Hypertension is a major risk factor for severe WMH. Subjects taking antihypertensive drugs and who have controlled blood pressure had a reduced risk of severe WMH. Longitudinal studies are needed to investigate whether reduction of the development of WMH, by treatment and prevention of hypertension, might reduce the subsequent risk of cognitive deterioration or stroke.

Background-The prevalence of white matter hyperintensities (WMHs) detected on cerebral MRI is associated with hypertension, but it is not known whether blood pressure lowering can arrest their progression. We report here the results of an MRI substudy of PROGRESS (Perindopril Protection Against Recurrent Stroke Study), a randomized trial of blood pressure lowering in subjects with cerebrovascular disease. Methods and Results-The substudy comprised 192 participants who had a cerebral MRI both at baseline and after a mean follow-up time of 36 months (SDϭ6.0 months). At the first MRI, WMHs were graded with a visual rating scale from A (no WMH) to D (severe WMH). Participants were assigned to a combination of perindopril plus indapamide (or their placebos; 58%) or to single therapy with perindopril (or placebo). At the time of the second MRI, the blood pressure reduction in the active arm compared with the placebo arm was 11.2 mm Hg for systolic blood pressure and 4.3 mm Hg for diastolic blood pressure. Twenty-four subjects (12.5%) developed new WMHs at follow-up.

Background and Purpose: White matter hyperintensities (WMHs) are often observed on cerebral magnetic resonance imaging (MRI) of elderly individuals. Epidemiological studies have shown that age and hypertension are associated with WMHs, suggesting a vascular mechanism in WMH pathogenesis. In a population-based prospective study, we examined the association of carotid atherosclerosis measured at baseline and 4-year follow-up with severity of WMHs assessed at 4-year follow-up. Methods: The sample consisted of 640 healthy subjects aged 59–71 years at entry enrolled in the prospective EVA Study. Systolic and diastolic blood pressures were measured at each wave. Ultrasonographic measures of intima-media thickness (IMT) of the common carotid arteries and plaques were made at baseline and at 4-year follow-up examination. An MRI examination was performed at 4-year follow-up. The presence and severity of WMHs were evaluated by a single radiologist. Results: After adjusting for age, gender, and hypertension, the presence of carotid plaques at baseline was significantly associated with the presence of severe WMHs 4 years later [odds ratio (OR) = 1.70; 95% confidence interval (CI): 1.05–2.74]. The association was stronger in men than in women. A 0.1-mm increase of baseline IMT was associated with an increased risk of severe WMHs in both sexes (adjusted OR = 1.17; 95% CI: 0.96–1.41), but the association was not significant (p = 0.12). Cross-sectional relationships between carotid plaques and severe WMHs at 4-year follow-up showed that the risk of having severe WMHs was stronger in the group of subjects who had already plaques at study entry compared to the group of subjects whose plaques occurred during 4-year follow-up. Conclusion: This study confirmed an association between carotid atherosclerosis and WMHs independently of age and hypertension. It also suggested that the older the carotid plaques, the higher the risk of having severe WMHs.

The association between aldosterone synthase (CYP11B2) gene polymorphism and white matter hyperintensities seen on cerebral MRI was studied in a population-based sample of 829 individuals aged 63 to 75 years. The T allele was associated with the risk of severe white matter hyperintensities. Compared with the CC genotype, the adjusted OR for severe white matter hyperintensities was 4.61 (95% CI, 1.46 to 14.55) for the TT genotype and 2.45 (95% CI, 0.81 to 7.46) for the TC genotype in men. This association was independent of hypertension.

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