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Blood Pressure and White Matter Hyperintensity Volume – A Review of the Relationship and Implications for Stroke Prediction and Prevention

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Published Online: Jun 27th 2012 European Neurological Review, 2012;7(3):174–7 DOI:
Authors: Royya Modir, Hannah Gardener, Clinton B Wright
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A heavy burden of white matter hyperintensities (WMH) is a risk factor for stroke and vascular cognitive impairment making it important to understand their pathophysiology, aetiology and clinical implications. Ageing studies suggest a linear relationship between blood pressure (BP) and both WMH and microstructural integrity in normal-appearing white matter and, after age, hypertension is the strongest risk factor for WMH. Numerous large population-based observational studies have reported significant associations between elevated BP and WMH burden, however, the relative importance of systolic versus diastolic BP remains controversial. Limitations of prior studies include the use of only a single measurement of BP and oversimplifying hypertension as a dichotomous variable. Race/ethnic differences in the association between BP and WMH have been suggested, but most studies only included older Caucasians. Antihypertensive treatment has been demonstrated to slow WMH progression, but lowering BP in the elderly may also reduce brain perfusion in those with poor autoregulation. Ongoing trials aim to clarify the effects of BP treatment on WMH progression in multi-ethnic populations and the implications of these findings for stroke prevention require further study.


Leukoaraiosis, vascular cognitive impairment, blood pressure, hypertension, cerebral small vessel disease, white matter hyperintensities


With the ever-increasing availability and clinical use of brain magnetic resonance imaging (MRI), the frequency of white matter hyperintensities (WMH) has become more readily apparent. As a heavy burden of WMH has been shown to be an important risk factor for incident stroke as well as vascular cognitive impairment,1 it is important to understand the pathophysiology, aetiology and clinical implications of WMH volume. Evidence suggests that hypertension is the strongest modifiable risk factor for WMH2–8 and raises the possibility of both prevention and treatment strategies, but clinical trials are lacking and further studies are needed.

WMH are demonstrated on T2-weighted MRI sequences. These damaged regions are evidenced on the T2 sequence as high signal intensity, which appear bright.9 They are considered white matter lesions if hyperintense on T2-weighted, fluid-attenuated inversion recovery and proton density images, without prominent hypointensity on T1-weighted images.1 They indicate areas of increased brain water content in white matter tissue, but the degree of damage to axons and supporting cells is not clear and remains an area under study (see Pathology section below).9 Recent evidence using diffusion tensor imaging has suggested a linear relationship between blood pressure levels and the microstructural integrity of both normal-appearing white matter and white matter hyperintensities. In hypertensive patients, the microstructural integrity of the cerebral white matter is significantly more affected than in normotensive patients.10

Pathology of White Matter Hyperintensities
The most common areas affected by WMH are in the deep white matter of the cerebral hemispheres, especially in the distribution of end-arteries and arterioles that supply a border-zone territory with minimal irrigation by collateral vessels. In areas identified as hyperintensities on MRI, pathological studies have reported myelin pallor, loss of tissue density, myelin and axonal loss, and gliosis.11,12 These lesions are hypothesised to be caused by chronic hypoperfusion of the white matter due to low-grade vascular insufficiency resulting in ischaemia,12 and are often associated with structural changes of the vessels, including hyalinisation, tortuosity, elongation and narrowing with arteriosclerosis and lipohyalinosis.12,13 Many of these changes have been associated with hypertension.14

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Article Information:

The authors have no conflicts of interest to declare.


Clinton B Wright, Department of Neurology, Evelyn F McKnight Brain Institute, Leonard M Miller School of Medicine, University of Miami, CRB 1349, 1120 NW 14th Street, Miami, FL 33136, US. E:




  1. Debette S, Markus HS, The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis, BMJ, 2010;341:c3666
  2. Breteler MMB, van Swieten JC, Bots ML, et al., Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: the Rotterdam Study, Neurology, 1994;44:1246–52.
  3. Longstreth WT Jr, Manolio TA, Arnold A, et al., Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. The Cardiovascular Health Study, Stroke, 1996;27:1274–82.
  4. Liao D, Cooper L, Cai J, et al., The prevalence and severity of white matter lesions, their relationship with age, ethnicity, gender, and cardiovascular disease risk factors: the ARIC Study, Neuroepidemiology, 1997;16:149–62.
  5. 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;27:2262–70.
  6. de Leeuw FE, de Groot JC, Oudkerk M, et al., A follow-up study of blood pressure and cerebral white matter lesions, Ann Neurol, 1999;46:827–33.
  7. Jeerakathil T, Wolf PA, Beiser A, et al., Stroke risk profile predicts white matter hyperintensity volume: the Framingham Study, Stroke, 2004;35:1857–61.
  8. 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;112:1644–50.
  9. Ovbiagele B, Saver JL, Cerebral white matter hyperintensities on MRI: current concepts and therapeutic implications, Cerebrovascular Diseases, 2006;22(2–3):83–90.
  10. Gons RA, de Laat KF, van Norden AG, et al., Hypertension and cerebral diffusion tensor imaging in small vessel disease, Stroke, 2010;41:2801–6.
  11. Fazeka F, Kleinert R, Offenbacher H, et al., Pathologic correlates of incidental MRI white matter signal hyperintensities, Neurology, 1993;43:1683–9.
  12. Pantoni L, Garcia JH, Pathogeneisis of leukokaraiosis: a review, Stroke, 1997;28:652–9.
  13. Moody D, Sanamore WP, Bell MA, Does Tortuosity in cerebral arterioles impair down-autoregulation in hypertensives and elderly normotensives? A hypothesis and computer model, Clin Neurosurg, 1991;37:372–87.
  14. Ostrow PT, Miller LL, Pathology of small artery disease, Adv Neurol, 1993;62:93–123.
  15. Wardlaw JM, Sandercock PAG, Dennis MS, Starr J, Is breakdown of the blood-brain barrier responsible for lacunar stroke, leukoaraiosis, and dementia?, Stroke, 2003;34:806–11.
  16. Pantoni L, Garcia JH, The significance of cerebral white matter abnormalities 100 years after Binswanger's report. A review, Stroke, 1995;26:1293–301.
  17. Wright CB, Moon Y, Paik MC, et al., Inflammatory biomarkers of vascular risk as correlates of leukoariosis, Stroke, 2009;40:3466–71.
  18. Moody DM, Brown WR, Challa VR, Anderson RL, Periventricular venous collagenosis: association with leukoaraiosis, Radiology, 1995;194:469–76.
  19. Ylikoski A, Erkinjuntti T, Raininko R, et al., White matter hyperintensities on MRI in the neurologically nondiseased elderly. Analysis of cohorts of consecutive subjects aged 55 to 85 years living at home, Stroke, 1995;26:1171–7.
  20. Garde E, Mortensen EL, Krabbe K, et al., Relation between age-related decline in intelligence and cerebral white-matter hyperintensities in healthy octogenarians: a longitudinal study, Lancet, 2000;356:628–34.
  21. Bots ML, van Swieten JC, Breteler MMB, et al., Cerebral white matter lesions and atherosclerosis in the Rotterdam Study, Lancet, 1993;341:1232–7.
  22. Lindgren A, Roijer A, Rudling O, et al., Cerebral lesions on magnetic resonance imaging, heart disease, and vascular risk factors in subjects without stroke: a population-based study, Stroke, 1994;25:929–34.
  23. Hajjar I, Kotchen TA, Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988–2000, JAMA, 2003;290:199–206.
  24. Dufouil C, de Kersaint-Gilly A, Besancon V, et al., Longitudinal study of blood pressure and white matter hyperintensities: the EVA MRI Cohort, Neurology, 2001;56:921–6.
  25. de Leeuw FE, de Groot JC, Oudkerk M, et al., Hypertension and white matter lesions in a prospective cohort study, Brain, 2002;125;765–72.
  26. Launer LJ, Masaki K, Petrovitch H, et al., The association between midlife blood pressure levels and late-life cognitive function: The Honolulu-Asia Aging Study, JAMA, 1995;274:1846–51.
  27. Marcus J, Gardener H, Rundek T, et al., Baseline and longitudinal increases in diastolic blood pressure are associated with greater white matter hyperintensity volume: the Northern Manhattan study, Stroke, 2011;42(9):2639–41.
  28. Guo X, Pantoni L, Simoni M, et al., Blood pressure components and changes in relation to white matter lesions: a 32-year prospective population study, Hypertension, 2009;54:57–62.
  29. Pinto E, Blood Pressure and ageing, Postgrad Med J, 2007;83:109–14.
  30. Benetos A, Thomas F, Safar ME, et al., Should diastolic and systolic blood pressure be considered for cardiovascular risk evaluation: a study on middle-aged men and women, J Am Coll Cardiol, 2001;37:163–8.
  31. Godin O, Tzourio C, Maillard P, et al., Antihypertensive treatment and change in blood pressure are associated with the progression of white matter lesion volumes: the three-city (3C)-dijon magnetic resonance imaging study, Circulation, 2011;123:266–73.
  32. Gottesman RF, Coresh J, Catellier DJ, et al., Blood pressure and white-matter disease progression in a biethnic cohort: Atherosclerosis Risk in Communities (ARIC) Study, Stroke, 2010;41:3–8.

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