Published Online
on August 1, 2005

A more recent version of this article appeared on August 9, 2005

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Submitted on September 11, 2004
Revised on March 17, 2005
Accepted on April 12, 2005

C-Reactive Protein and Cerebral Small-Vessel Disease. The Rotterdam Scan Study

E. J. van Dijk MD, PhD, N. D. Prins MD, PhD, S. E. Vermeer MD, PhD, H. A. Vrooman PhD, A. Hofman MD, PhD, P. J. Koudstaal MD, PhD, and M. M.B. Breteler MD, PhD^*

From the Department of Epidemiology & Biostatistics (E.J.v.D., N.D.P., S.E.V., A.H., M.M.B.B.), Department of Neurology (E.J.v.D., N.D.P., S.E.V., P.J.K.), and Department of Medical Informatics and Department of Radiology (H.A.V.), Erasmus Medical Center, Rotterdam, the Netherlands.

^* To whom correspondence should be addressed. E-mail: m.breteler{at}erasmusmc.nl.

Background--Inflammatory processes are involved in the development and consequences of atherosclerosis. Whether these processes are also involved in cerebral small-vessel disease is unknown. Cerebral white matter lesions and lacunar brain infarcts are caused by small-vessel disease and are commonly observed on MRI scans in elderly people. These lesions are associated with an increased risk of stroke and dementia. We assessed whether higher C-reactive protein (CRP) levels were related to white matter lesion and lacunar infarcts.

Methods and Results--We based our study on 1033 participants of the population-based Rotterdam Scan Study for whom complete data on CRP levels were available and who underwent brain MRI scanning. Subjects were 60 to 90 years of age and free of dementia at baseline. Six hundred thirty-six subjects had a second MRI scan on average 3.3 years later. We used multivariate regression models to assess the associations between CRP levels and markers of small-vessel disease. Higher CRP levels were associated with presence and progression of white matter lesions, particularly with marked lesion progression (ORs for highest versus lowest quartile of CRP 3.1 [95% CI 1.3 to 7.2] and 2.5 [95% CI 1.1 to 5.6] for periventricular and subcortical white matter lesion progression, respectively). These associations persisted after adjustment for cardiovascular risk factors and carotid atherosclerosis. Persons with higher CRP levels tended to have more prevalent and incident lacunar infarcts.

Conclusions--Inflammatory processes may be involved in the pathogenesis of cerebral small-vessel disease, in particular, the development of white matter lesions.

Key words: inflammation • magnetic resonance imaging • cerebral infarction • microcirculation • cerebral ischemia

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C-Reactive Protein and Cerebral Small-Vessel Disease: An Opportunity to Reassess Small-Vessel Disease Physiopathology?

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