Hidetaka Hougaku

Ischemic stroke events and carotid atherosclerosis : results of the Osaka follow-up study for ultrasonographic assessment of carotid atherosclerosis (the OSACA study)

BACKGROUND AND PURPOSE To clarify the clinical significance of carotid atherosclerosis for ischemic stroke events, a follow-up study was performed in Japanese patients. METHODS Two hundred fourteen patients were registered from nine hospitals in the Osaka community. All patients were checked for a prior history of stroke, and the risk factors for stroke and atherosclerosis were evaluated. Carotid atherosclerosis was assessed by 7.5-MHz duplex ultrasonography. We studied the relationship between the ischemic stroke event rate and the severity and appearance of the carotid atherosclerosis. We also studied the relationship between stroke events and various risk factors. RESULTS The average duration of follow-up was 16 months. Ten patients suffered new ischemic stroke episodes during this follow-up period. At the initial ultrasonographic study, 16 patients had high-grade stenosis and 21 had ulcerated plaque. Proportional hazard regression analysis showed that grade of stenosis and plaque ulceration were positively related to the event rate. Patients with ulcerated plaque had a sevenfold higher hazard ratio for stroke in comparison to those without (P < .01). The ipsilateral stroke recurrence rate was 11 times higher in patients with ulcerated high-grade stenotic carotid lesions. CONCLUSIONS The present findings demonstrate that the severity of carotid atherosclerosis as evaluated by ultrasonography is a useful indicator of the risk of ischemic stroke in symptomatic patients.

Rate of successful recording of blood flow signals in the middle cerebral artery using transcranial Doppler sonography.

Background and Purpose To assess the usefulness of transcranial Doppler sonography, we investigated the rate of blood flow signal recording failure in the middle cerebral artery in Japanese subjects. Furthermore, we studied the effect of increased emitted power on the rate of successful recording in some of the patients in whom recording failure had been detected at the standard transducer power of 100 mW/cm2. Methods To evaluate the rate of successful recording, we measured blood flow signals in 597 patients (age range, 16 to 89 years) for screening of cerebrovascular disease by using a 2-MHz range-gated, pulsed-wave Doppler instrument at the standard transducer power. In 18 elderly patients with recording failure at the standard power, we assessed the effect of increased emitted power of 400 mW/cm2 on flow signal recording. Results Blood flow signals were recorded in 920 (77.1%) of the 1194 middle cerebral arteries of the 597 patients studied. The rate of successful recording of bilateral middle cerebral artery flow signals (70.9%; 423 of 597 patients) decreased with age, especially in females (17.0% in women aged 70 years or older). In 12 of 18 elderly patients with recording failure at the standard power, blood flow signals could be detected at the increased emitted power of 400 mW/cm2. Conclusions The rate of successful recording of blood flow signals in Japanese subjects decreases with advancing age, especially in females. Increasing the emitted power markedly improves the successful recording rate.

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

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.

Carotid lesions detected by b mode ultrasonography in takayasu's arteritis macaroni sign as an indicator of the disease

Twenty-three patients were studied to evaluate the clinical usefulness of high resolution B-mode ultrasonography in the detection of carotid lesions in patients with Takayasus arteritis. In each patient the carotid arteries were examined using both B-mode ultrasonography (midfrequency of 7.5 MHz) and contrast angiography. In 19 of 23 patients, B-mode ultrasonography clearly demonstrated the characteristic circumferential arterial wall thickening of either one or both sides of the common carotid arteries as a macaroni-like, diffusely thickened intima-media complex. Conversely, contrast angiography demonstrated carotid lesions in only 13 of 23 patients. These results clearly show that B-mode ultrasonography is quite sensitive and superior in the detection of the characteristic thick intima-media complex of the common carotid artery in patients with Takayasus arteritis, when compared with contrast angiography that is usually used for the definitive diagnosis of this disease.

Asymptomatic carotid lesions and silent cerebral infarction

Background and Purpose Few studies have investigated the relationships between asymptomatic carotid lesions and silent infarcts confirmed on magnetic resonance imaging. Methods A consecutive series of 117 subjects (average age, 62±9.4 years) who were free from neurological deficit but had at least one established risk factor for stroke were investigated by B-mode carotid ultrasonography and magnetic resonance imaging of the brain. Carotid lesions were evaluated by plaque score, maximum percent stenosis, and the existence of ulcerated lesions. The relations between the carotid lesions and the incidence, size, or localization of the brain lesions were investigated. Results The incidence of silent infarcts was 42% in all subjects and significantly increased with advancing age (P<.05). Most lesions were smaller than 1 cm in diameter and were usually localized in the subcortical white matter or the basal ganglia. The percentage of subjects with infarcts in- creased significantly as the plaque score increased (P<.05) or when subjects had high-grade stenosis (P<.05) or ulcerated lesions (P<.01). These relationships were also noted in each decade of age. A higher incidence of larger lesions (>1 cm) was found in the brain hemisphere ipsilateral to the carotid lesion, particularly in subjects with high-grade stenosis or ulcerated lesions (P<.01). Multivariate analysis indicated significant correlations with silent infarcts for age, hypertension, and plaque score. Conclusions Both the severity and characteristics of asymptomatic carotid lesions estimated by B-mode ultrasonography were closely related to the appearance of silent infarcts. These results demonstrate that noninvasive assessment of carotid lesions can be useful in predicting the existence of silent cerebral infarction even in patients free from neurological deficits.

Reactivity of cerebral blood flow to carbon dioxide in various types of ischemic cerebrovascular disease: evaluation by the transcranial Doppler method.

Background and Purpose The response of cerebral blood flow to changes in the arterial carbon dioxide partial pressure (i.e., carbon dioxide reactivity) has been evaluated as a parameter of cerebral perfusion reserve in patients with cerebrovascular disease. In this study, variations in this reactivity in various ischemic cerebrovascular diseases were evaluated by a newly established method, a transcranial Doppler technique. Methods Thirty-three patients with symptomatic cerebrovascular disease, 13 patients with asymptomatic cerebral infarction, and 25 age-matched normal control subjects were investigated. The symptomatic patients were divided into three groups; those with unilateral carotid artery obstruction, those with cortical infarction, and those with lacunar infarction. The carbon dioxide reactivity of each subject was determined by simultaneously measuring the mean spatial Doppler frequency in the middle cerebral artery and the end-tidal carbon dioxide partial pressure under normocapnia hypercapnic, and hypocapnic conditions. Results In the patients with carotid obstruction, the carbon dioxide reactivity of the hemisphere ipsilateral to the obstruction was more impaired than the reactivity of the symptomatic hemispheres in any other group, and was significantly less than in the contralateral asymptomatic hemisphere (p<0.01). In patients with cortical infarction, the carbon dioxide reactivity of the symptomatic hemisphere was significantly less than in normal control subjects (p<0.05) and was also less than that of the contralateral asymptomatic hemisphere (p<0.05). In patients with lacunar infarction, the carbon dioxide reactivity of both hemispheres was significantly less than that in normal controls (p<0.01), although there was no difference between the symptomatic and asymptomatic hemispheres. In patients with asymptomatic infarction, the carbon dioxide reactivity was also less than that in normal controls (p<0.01). Conclusions The carbon dioxide reactivity of cerebral blood flow measured by this transcranial Doppler technique may be useful for characterizing the hemodynamic changes that occur in various types of ischemic cerebrovascular disease.

Associations of Serum IL-18 Levels With Carotid Intima-Media Thickness

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. Log-transformed IL-18 concentrations were positively correlated with IMT (r=0.36, P<0.001), and the association remained significant (&bgr;=0.20, P<0.001) 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 serum IL-18 levels appear to be associated with greater carotid IMT, suggesting the link between IL-18 and atherosclerosis.

Higher Levels of Interleukin-6 Are Associated With Lower Echogenicity of Carotid Artery Plaques

Background and Purpose— Echo-lucent carotid plaques can be fragile and vulnerable to rupture, representing a risk factor for ischemic stroke. Given the studies showing that elevated levels of circulating inflammatory markers are predictive of cardiovascular events, we sought to determine whether higher levels of serum interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) are associated with lower echogenicity of carotid plaques. Methods— The study comprised 246 patients who had carotid atherosclerotic plaques as evidenced by ultrasound. Using acoustic densitometry, we quantified the echogenicity of the largest plaque in each patient by integrated backscatter analysis. Serum IL-6 and hsCRP levels were determined in all patients. Results— Both log-transformed IL-6 and hsCRP concentrations were negatively correlated with carotid plaque echogenicity (r =−0.28, P <0.001, and r =−0.14, P <0.05, respectively). When traditional atherosclerotic risk factors, plaque thickness, and medication use were controlled for, IL-6 levels were inversely associated with plaque echogenicity (&bgr;=−0.21, P <0.01), whereas such an association was of borderline significance for hsCRP (&bgr;=−0.12, P =0.06). Conclusions— Higher IL-6 levels, in addition to hsCRP levels, appear to be associated with lower echogenicity of carotid plaques, suggesting a link between inflammation and potential risk of plaques.

Carotid Intima-Media Thickness and Risk of Cardiovascular Events in High-Risk Patients

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.

Reactivity of cerebral blood flow to carbon dioxide in hypertensive patients: evaluation by the transcranial Doppler method.

OBJECTIVE To evaluate hypertensive cerebral involvement before cerebrovascular accidents. DESIGN Cerebral microvascular responses to changes in the arterial partial pressure of CO2 (pCO2; the CO2 reactivity) were compared among patients with different stages and severity of hypertensive disease. PATIENTS Fifty-eight patients with hypertension, 11 with borderline hypertension, 15 hypertensives with cerebral infarction and 58 normotensive controls were studied. METHODS The cerebrovascular CO2 reactivity was determined by measuring simultaneously the end-tidal pCO2 and the blood flow velocity in the middle cerebral artery using transcranial Doppler sonography under hypocapnic, normocapnic and hypercapnic conditions. RESULTS CO2 reactivity was impaired in the hypertensive patients compared with in the normotensive controls, but less so than in the symptomatic hemisphere of the hypertensive patients with cerebral infarction. The CO2 reactivity in the borderline hypertensive patients was greater than that in both the symptomatic and asymptomatic hemispheres of the hypertensive patients with cerebral infarction. In the subjects without cerebral infarction, two risk factors for cerebral atherosclerosis (age and hypertension) were negatively correlated with cerebrovascular CO2 reactivity. In the hypertensive patients age and the estimated duration of hypertension were negatively correlated with cerebrovascular CO2 reactivity. CO2 reactivity in the patients with hypertensive or arteriosclerotic retinopathy or ST-T changes on their electrocardiogram was impaired compared with that in the patients without such changes. CONCLUSIONS Hypertension affected the microvascular reactivity of the brain before the development of cerebrovascular accidents, and its effect varied dependently on the extent of involvement of other target organs.