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.

Objective-Elevated circulating levels of IL-18 can predict future coronary heart disease. Although IL-18 is thought to play a crucial role in atherosclerosis, whether circulating IL-18 levels are associated with the severity of atherosclerosis remains to be determined. With the use of B-mode ultrasound, this study examines the relationships of serum IL-18 levels with carotid intima-media thickness (IMT) as a reflector for systemic atherosclerosis. Methods and Results-The study comprised 366 patients without histories of cardiovascular accidents. Severity of carotid atherosclerosis was evaluated by the mean max IMT, ie, mean of the maximal wall thickness at 12 carotid segments. Serum IL-18, IL-6, and high-sensitive C-reactive protein (hs-CRP) levels were determined in all patients. Logtransformed IL-18 concentrations were positively correlated with IMT (rϭ0.36, PϽ0.001), and the association remained significant (␤ϭ0.20, PϽ0.001) when controlling for traditional atherosclerotic risk factors, IL-6 and hs-CRP levels. Also, IMT was greater in the highest and the middle tertile of IL-18 levels than in the lowest tertile. Conclusion-Higher

Background and Purpose: There is epidemiological evidence that increased carotid intima-media thickness (IMT) is a predictor of cardiovascular disease (CVD) events. However, the significance of carotid IMT in high-risk patients in whom risk factors are managed clinically has not been adequately investigated. The purpose of this study was to determine the usefulness of carotid IMT measurement in such patients. Methods: The study comprised 900 outpatients with cardiovascular risk factors or established atherosclerosis. Carotid IMT was calculated as the mean bilateral IMT of the common carotid artery, bifurcation, and internal carotid artery. Baseline vascular risk factors, medications, and history of CVD were recorded at the time of enrollment. The incidence of CVD events was determined prospectively. Results: During a mean follow-up period of 2.6 years, there were 64 CVD events. The relative risk (RR) of a CVD event increased with increased IMT. Association between CVD events and carotid IMT was significant after adjustment for risk factors and history of CVD, showing an increased risk per IMT tertile from the middle tertile (RR, 2.5; 95% confidence interval [CI]: 1.0–6.3) to the highest (RR, 3.6; 95% CI: 1.4–9.0). When patients with a history of CVD were excluded (n = 574), the predictive value of IMT was significant even after adjustment for risk factors (hazard ratio per 1 SD IMT increase was 1.57 [95% CI: 1.11–2.20]). Conclusions: Carotid IMT is an independent predictor of vascular events in high-risk patients in whom risk factors are managed clinically.

Background and Purpose-Higher plasma total homocysteine (tHcy) levels have been associated with carotid atherosclerosis and cerebral infarction in whites. However, data regarding such associations are limited for Asians. This study examined associations between tHcy levels and severity of carotid atherosclerosis in Japanese subjects. Additionally, because lacunar infarction is the most prevalent type of ischemic stroke in Japan, we also investigated its associations with tHcy levels. Methods-The subjects were 152 Japanese patients (age, 66.2Ϯ11.0 years) at our hospital. Using ultrasound, we evaluated severity of carotid atherosclerosis by plaque score, which is defined by the sum of all plaque (intima-media thickness Ն1.1 mm) height in bilateral carotid arteries. In 112 of 152 patients, the existence of lacunar infarction was evaluated on brain MRI scans. Results-A moderate linear association was found between tHcy levels and plaque score (rϭ0.48, PϽ0.0001). Moreover, tHcy level was associated with plaque score (␤ϭ0.26, PϽ0.001) independently of traditional atherosclerotic risk factors.In logistic regression analyses, each 1-mol/L-higher tHcy level was associated with a 1.37-fold-higher [95% confidence interval (CI), 1.19 to 1.58] likelihood for lacunar infarction, increasing the likelihood by 1.22-fold (95% CI, 1.04 to 1.43) independently of traditional atherosclerotic risk factors. Conclusions-Higher tHcy levels appear to have associations with increased severity of carotid atherosclerotic plaques and prevalent lacunar infarction in the Japanese. Larger prospective studies are necessary to establish whether higher tHcy levels serve as a harbinger for insidious carotid and cerebrovascular diseases. Key Words: carotid arteries Ⅲ homocyst(e)ine Ⅲ lacunar infarction Ⅲ risk factors E levated plasma total homocysteine (tHcy) levels have been indicated as a risk factor for coronary heart disease, 1-3 ischemic stroke, 4 -6 and peripheral artery disease. 7,8 Also, studies have related tHcy levels to carotid atherosclerosis as a surrogate end point for cardiovascular diseases. 9 -11 However, most of these findings were derived from white populations, and whether such findings also apply for Asians remains to be determined. Additionally, little data are available regarding the relationship between tHcy levels and lacunar infarction, the most prevalent type of ischemic stroke in the Japanese. 12 To quantify carotid atherosclerosis, we have used plaque score and demonstrated its potential utilities for stroke risk assessment. 13,14 This study examined the associations between carotid plaque score and tHcy levels in the Japanese and investigated whether higher tHcy levels are associated with prevalent lacunar infarction as evidenced by brain MRI. Subjects and Methods SubjectsSubjects for this investigation were enrolled from 184 patients consecutively admitted to the National Osaka (Japan) Minami Hospital. All patients had at least 1 of the following diseases: hypertension, diabetes mellitus, hyperlipidemia, ischemic stro...