Cerebral White Matter Lesions and Microbleeds: Tiny but Meaningful Indicators of Hypertensive Damage

5 Hypertens Res Vol.31 (2008) No.1 p.5-6 Editorial Comment Cerebral White Matter Lesions and Microbleeds: Tiny but Meaningful Indicators of Hypertensive Damage Kazunori TOYODA1) (Hypertens Res 2008; 31: 5–6) Key Words: magnetic resonance imaging, leukoaraiosis, cerebral microbleeds, stroke, hypertension The development of MRI has enabled small subclinical cerebral abnormalities to be detected. Among these various abnormalities, patchy or confluent cerebral white matter lesions (WMLs), referred to as leukoaraiosis (from the Greek leuko = white and araiosis = rarefied) (1), are seen as hyperintensities on T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences. WMLs are common in the general elderly population (2), as Ohmine et al. (3) report in this issue of Hypertension Research. Stenosis or occlusion of small cerebral vessels with sudden or chronic ischemia can lead to incomplete white matter infarction and is considered to play a central role in the pathogenesis of WMLs (4). Alternative mechanisms include alterations of blood-brain barrier permeability either during chronic hypertension or in relation to impaired venous return within the deep white matter (5). Major trials have reported that the presence of WMLs is an independent predictor of stroke (6–8). Although several studies including a recent multicenter, multinational Leukoaraiosis and Disability (LADIS) study (9) showed a strong association between WMLs and general cognitive dysfunction, the contribution of WMLs to vascular dementia is still controversial (4). In addition to age, hypertension is one of the most important risk factors for WMLs (10). Increased office blood pressure (BP) levels (11–13), as well as ambulatory BP levels (14–16), are associated with severe WMLs. Successful antihypertensive treatment ameliorates (11–13) and a nondipping circadian pattern enhances the severity of WMLs (16). WMLs are associated with both large-artery atherosclerosis and small-artery endothelial dysfunction (10). In addition, WMLs have been found to be related to new clinical entities, including the metabolic syndrome (17) and chronic kidney disease (18). Thus, WMLs are good predictors of subtle, as well as advanced, systemic vascular organ damage. The study by Ohmine et al. (3) is unique in that it sought to identify a “predictor” of this “MRI-detectable predictor.” The results revealed that an increase in arterial stiffness, which is easily and non-invasively evaluated by the brachial-ankle pulse wave velocity (ba-PWV), is associated with the presence of WMLs. Furthermore, the authors categorized WMLs into two distinct types, periventricular hyperintensities (PVH) and deep WMLs; after adjustment for traditional risk factors, they found that elevated ba-PWV was independently related to PVH, but not deep WMLs. The authors suggest that this difference between the two types may be explained by the fact that, in the early phase of atherosclerosis, ba-PWV mainly reflects functional change (sclerosis) rather than morphological change (atherosis) of the vascular wall, and the functional damage can affect PVH more than deep WMLs. However, one cannot yet conclusively state that the two types of WMLs have a different association with ba-PWV, mainly because the study of Ohmine et al. (3) had such a small number of patients, particularly patients having advanced WMLs. I anticipate that the authors will do further studies to determine the detailed contribution of ba-PWV to the two types of WMLs, since their studies based on brain MRIs of an elderly population in a rural community (Sefuri, Japan) have already identified several clinical characteristics of WMLs and silent From the 1)Cerbrovascular Division, Department of Medicine, National Cardiovascular Center, Suita, Japan. Address for Reprints: Kazunori Toyoda, M.D., Cerebrovascular Division, Department of Medicine, National Cardiovascular Center, 5–7–1 Fujishirodai, Suita 565–8565, Japan. E-mail: Received October 12, 2007. 6 Hypertens Res Vol. 31, No. 1 (2008) brain infarction (19–22). Cerebral microbleeds may be another important indicator of arteriosclerosis; they are tiny, subclinical lesions that are detectable only by gradient-echo T2*-weighted MRI (23, 24). Although the clinical significance of cerebral microbleeds has not been established, several studies suggest that they are associated with hypertension and vascular organ damage. An interesting study on microbleeds has been previously published in this journal (25). Both WMLs and microbleeds are related to small-artery cerebrovascular lesions, which are common in the Asian population. Many issues related to these tiny cerebral abnormalities will need to be elucidated by hypertension researchers. References 1. Hachinski VC, Potter P, Merskey H: Leuko-araiosis. Arch Neurol 1987; 44: 21–23. 2. van Dijk EJ, Prins ND, Vermeer SE, Koudstaal PJ, Breteler MM: Frequency of white matter lesions and silent lacunar infarcts. J Neural Transm Suppl 2002; 25: 25–39. 3. Ohmine T, Miwa Y, Yao H, et al: Association between arterial stiffness and cerebral white matter lesions in community-dwelling elderly subjects. Hypertens Res 2008; 31: 75– 81. 4. Schmidt R, Petrovic K, Ropele S, Enzinger C, Fazekas F: Progression of leukoaraiosis and cognition. Stroke 2007; 38: 2619–2625. 5. Munoz DG: Leukoaraiosis and ischemia: beyond the myth. Stroke 2006; 37: 1348–1349. 6. Wong TY, Klein R, Sharrett AR, et al: Cerebral white matter lesions, retinopathy, and incident clinical stroke. JAMA 2002; 288: 67–74. 7. Vermeer SE, Hollander M, van Dijk EJ, et al: Silent brain infarcts and white matter lesions increase stroke risk in the general population: the Rotterdam Scan Study. Stroke 2003; 34: 1126–1129. 8. Kuller LH, Longstreth WT Jr, Arnold AM, et al: White matter hyperintensity on cranial magnetic resonance imaging: a predictor of stroke. Stroke 2004; 35: 1821–1825. 9. van der Flier WM, van Straaten EC, Barkhof F, et al: Small vessel disease and general cognitive function in nondisabled elderly: the LADIS study. Stroke 2005; 36: 2116–2120. 10. Ovbiagele B, Saver JL: Cerebral white matter hyperintensities on MRI: current concepts and therapeutic implications. Cerebrovasc Dis 2006; 22: 83–90. 11. 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: 2262–2270. 12. de Leeuw FE, de Groot JC, Oudkerk M, et al: Hypertension and cerebral white matter lesions in a prospective cohort study. Brain 2002; 125: 765–772. 13. van Dijk EJ, Breteler MM, Schmidt R, et al: The association between blood pressure, hypertension, and cerebral white matter lesions: cardiovascular determinants of dementia study. Hypertension 2004; 44: 625–630. 14. Goldstein IB, Bartzokis G, Guthrie D, Shapiro D: Ambulatory blood pressure and the brain: a 5-year follow-up. Neurology 2005; 64: 1846–1852. 15. va (...truncated)