Introduction: Arteriosclerosis is characterized by the loss of smooth muscle cells and a hyalinized thickened wall, and concentric narrowing of the lumen in penetrating arteries causes cerebral small vessel disease, including lacunar infarcts, deep white matter lesions, and cerebral microbleeds mainly in the basal ganglia. Although infrequently fatal, lacunar infarcts and deep white matter lesions, which account for 30% of ischemic strokes in Japan, are associated with a high risk of recurrence and cognitive impairment. Basic studies have reported on the importance of inflammation in the pathogenesis of arteriosclerosis.
Hypothesis: We investigated the hypothesis that serum high sensitive C-reactive protein (hs-CRP) levels have some effect on cerebral small vessel (CSV)-related lesions.
Methods: From January 2008 to March 2013, a total of 1,362 Japanese subjects voluntarily participated in the health checkup system. We selected 519 neurologically normal subjects (284 males and 235 females) aged 29-90 years (mean, 63.5 ± 10.3 years) from these participants for inclusion. All the participants underwent MRI, and their CSV-related lesions (i.e., lacunar infarcts, cerebral microbleeds, deep white matter hyperintensity, and periventricular hyperintensity) were evaluated. The serum levels of hs-CRP were evaluated as common inflammatory markers.
Results: Subjects with higher hs-CRP levels had more lacunar infarcts (p = 0.02). After adjusting for the traditional cardiovascular risk factors, higher hs-CRP levels were still associated with the presence of lacunar infarcts (odds ratio for the highest vs. the lowest tertile of hs-CRP, 3.57 [95% confidence interval: 1.30-9.80]). These associations did not change when the logarithmically transformed values for hs-CRP were included. Furthermore, subjects with higher CRP levels had more cerebral microbleeds (p = 0.03), more severe deep white matter hyperintensity (p = 0.04), and periventricular hyperintensity (p = 0.04); however, these associations were not observed after adjusting for the cardiovascular risk factors.
Conclusions: Higher levels of hs-CRP were associated with lacunar infarcts. Thus, inflammatory processes may be involved in the pathogenesis of small vessel disease.