Published Online
on March 3, 2005

A more recent version of this article appeared on April 1, 2005

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Submitted on August 12, 2004
Revised on December 13, 2004
Accepted on January 11, 2005

Relations of Serum High-Sensitivity C-Reactive Protein and Interleukin-6 Levels With Silent Brain Infarction

Taku Hoshi MD^*; Kazuo Kitagawa MD, PhD; Hiroshi Yamagami MD, PhD; Shigetaka Furukado MD; Hidetaka Hougaku MD, PhD; and Masatsugu Hori MD, PhD

From the Division of Stroke Medicine, Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, Osaka, Japan.

^* To whom correspondence should be addressed. E-mail: thoshi{at}medone.med.osaka-u.ac.jp.

Background and Purpose--Small silent brain infarction (SBI) is often found on magnetic resonance (MR) images of apparently healthy individuals at cardiovascular risk. Particularly, small SBI found in subcortical white matter, basal ganglia, or thalamus is thought to be caused by cerebral small vessel disease. Although several lines of evidence suggest a role of inflammatory processes in atherothrombotic vascular events, their involvement in SBI remains to be determined. This study examines the associations between serum inflammatory markers and SBI as a manifestation of cerebral small vessel disease.

Methods--One hundred ninety-four patients without histories of cardiovascular accidents were prospectively enrolled for this study. All patients underwent brain MR imaging and carotid ultrasonography, and patients with SBI diagnosed underwent further MR angiography. As common inflammatory markers, serum levels of high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) were evaluated.

Results--SBIs were found in 40 patients, and all of those were located in subcortical and infratentorial area, without MR angiographic evidence for obstructive lesions in proximal cerebral arteries. Mean hsCRP and IL-6 levels were higher in patients with SBI than in those without. Also, higher levels of both hsCRP (odds ratio [OR], 1.85 per standard deviation [SD] increase) and IL-6 (OR, 2.00/SD increase) were associated with higher likelihood for SBI. Moreover, the associations were only slightly attenuated when adjusting traditional cardiovascular risk factors and carotid IMT.

Conclusions--Higher levels of hsCRP and IL-6 appear to be associated with small SBI, suggesting a role of inflammatory processes in cerebral small vessel disease.

Key words: inflammation • interleukins • magnetic resonance imaging

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