Published Online
on September 6, 2005

A more recent version of this article appeared on September 13, 2005

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Submitted on August 18, 2004
Revised on March 21, 2005
Accepted on May 25, 2005

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

Carole Dufouil PhD, John Chalmers MD, PhD, Oguzhan Coskun MD, Véronique Besançon MD, Marie-Germaine Bousser MD, Pierre Guillon PhD, Stephen MacMahon PhD, Bernard Mazoyer MD, PhD, Bruce Neal MD, PhD, Mark Woodward PhD, Nathalie Tzourio-Mazoyer MD, PhD, Christophe Tzourio MD, PhD^*, for the PROGRESS MRI Substudy Investigators

From the INSERM U708, Paris, France (C.D., V.B., C.T.); The George Institute for International Health, Sydney, Australia (J.C., S.M., B.N., M.W., C.T.); the UMR6194 CNRS-CEA, and Unite IRM, CHU de Caen, France (O.C., P.G., B.M., N.T.-M.); and the Service de Neurologie, Hôpital Lariboisière, Paris, France (M.-G.B., C.T.).

^* To whom correspondence should be addressed. E-mail: tzourio{at}chups.jussieu.fr.

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 (SD=6.0 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. The risk of new WMH was reduced by 43% (95% CI -7% to 89%) in the active treatment group compared with the placebo group (P=0.17). The mean total volume of new WMHs was significantly reduced in the active treatment group (0.4 mm³ [SE=0.8]) compared with the placebo group (2.0 mm³ [SE=0.7]; P=0.012). This difference was greatest for patients with severe WMH at entry, 0.0 mm³ (SE=0) in the active treatment group versus 7.6 mm³ (SE=1.0) in the placebo group (P<0.0001).

Conclusions--These results indicate that an active blood pressure-lowering regimen stopped or delayed the progression of WMHs in patients with cerebrovascular disease.

Key words: stroke • cerebrovascular disorders • magnetic resonance imaging • hypertension • trials

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