yao W, et al. Antihypertensive drugs decrease risk of Alzheimer 42. disease: Ginkgo Evaluation of Memory Study. Neurology. 2013;81(10):896-903. https://doi.org/10.1212/WNL.0b013e3182a35228.

19. Haag MDM, Hofman A, Koudstaal PJ, et al. Duration of antihypertensive drug use 43. and risk of dementia: a prospective cohort study. Neurology. 2009;72(20):1727-34. https://doi.org/10.1212/01.wnl.0000345062.86148.3f.

20. In't Veld BA, Ruitenberg A, Hofman A, et al. Antihypertensive drugs and incidence of 44. dementia: the Rotterdam Study. Neurobiol Aging. 2001;22(3):407-12.

21. Chiu WC, Ho WC, Lin MH, et al. Angiotension receptor blockers reduce the risk of dementia. J Hypertens. 2014;32(4):938-47 https://doi.org/10.1097/HJH.0000000000000086.

22. Morris MC, Scherr PA, Hebert LE, et al. Association of incident Alzheimer disease and blood pressure measured from 13 years before to 2 years after diagnosis in a large community study. Arch Neurol. 2001;58(10):1640-6.

23. Lindsay J, Laurin D, Verreault R, et al. Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging. Am J Epidemiol. 2002;156(5):445-53.

24. Yasar S, Corrada M, Brookmeyer R, et al. Calcium channel blockers and risk of AD: the Baltimore Longitudinal Study of Aging. Neurobiol Aging. 2005;26(2): 157-63. https://doi.org/10.1016/j.neurobiolaging.2004.03.009.

25. Bosch J, Yusuf S, Pogue J, et al. Use of ramipril in preventing stroke: double blind randomized trial. BMJ. 2002;324(7339):699-702

26. Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme 49. inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342(3):145-53. https://doi.org/10.1056/NEJM200001203420301.

27. Tzourio C, Anderson C, Chapman N, 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(9):1069-75. https://doi.org/10.1001/archinte.163.9.1069.

28. Medical Research Council trial of treatment of hypertension in older adults: principal results. MRC Working Party. BMJ. 1992;304(6824):405-12.

29. Prince MJ, Bird AS, Blizard RA, et al. Is the cognitive function of older patients 52. affected by antihypertensive treatment? Results from 54 months of the Medical Research Council's trial of hypertension in older adults. BMJ. 1996;312(7034):801-5.

30. Lithell H, Hansson L, Skoog I, et al. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J 53. Hypertens. 2003;21(5):875-86. https://doi.org/10.1097/01.hjh.0000059028.82022.89.

31. 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(18):1887-98. https://doi.org/10.1056/NEJMoa0801369.

32. Peters R, Beckett N, Forette F, et al. Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial. Lancet Neurol. 2008;7(8):683-9. https://doi.org/10.1016/S1474-4422(08)70143-1.

33. Diener HC, Sacco RL, Yusuf S, et al. Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study. Lancet Neurol. 2008;7(10):875-84. https://doi.org/10.1016/S1474-4422(08)70198-4.

34. Anderson C, Teo K, Gao P, et al. Renin-angiotensin system blockade and cognitive function in patients at high risk of cardiovascular disease: analysis of data from the ONTARGET and TRANSCEND studies. Lancet Neurol. 2011;10(1):43-53. https://doi.org/10.1016/S1474-4422(10)70250-7.

35. 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(24):3255-64.

36. Applegate WB, Pressel S, Wittes J, et al. Impact of the treatment of isolated systolic hypertension on behavioral variables. Results from the systolic hypertension in the elderly program. Arch Intern Med. 1994;154(19):2154-60.

37. 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(9080):757-64.

38. Forette F, Seux M-L, Staessen JA, et al. The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study. Arch Intern Med. 2002;162(18):2046-52.

39. Levi Marpillat N, Macquin-Mavier I, Tropeano AI, et al. Antihypertensive classes, cognitive decline and incidence of dementia: a network meta-analysis. J Hypertens. 2013;31(6):1073-82. https://doi.org/10.1097/HJH.0b013e3283603f53.

40. Yasar S, Schuchman M, Peters J, et al. Relationship Between Antihypertensive Medications and Cognitive Impairment: Part I. Review of Human Studies and Clinical Trials. Curr Hypertens Rep. 2016;18(8):67. https://doi.org/10.1007/s11906-016-0674-1.

41. Peters R, Collerton J, Granic A, et al. Antihypertensive drug use and risk of cognitive decline in the very old: an observational study - the Newcastle 85+ Study. J Hypertens. 2015;33(10):2156-64. https://doi.org/10.1097/HJH.0000000000000653.

42. Chuang YF, Breitner JCS, Chiu YL, et al. Use of diuretics is associated with reduced risk of Alzheimer's disease. The Cache County Study. Neurobiol Aging. 2014;35(11):2429-35. https://doi.org/10.1016/j.neurobiolaging.2014.05.002.

43. Wagner G, Icks A, Abholz HH, et al. Antihypertensive treatment and risk of dementia: a retrospective database study. Int J Clin Pharmacol Ther. 2012;50(3):195-201. https://doi.org/10.5414/CP201284.

44. Gelber R, Ross G, Petrovitch H, et al. Antihypertensive medication use and risk of cognitive impairment. The Honolulu-Asia Aging Study Neurology. 2013;81:888-95. https://doi.org/10.1212/WNL.0b013e3182a351d4.

45. Tully PJ, Hanon O, Cosh S, et al. Diuretic antihypertensive drugs and incident dementia risk: a systematic review, meta-analysis and meta-regression of prospective studies. J Hypertens. 2016;34(6):1027-35. https://doi.org/10.1097/HJH.0000000000000868.

46. Davies N, Kehoe P, Shlomo YB, et al. Associations of anti-hypertensive treatments with Alzheimer's disease, vascular dementia, and other dementias. J Alzheimers Dis. 2014;26(4):699-708. https://doi.org/10.3233/JAD-2011-110347.

47. Solfrizzi V, Scafato E, Frisardi V, et al. Angiotensin-converting enzyme inhibitors and incidence of mild cognitive impairment. The Italian Longitudinal Study on Aging. Age (Dordr). 2013;35(2):441-53. https://doi.org/10.1007/s11357-011-9360-z.

48. Hsu CY, Huang CC, Chan WL, et al. Angiotensin-receptor blockers and risk of Alzheimer's disease in hypertension population-a nationwide cohort study. Circ J. 2013;77(2):405-10. https://doi.org/10.1253/circj.CJ-12-0658.

49. Wu CL, Wen SH. A 10-year follow-up study of the association between calcium channel blocker use and the risk of dementia in elderly hypertensive patients. Medicine (Baltimore). 2016;95(32):e4593. https://doi.org/10.1097/MD.0000000000004593.

50. Hussain S, Singh A, Rahman SO, et al. Calcium channel blocker use reduces incident dementia risk in elderly hypertensive patients: A meta-analysis of prospective studies. Neurosci Lett. 2018;671:120-7. https://doi.org/10.1016/j.neulet.2018.02.027.

51. Peters J, Booth A, Peters R. Potential for specific dihydropyridine calcium channel blockers to have a positive impact on cognitive function in humans: a systematic review. Ther Adv Chronic Dis. 2015;6(4):160-9. https://doi.org/10.1177/2040622315582353.

52. Patel A, MacMahon S, Chalmers J, et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007; 370(9590):829-40. https://doi.org/10.1016/S0140-6736(07)61303-8.

53. Rastas S, Pirttila T, Mattila K, et al. Vascular risk factors and dementia in the general population aged >85 years. Prospective population-based study. Neurobiol Aging. 2010;31(1):1-7 https://doi.org/10.1016/j.neurobiolaging.2008.02.020.

54. Guo Z, Fratiglioni L, Zhu L, et al. Occurrence and progression of dementia in a community population aged 75 years and older: relationship of antihypertensive medication use. Arch Neurol. 1999;56(8):991-6.

55. Ohrui T, Matsui T, Yamaya M, et al. Angiotensin-converting enzyme inhibitors and incidence of Alzheimer's disease in Japan. J Am Geriatr Soc. 2004;52(4):649-50. https://doi.org/10.1111/j.1532-5415.2004.52178_7.x.

56. Vascular factors and risk of dementia: design of the Three-City Study and baseline characteristics of the study population. Neuroepidemiol. 2003;22(6):316-25. https://doi.org/10.1159/000072920.

57. Corrada MM, Brookmeyer R, Paganini-Hill A, et al. Dementia incidence continues to increase with age in the oldest old the 90^ study. Ann Neurol. 2010 ;67(1):114-21. https://doi.org/10.1002/ana.21915.

58. Hainsworth AH, Markus HS. Do in vivo experimental models reflect human cerebral small vessel disease? A systematic review. J Cereb Blood Flow Metab. 2008;28(12):1877-91. https://doi.org/10.1038/jcbfm.2008.91.

59. Liao D, Cooper L, Cai J, et al. Presence and severity of cerebral white matter lesions and hypertension, its treatment, and its control. The ARIC Study. Atherosclerosis Risk in Communities Study. Stroke. 1996;27(12):2262-70.

60. Suter OC, Sunthorn T, Kraftsik R, et al. Cerebral hypoperfusion generates cortical watershed microinfarcts in Alzheimer disease. Stroke. 2002 ;33(8):1986-92.

61. Pasquier F, Leys D. Why are stroke patients prone to develop dementia? J Neurol. 1997;244(3):135-42.

62. Hardy JA, Mann DM, Wester P, et al. An integrative hypothesis concerning the pathogenesis and progression of Alzheimer's disease. Neurobiol Aging. 1986;7(6):489-502.

63. Zhang X, Zhou K, Wang R, et al. Hypoxia-inducible factor 1alpha (HIF-1alpha)-mediated hypoxia increases BACE1 expression and beta-amyloid generation. J Biol Chem. 2007;282(15):10873-80. https://doi.org/10.1074/jbc.M608856200.

64. Iadecola C, Park L, Capone C. Threats to the mind: aging, amyloid, and hypertension. Stroke. 2009;40(3 Suppl):S40-4. https://doi.org/10.1161/STROKEAHA.108.533638.

65. Angeli F, Verdecchia P, Reboldi GP, et al. Calcium channel blockade to prevent stroke in hypertension: a meta-analysis of 13 studies with 103.793 subjects. Am J Hypertens. 2004;17(9):817-22. https://doi.org/10.1016/j.amjhyper.2004.06.002.

66. Lopez-Arrieta JM, Birks J. Nimodipine for primary degenerative, mixed and vascular dementia. Cochrane Database Syst Rev. 2002;3:CD000147. https://doi.org/10.1002/14651858.CD000147.

67. Berridge MJ. Calcium signalling and Alzheimer’s disease. Neurochem Res. 2011;36(7):1149-56. https://doi.org/10.1007/s11064-010-0371-4.

68. Thibault O, Gant JC, Landfield PW. Expansion of the calcium hypothesis of brain aging and Alzheimer’s disease: minding the store. Aging Cell. 2007;6(3):307-17. https://doi.org/10.1111/j.1474-9726.2007.00295.x.

69. Thibault O, Landfield PW. Increase in single L-type calcium channels in hippocampal neurons during aging. Science. 1996;272(5264):1017-20.

70. Pierrot N, Ghisdal P, Caumont AS, et al. Intraneuronal amyloid-beta1-42 production triggered by sustained increase of cytosolic calcium concentration induces neuronal death. J Neurochem. 2004;88(5):1140-50.

71. Querfurth HW, Selkoe DJ. Calcium ionophore increases amyloid beta peptide production by cultured cells. Biochemistry (Mosc). 1994;33(15):4550-61.

72. Mattson MP. Antigenic changes similar to those seen in neurofibrillary tangles are elicited by glutamate and Ca2+ influx in cultured hippocampal neurons. Neuron. 1990;4(1):105-17.

73. Nixon RA. The calpains in aging and aging-related diseases. Ageing Res Rev. 2003;2(4):407-18.

74. Green KN, LaFerla FM. Linking calcium to Abeta and Alzheimer’s disease. Neuron. 2008;59(2):190-4. https://doi.org/10.1016/j.neuron.2008.07.013.

75. Kuchibhotla KV, Goldman ST, Lattarulo CR, et al. Abeta plaques lead to aberrant regulation of calcium homeostasis in vivo resulting in structural and functional disruption of neuronal networks. Neuron. 2008;59(2):214-25. https://doi.org/10.1016/j.neuron.2008.06.008.

76. Yu JT, Chang RCC, Tan L. Calcium dysregulation in Alzheimer’s disease: from mechanisms to therapeutic opportunities. Prog Neurobiol. 2009;89(3):240-55. https://doi.org/10.1016/j.pneurobio.2009.07.009.

77. Mattson MP. Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives. Physiol Rev. 1997;77(4):1081-132. https://doi.org/10.1152/physrev.1997.77.4.1081.

78. Furukawa K, Wang Y, Yao PJ, et al. Alteration in calcium channel properties is responsible for the neurotoxic action of a familial frontotemporal dementia tau mutation. J Neurochem. 2003;87(2):427-36.

79. Trompet S, Westendorp RGJ, Kamper AM, et al. Use of calcium antagonists and cognitive decline in old age. The Leiden 85-plus study. Neurobiol Aging.

80. ;29(2):306-8. https://doi.org/10.1016/j.neurobiolaging.2006.10.006.

81. Lu N, Dubreuil M, Zhang Y, et al. Gout and the risk of Alzheimer’s disease: a population-based, BMI-matched cohort study. Ann Rheum Dis. 2016;75(3):547-51. https://doi.org/10.1136/annrheumdis-2014-206917.

82. Euser SM, Hofman A, Westendorp RG, et al. Serum uric acid and cognitive function and dementia. Brain. 2009;132(Pt 2):377-82. https://doi.org/10.1093/brain/awn316.

83. Al-khateeb E, Althaher A, Al-khateeb M, et al. Relation between uric acid and Alzheimer’s disease in elderly Jordanians. J Alzheimers Dis. 2015;44(3):859-65. https://doi.org/10.3233/JAD-142037.

84. Reyes AJ. Heart failure, dementia, and diuretics: is uric acid involved? Arch Intern Med. 2006;166(20):2286. https://doi.org/10.1001/archinte.166.20.2286.

85. Hernandorena I, Duron E, Vidal JS, et al. Treatment options and considerations for hypertensive patients to prevent dementia. Exp Opin Pharmacother. 2017;18(10):989-1000. https://doi.org/10.1080/14656566.2017.1333599

86. Syrov AV, Sturov NV. Patient of senile age with arterial hypertension in outpatient treatment. Clinical Gerontology. 2018;3-4:28-34. (In Russ.) https://doi.org/10.26347/1607-2499201803-04028-034.

87. Liu L, Wang JG, Gong L, et al. Comparison of active treatment and placebo for older Chinese patients with isolated systolic hypertension. Systolic Hypertension in China (Syst-China) Collaborative Group. J Hypertens. 1998;16(12Pt 1):1823-9.

88. Ткачева О.Н., Рунихина Н. К., Котовская Ю. В. и др. Лечение артериальной гипертонии у пациентов 80 лети старше и пациентов со старческой астенией. Кардиоваскулярная терапия и профилактика. 2017;16(1):8-21. https://doi.org/10.15829/1728-8800-2017-1-8-21.

89. Bachmeier C, Beaulieu-Abdelahad D, Mullan M, et al. Selective dihydropyiridine compounds facilitate the clearance of p-amyloid across the blood-brain barrier. Eur J Pharmacol. 2011;659(2-3):124-9. https://doi.org/10.1016/j.ejphar.2011.03.048.

90. Paris D, Bachmeier C, Patel N, et al. Selective antihypertensive dihydropyridines lower Ap accumulation by targeting both the production and the clearance of Ap across the blood-brain barrier. Mol Med. 2011; 17(3-4): 149-62. https://doi.org/10.2119/molmed.2010.00180.

91. Преображенский Д. В., Сидоренко Б. А., Шатунова И. М. и др. Тиазидные и тиазидоподобные диуретики как краеугольный камень современной антигипертензивной терапии. Российский кардиологический журнал. 2004;9(4):5-13.

92. Карпов Р.С., Мордовин В. Ф. Хронические формы цереброваскулярной патологии у больных артериальной гипертонией: частота выявления, динамика развития, особенности терапии. Болезни сердца и сосудов. 2006;1(3):17-21.

93. Lu M, Ma L, Wang X, et al. Indapamide suppresses amyloid-p production in cellular models of Alzheimer's disease through regulating BACE1 activity. Int J Clin Exp Med. 2017;10(4):5922-30.

94. Chillon JM, Baumbach GL. Effects of indapamide, a thiazide-like diuretic, on structure of cerebral arterioles in hypertensive rats. Hypertension. 2004;43(5):1092-7. https://doi.org/10.1161/01.HYP.0000122874.21730.81.

95. Nishioku T, Takata F, Yamauchi A, et al. Protective Action of Indapamide, a ThiazideLike Diuretic, on Ischemia-Induced Injury and Barrier Dysfunction in Mouse Brain Microvascular Endothelial Cells. J Pharmacol Sci. 2007;103(3):323-7 https://doi.org/10.1254/jphs.SC0060222.

96. Марцевич С. Ю., Кутишенко Н.П., Деев А. Д. и др. Изучение эффективности и переносимости препарата Индап в сравнении с препаратами Арифон и Арифон Ретард у больных мягкой и умеренной артериальной гипертонией, назначаемых как в виде монотерапии, так и в комбинации с ингибиторами АПФ. Многоцентровое, открытое, рандомизированное перекрестное исследование. Российский кардиологический журнал. 2006;11(2):73-7