Daily profile of arterial pressure and brain microstructural changes in patients with hypertension-related cerebral small vessel disease

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Introduction. Application of modern antihypertensive medications has improved the course of arterial hypertension (AH), but has not led to the expected decrease
in small vessel disease (SVD) incidence and its complications. This fact encourages further investigation of hypertension-related mechanisms of brain damage.
Objective: to study the relation between daily profile of blood pressure and brain microstructure changes in patients with both SVD and AH.
Material and methods. The study included 64 patients (38 – 59.4%) female, mean age 59.4±5.4 years) with both SVD and AH. Ambulatory blood pressure
monitoring and diffusion-tensor MRI were obtained for all participants. The relation between studied parameters was estimated using the multivariate statistical
analysis method – linear regression analysis.
Results. Сhanges in daily profile of blood pressure according to ambulatory blood pressure monitoring data was associated with microstructure abnormalities of
the juxtacortical white matter hyperintensities (jWMH) of anterior frontal lobes, temporal-parietal regions and left posterior cingulate cortex. An increase and
variability of diastolic blood pressure were of primary importance in brain microstructural damage in mentioned areas leading to mean diffusivity and radial
diffusivity increase.
Conclusion. The revealed relation between daily profile of blood pressure and brain microstructural changes indicating increase of free water diffusivity and
myelin damage in jWMH and posterior cingulate cortex corresponds to the experimental data on the breakdown of the autoregulation reaction in cortex arteries
and further increase of brain-blood barrier permeability with descending vasogenic edema in brain damage in hypertensive patients. An increase and variability of
diastolic blood pressure have primary importance to microstructural damage of white matter in patients with SVD receiving antihypertensive treatment.

About the authors

Larisa A. Dobrynina

Research Center of Neurology

Author for correspondence.
Email: dobrla@mail.ru
ORCID iD: 0000-0001-9929-2725

D. Sci. (Med.), Head, 3rd Neurology department

Russian Federation, Moscow

Kamila V. Shamtieva

Research Center of Neurology

Email: dobrla@mail.ru
Russian Federation, Moscow

Еlena I. Kremneva

Research Center of Neurology

Email: dobrla@mail.ru
Russian Federation, Moscow

Lyudmila A. Kalashnikova

Research Center of Neurology

Email: dobrla@mail.ru
Russian Federation, Moscow

Marina V. Krotenkova

Research Center of Neurology

Email: dobrla@mail.ru
ORCID iD: 0000-0003-3820-4554

D. Sci. (Med.), Head, Neuroradiology department

Russian Federation, 125367 Moscow, Volokolamskoye shosse, 80

Elena V. Gnedovskaya

Research Center of Neurology

Email: dobrla@mail.ru
Russian Federation, Moscow

Aleksandr B. Berdalin

M.V. Lomonosov Moscow State University

Email: dobrla@mail.ru
Russian Federation, Moscow


  1. Wardlaw J.M., Smith C., Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol 2013; 12: 483–497. doi: 10.1016/S1474-4422(13)70060-7. PMID: 23602162.
  2. Liu Y., Dong Y.H., Lyu P.Y. et al. Hypertension-induced cerebral small vessel disease leading to cognitive impairment. Chin Med J 2018; 131: 615–619. doi: 10.4103/0366-6999.22606. PMID: 29483399.
  3. Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 2010; 9: 689–701. doi: 10.1016/S1474-4422(10)70104-6. PMID: 20610345.
  4. Maksudov G.A., Shmidt E.V. (eds.) [Dyscirculatory encephalopathy. Vascular diseases of the brain]. Moscow: Meditsina, 1975. (In Russ.)
  5. Gannushkina I.V., Lebedeva N.V. [Hypertensive encephalopathy]. Moscow: Meditsina, 1987. (In Russ.)
  6. Gulevskaya T.S., Lyudkovskaya I.G. [Arterial hypertension and pathology of the white matter of the brain]. Arhiv patologii 1992; 2: 33–59. (In Russ.)
  7. Gulevskaya T.S., Morgunov V.A. [Pathological anatomy of cerebral circulatory disorders in atherosclerosis and arterial hypertension]. Moscow: Meditsina, 2009. (In Russ.)
  8. Kalashnikova L.A., Gulevskaya T.S., Kadykov A.S. et al. [Subcortical arteriosclerotic encephalopathy (clinical and morphological study)]. Nevrologicheskiy zhurnal 1992; 2: 7–13. (In Russ.)
  9. Kulov B.B., Kalashnikova L.A. [The circadian rhythm of blood pressure in patients with subcortical arteriosclerotic encephalopathy]. Nevrologicheskiy zhurnal 2003; 8(3): 14–17. (In Russ.)
  10. Kadykov A.S., Manvelov L.S., Shahparonova N.V. [Chronic vascular diseases of the brain]. Moscow: GEOTAR-Media, 2006. (In Russ.)
  11. Suslina Z.A., Geraskina L.A., Fonyakin A.V. [Arterial hypertension, vascular pathology of the brain and antihypertensive treatment]. Moscow: Mediagraphics, 2006. (In Russ.)
  12. Tanashyan M.M., Maksimova M.Yu., Domashenko M.A. [Dyscirculatory encephalopathy. A guide to medical appointment]. Terapevticheskiy spravochnik 2015; 2: 1–25. (In Russ.)
  13. Suslina Z.A., Geraskina L.A., Fonyakin A.V. [Actual questions and rational approach to the treatment of arterial hypertension in the vascular pathology of the brain]. Kardiovaskulyarnaya terapiya i profilaktika 2005; 4(3): 82–87. (In Russ.)
  14. Geraskina L.A. [Chronic cerebrovascular diseases in arterial hypertension: blood supply to the brain, central hemodynamics and functional vascular reserve: med. sci. diss.]. Moscow, 2008. (In Russ.)
  15. Konovalov R.N. [Neurovisualization aspects of cognitive impairment in subcortical arteriosclerotic encephalopathy: med. sci. diss.]. Moscow, 2007. (In Russ.)
  16. Maksimova M.Yu. [Small deep (lacunar) cerebral infarcts in arterial hypertension and atherosclerosis: med. sci. diss.]. Moscow, 2002. (In Russ.)
  17. Levin O.S. [Clinical-magnetic resonance tomography study of study of dyscirculatory encephalopathy with cognitive impairment: med. sci. diss.]. Moscow, 1996. (In Russ.)
  18. Varakin Yu.Ya., Gnedovskaya E.V., Andreeva O.S. et al. [Clinical and pathogenetic aspects of the crisis course of arterial hypertension in patients with the initial manifestations of chronic cerebrovascular disease]. Annals of clinical and experimental neurology 2014; 8(2): 16–21. (In Russ.)
  19. Yakhno N.N. [Dyscirculatory encephalopathy: guidelines]. Moscow: RKI Sovero press, 2005. (In Russ.)
  20. Yakhno N.N., Levin O.S., Damulin I.V. [Comparison of clinical and MRI data with discirculatory encephalopathy. Message 2: cognitive impairment]. Nevrologicheskiy zhurnal 2001; 6(3): 10–19. (In Russ.)
  21. Starchina Yu.A., Parfenov V.A., Chazova I.E. et al. [Cognitive impairment in patients with arterial hypertension]. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova 2008; 108 (4): 19–23. (In Russ.)
  22. Fischer C.M. Lacunes: small, deep cerebral infarcts. Neurology 1965; 15: 774–784. doi: 10.1212/WNL.15.8.774. PMID: 14315302.
  23. Fisher C.M. The arterial lesions underlying lacunes. Acta Neuropathol 1969; 12: 1–15. doi: 10.1007/BF00685305. PMID: 5708546.
  24. Kaiser D., Weise G., Möller K. et al. Spontaneous white matter damage, cognitive decline and neuroinflammation in middle-aged hypertensive rats: an animal model of early-stage cerebral small vessel disease. Acta Neuropathol Commun 2014; 2: 169–183. doi: 10.1186/s40478-014-0169-8. PMID: 25519173.
  25. Dufouil C., de Kersaint-Gilly A., Besançon V. et al. Longitudinal study of blood pressure and white matter hyperintensities the EVA MRI cohort. Neurology 2001; 56: 921–926. doi: 10.1212/WNL.56.7.921. PMID: 11294930.
  26. Marsh E.B., Gottesman R.F., Hillis A.E. et al. Predicting symptomatic intracerebral hemorrhage versus lacunar disease in patients with longstanding hypertension. Stroke 2014; 46: 1679–1683. doi: 10.1161/STROKEAHA.114.005331. PMID: 24811338.
  27. Geraskina L.A., Mashin V.V., Fonyakin A.V. [Features of the circadian rhythm of blood pressure in patients with hypertensive encephalopathy and chronic heart failure]. Arterial'naya gipertenziya 2006; 12(3): 227–231. (In Russ.)
  28. Henskens L.H., Kroon A.A., van Oostenbrugge R.J. et al. Associations of ambulatory blood pressure levels with white matter hyperintensity volumes in hypertensive patients. J Hypertens 2009; 27: 1446–1452. doi: 10.1097/HJH.0b013e32832b5204. PMID: 19502993.
  29. Filomena J., Riba-Llena I., Vinyoles E. et al. Short-term blood pressure variability relates to the presence of subclinical brain small vessel disease in primary hypertension. Hypertension 2015; 66: 634–640. doi: 10.1161/HYPERTENSIONAHA.115.05440. PMID: 26101344.
  30. Rothwell P.M., Howard S.C., Dolan E. et al. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure and episodic hypertension. Lancet 2010; 375: 895–905. doi: 10.1016/S0140-6736 (10)60308 X. PMID: 20226988.
  31. Wardlaw J.M. Blood-brain barrier and cerebral small vessel disease. J Neurol Sci 2010; 299: 66–71. doi: 10.1016/j.jns.2010.08.042. PMID: 20850797.
  32. Wardlaw J.M., Makin S.J., Valdés Hernández M.C. et al. Blood-brain barrier failure as a core mechanism in cerebral small vessel disease and dementia: evidence from a cohort study. Alzheimers Dement 2017; 13: 634–643. doi: 10.1016/j.jalz.2016.09.006.
  33. Hainsworth A.H., Fisher M.J. A dysfunctional blood-brain barrier and cerebral small vessel disease. Neurology 2017; 88: 420–421. doi: 10.1212/WNL.0000000000003561. PMID: 28031393.
  34. Maniega S.M., Chappell F.M., Valdés Hernández M.C. et al. Integrity of normal-appearing white matter: influence of age, visible lesion burden and hypertension in patients with small-vessel disease. J Cereb Blood Flow Metab 2017; 37: 644–656. doi: 10.1177/0271678X16635657. PMID: 26933133.
  35. Geraskina L.A., Fonyakin A.V. [Endothelial function and elastic properties of the vascular wall in hypertensive cerebrovascular diseases]. Annals of clinical and experimental neurology 2009; 3(2): 4–8. (In Russ.)
  36. Mchedlishvili G.I. [The function of the vascular mechanisms of the brain: their role in the regulation and in the pathology of cerebral circulation]. Moscow: Nauka, 1968. (In Russ.)
  37. Tarumi T., Thomas B.P., Wang C. et al. Ambulatory pulse pressure, brain neuronal fiber integrity, and cerebral blood flow in older adults. J Cereb Blood Flow Metab 2017: 0271678X17745027. doi: 10.1177/0271678X17745027. PMID: 29219028.
  38. Fazekas F., Chawluk J.B., Alavi A. et al. MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. Am J Roentgen 1987; 149: 351–356. doi: 10.2214/ajr.149.2.351. PMID: 3496763.
  39. Albert M.S., DeKosky S.T., Dickson D. et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011; 7: 270–279. doi: 10.1016/j.jalz.2011.03.008. PMID: 21514249.
  40. McKhann G.M., Knopman D.S., Chertkow H. et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7: 263–269. doi: 10.1016/j.jalz.2011.03.005. PMID: 21514250.
  41. Mancia G., Fagard R., Narkiewicz K. 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). Blood Pressure 2013; 22: 193–278. doi: 10.3109/08037051.2013.812549. PMID: 23777479.
  42. Rogoza A.N., Nikol'skiy V.P., Oshchepkova E.V. et al. [24-hour ambulatory blood pressure monitoring in hypertension (Methodological issues)]. Moscow, 1997. 44 p. (In Russ.)
  43. Ratova L.G., Dmitriev V.V., Tolpygina S.N., Chazova I.E. [Daily blood pressure monitoring in clinical practice]. Consilium medicum 2001; 3(13): 56–59. (In Russ.).
  44. O’Brien E., Parati G., Stergiou G. et al. European Society of Hypertension position paper on ambulatory blood pressure monitoring. J Hypertens 2013; 31: 1731–1768. doi: 10.1097/HJH.0b013e328363e964. PMID: 24029863.
  45. Leemans A., Jones D.K. The B-matrix must be rotated when correcting for subject motion in DTI data. Magn Reson Med 2009; 61: 1336–1349. doi: 10.1002/mrm.21890. PMID: 19319973.
  46. Kim K.W., MacFall J.R., Payne M.E. Classification of white matter lesions on magnetic resonance imaging in elderly persons. Biol Psychiatry 2008; 64: 273–280. doi: 10.1016/j.biopsych.2008.03.024. PMID: 18471801.
  47. Dufouil C., Chalmers J., Coskun O. et al. Effects of blood pressure lowering on cerebral white matter hyperintensities in patients with stroke: the PROGRESS (Perindopril Protection Against Recurrent Stroke Study) Magnetic Resonance Imaging Substudy. Circulation 2005; 112: 1644–1650. doi: 10.1161/CIRCULATIONAHA.104.501163. PMID: 16145004
  48. Weber R., Weimar C., Blatchford J. et al. Telmisartan on top of antihypertensive treatment does not prevent progression of cerebral white matter lesions in the prevention regimen for effectively avoiding second strokes (PRoFESS) MRI substudy. Stroke 2012; 43: 2336–2342. doi: 10.1161/STROKEAHA.111.648576. PMID: 22738922.
  49. Sachdev P., Wen W., Chen X., Brodaty H. Progression of white matter hyperintensities in elderly individuals over 3 years. Neurology 2007; 68: 214–222. doi: 10.1212/01.wnl.0000251302.55202.73. PMID: 17224576.
  50. Schmidt R., Schmidt H., Haybaeck J. et al. Heterogeneity in age-related white matter changes. Acta Neuropathol 2011; 122: 171–185. doi: 10.1007/s00401-011-0851-x. PMID: 21706175.
  51. Pasi M., van Uden I.W., Tuladhar A.M. et al. White matter microstructural damage on diffusion tensor imaging in cerebral small vessel disease: clinical consequences. Stroke 2016; 47: 1679–1684. doi: 10.1161/STROKEAHA.115.012065. PMID: 27103015.
  52. Song S.K., Yoshino J., Le T.Q. et al. Demyelination increases radial diffusivity in corpus callosum of mouse brain. Neuroimage 2005; 26: 132–140. doi: 10.1016/j.neuroimage.2005.01.028. PMID: 15862213.
  53. Sun S.W., Liang H.F., Le T.Q. et al. Differential sensitivity of in vivo and ex vivo diffusion tensor imaging to evolving optic nerve injury in mice with retinal ischemia. Neuroimage 2006; 32: 1195–1204. doi: 10.1016/j.neuroimage.2006.04.212. PMID: 16797189
  54. Papma J.M., de Groot M., de Koning I. et al. Cerebral small vessel disease affects white matter microstructure in mild cognitive impairment. Human Brain Mapping 2014; 35: 2836–2851. doi: 10.1002/hbm.22370. PMID: 24115179.
  55. Dobrynina L.A., Gnedovskaya E.V., Sergeeva A.N. et al. [MRI changes in the brain for asymptomatic first-time diagnosed arterial hypertension]. Annals of clinical and experimental neurology 2016; 10(3); 25–32. (In Russ.)
  56. Dobrynina L.A., Gnedovskaya E.V., Sergeyeva A.N. et al. [Subclinical cerebral manifestations and brain damage for asymptomatic first-time diagnosed arterial hypertension]. Annals of clinical and experimental neurology 2016; 10(3); 33–39. (In Russ.)
  57. Gons R.A., de Laat K.F., van Norden A.G. et al. Hypertension and cerebral diffusion tensor imaging in small vessel disease. Stroke 2010; 41: 2801–2806. doi: 10.1161/STROKEAHA.110.597237. PMID: 21030696.
  58. Parfenov V.A., Ostroumova T.M., Ostroumova O.D. et al. [Diffusion tensor magnetic resonance imaging in the diagnosis of white matter lesion in middle-aged patients with uncomplicated essential hypertension]. Nevrologiya, nejropsihiatriya, psihosomatika 2018; 10(2): 20–26. doi: 10.14412/2074-2711-2018-2-20-26. (In Russ.)
  59. Schwartz G.L., Bailey K.R., Mosley T. et al. Association of ambulatory blood pressure with ischemic brain injury. Hypertension 2007; 49: 1228–1234. doi: 10.1161/HYPERTENSIONAHA.106.078691. PMID: 17404188.
  60. Siennicki-Lantz A., Reinprecht F., Axelsson J., Elmståhl S. Cerebral perfusion in the elderly with nocturnal blood pressure fall. Eur J Neurol 2007; 14: 715–720. doi: 10.1111/j.1468-1331.2007.01805.x. PMID: 17594325.
  61. Bubb E.J., Metzler-Baddeley C., Aggleton J.P. The cingulum bundle: anatomy, function, and dysfunction. Neurosci Biobehav Rev 2018; 92: 104–127. doi: 10.1016/j.neubiorev.2018.05.008. PMID: 29753752.
  62. Van der Holst H.M., Tuladhar A.M., van Norden A.G. et al. Microstructural integrity of the cingulum is related to verbal memory performance in elderly with cerebral small vessel disease: the RUN DMC study. Neuroimage 2013; 65: 416–423. doi: 10.1016/j.neuroimage.2012.09.060. PMID: 23032491.
  63. De Simone G., Pasanisi F. Systolic, diastolic and pulse pressure: pathophysiology. Ital Heart J 2001; 2: 359–362. PMID: 19397007.
  64. Midha T., Lalchandani A., Nath B. et al. Prevalence of isolated diastolic hypertension and associated risk factors among adults in Kanpur, India. Ind Heart J 2012; 64: 374–379. doi: 10.1016/j.ihj.2012.06.007. PMID: 22929820.
  65. Franklin S.S., Pio J.R., Wong N.D. et al. Predictors of new-onset diastolic and systolic hypertension: the Framingham Heart Study. Circulation 2005; 111: 1121–1127. doi: 10.1161/01.CIR.0000157159.39889.EC. PMID: 15723980.
  66. Hozawa A., Ohkubo T., Nagai K. et al. Prognosis of isolated systolic and isolated diastolic hypertension as assessed by self-measurement of blood pressure at home: the Ohasama study. Arch Int Med 2000; 160: 3301–3306. doi: 10.1001/archinte.160.21.3301. PMID: 11088093.
  67. Caso V., Agnelli G., Alberti A. et al. High diastolic blood pressure is a risk factor for in-hospital mortality in complete MCA stroke patients. Neurol Sci 2012; 33: 545–549. doi: 10.1007/s10072-011-0767-1. PMID: 21948055.

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Copyright (c) 2019 Dobrynina L.A., Shamtieva K.V., Кремнева Е.И., Kalashnikova L.A., Krotenkova M.V., Gnedovskaya E.V., Berdalin A.B.

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