Interleukin-18 levels are not associated with subclinical carotid atherosclerosis in a community population. The Perth Carotid Ultrasound Disease Assessment Study (CUDAS)

Interleukin (IL)-18 is a novel proinflammatory cytokine that plays a central role in innate and acquired immunity, making it a likely inflammatory candidate in atherosclerosis. We investigated whether circulating IL-18 levels were associated with subclinical atherosclerosis in a community population. Carotid intimal medial thickness (IMT) and carotid plaques were assessed in a cross-sectional study of 1111 randomly selected community subjects, aged 27-77 years. Baseline levels of IL-18, IL-6, high sensitive CRP (hsCRP), fibrinogen and white cell counts were measured along with conventional cardiovascular risk factors. Men had higher mean IL-18 levels than women (P<0.0001). Spearman rank correlations (r(s)) showed that IL-18 was weakly correlated with all inflammatory markers in the whole population (r(s) between 0.11 and 0.23, all P<0.001). IL-18 was also correlated with conventional risk factors including waist-hip ratio, BMI, blood pressure, triglycerides, HDL (inversely) and pack-years smoking (r(s) between 0.18 and 0.39, all P<0.001) but not with LDL-cholesterol. Independent predictors of IL-18 concentrations were waist-hip ratio, HDL, IL-6, hsCRP and hypertension. There was a positive univariate association of IL-18 levels with carotid IMT (P<0.001) and plaque prevalence (P<0.001) but no residual association after adjustment for conventional risk factors (both P>0.05). In a cross-sectional community population, IL-18 levels were related to traditional risk factors and inflammatory markers but were not independently associated with subclinical carotid atherosclerosis.     

慢性肾脏病患者晚期氧化蛋白产物血症及其与动脉粥样硬化的关系

目的　观察慢性肾脏病(CKD)患者循环中晚期氧化蛋白产物(AOPP)水平,并探讨其与动脉粥样硬化的关系。方法　断面队列研究。选109例CKD患者和71例健康对照者,用高分辨B超测颈动脉内膜中层厚度(IMT)、切面内膜中层面积及粥样斑块。测血清AOPP、丙二醛、谷胱苷肽过氧化物酶活性(GSHPx)和C 反应蛋白水平。结果　CKD患者血清AOPP水平明显高于健康对照者(P<0 01), 62例透析者血清AOPP水平明显高于47例未透析者(P<0 01);未透析者血清AOPP水平与内生肌酐清除率呈负相关(r=-0 292, P<0 05)。38例有颈动脉粥样斑块者血清AOPP水平明显高于71例无颈动脉粥样斑块者(P<0 01)。单因素相关分析和多因素逐步回归分析均显示,血清AOPP水平与颈动脉IMT、切面内膜中层面积呈正相关(r=0 332,r=0 288,P值均小于0 05;β=0 313,P<0 001;β=0 301,P<0 01)。CKD患者血清AOPP水平与丙二醛、C 反应蛋白呈正相关(r=0 300,P=0 01;r=0 255,P<0 05 ),与血清GSHPx呈负相关(r=-0 647,P<0 01 )。结论CKD患者普遍存在高AOPP血症,血清AOPP水平随肾功能减退而增高,并与CKD患者动脉粥样硬化密切相关。     

Association of interleukin-6 and C-reactive protein with subclinical carotid atherosclerosis (the Rancho Bernardo Study)

Studies of interleukin-6 (IL-6) and C-reactive protein (CRP) as predictors of atherosclerosis have had mixed results. The purpose of this study was to assess the associations of IL-6 and CRP with the severity of subclinical carotid atherosclerosis measured 12 years later. Participants were 392 adults (56.9% women, mean age 63.2 years) from the Rancho Bernardo Study who had biomarkers measured from 1984 to 1987 and carotid intima-media thickness (IMT) measured from 1996 to 1998. Age-adjusted mean carotid IMT was significantly greater in men than women. After adjusting for traditional cardiovascular risk factors, carotid IMT increased significantly with increasing IL-6 quartiles (p <0.001). In similar analyses, the association between CRP quartiles and carotid IMT was weaker but remained statistically significant (p <0.05). In multiple regression analysis, IL-6 was significantly associated with carotid IMT regardless of CRP. Conversely, CRP was significantly associated with carotid IMT when IL-6 was not included in the model, but this association became nonsignificant when IL-6 was included. In conclusion, baseline IL-6 and CRP were significantly associated with carotid atherosclerosis independent of traditional cardiovascular disease risk factors. The association of IL-6 was independent of CRP, but not vice versa, suggesting an effect of IL-6 on an earlier state of atherosclerosis.     

Carotid artery intima-media thickness and reactive oxygen species formation by monocytes in hypertensive patients

Carotid artery intima-media thickness (IMT) is a widely accepted index for assessing atherosclerosis, and is known to be a risk indicator for cardiovascular and cerebrovascular events. Oxidative stress and inflammation are also known to play critical roles in the pathogenesis of vascular events. We studied the association between IMT and inflammatory markers, such as oxidative stress in polymorphonuclear leukocytes (PMNs) and mononuclear cells (MNCs) in 156 patients with essential hypertension. Reactive oxygen species (ROS) formation by PMNs and MNCs was measured by gated flow cytometry. CRP and traditional risk factors, such as age, gender, body mass index, hemoglobin A(1c), and total cholesterol were also measured. The subjects were divided into a plaque group (max-IMT>or=1.1 mm, n=40), and a nonplaque group (max-IMT<1.1 mm, n=116). ROS formation by MNCs was significantly increased in the plaque group when compared with the nonplaque group (P<0.0001). Multiple regression analysis revealed a significant correlation between IMT and ROS formation by MNCs (r=0.407, P<0.0001), or CRP (r=0.216, P=0.0029) or hemoglobinA1c (r=0.158, P=0.0270) or age (r=0.157, P=0.0447). No significant correlation was observed between IMT and ROS formation by PMNs. These results suggest that carotid artery IMT may be affected by increased ROS formation by MNCs, and that increased ROS formation by MNCs may be related to the development of atherosclerosis. We propose that ROS formation by MNCs is a marker for prediction of carotid atherosclerosis.     

Significance of serum circulating hepatocyte growth factor in the development of carotid atherosclerosis

We investigated the relation between the serum concentration of HGF and carotid atherosclerosis. Serum concentrations of HGF were measured in 128 in-patients (mean age, 74 +/- 11 years) free from cardiac, liver and renal diseases, in addition to lung diseases, in the Medical Department of Nomura Municipal Hospital between August, 2000 and June, 2001. Carotid intima-media thickness (IMT) was evaluated by ultrasonography with a 7.5 MHz linear type B-mode probe. The results showed a significantly positive correlation between serum age and HGF concentrations in patients with carotid atherosclerosis (IMT > 1.0 mm) (r = 0.391, p = 0.005). On the other hand, there was no significant correlation between age and serum HGF concentration in those without carotid atherosclerosis (IMT 相似文献   

Aortic stiffness, flow-mediated dilatation and carotid intima-media thickness in obstructive sleep apnea: non-invasive indicators of atherosclerosis

BACKGROUND AND OBJECTIVE: Obstructive sleep apnea (OSA) has a critical association with cardiovascular mortality and morbidity. Carotid intima-media thickness (IMT), flow-mediated dilatation (FMD) and aortic stiffness are early signs of atherosclerosis. The presence of subclinical atherosclerosis was assessed in OSA patients using these parameters. METHODS: 40 patients with OSA showing an apnea-hypopnea index (AHI) > or =5 (mean age 51.3 +/- 9 years, 32 males) and 24 controls (AHI < 5, mean age 51.9 +/- 5.2 years, 19 males) were enrolled in the study. In all subjects, polysomnographic examination and recordings were performed during sleep. IMT of the carotid artery, endothelium-dependent/-independent vasodilation of the brachial artery and aortic elastic parameters were investigated using high-resolution Doppler echocardiography. RESULTS: The demographic data of the patients with OSA and controls were not significantly different. Subjects with OSA demonstrated higher values of aortic stiffness (7.1 +/- 1.88 vs. 6.42 +/- 1.56, respectively) and IMT (0.85 +/- 0.13 vs. 0.63 +/- 0.11 mm, p = 0.0001, respectively) but lower distensibility (9.47 +/- 1.33 vs. 11.8 +/- 3.36 cm(2)/dyn/10(6)) and FMD (4.57 +/- 1.3 vs. 6.34 +/- 0.83%, p = 0.0001, respectively) than the controls. The respiratory disturbance index correlated positively with aortic stiffness and IMT and negatively with distensibility and FMD. CONCLUSION: We observed blunted endothelium-dependent dilatation, increased carotid IMT and aortic stiffness in patients with OSA compared with matched control subjects. This is evident in the absence of other diseases, suggesting that OSA is an independent cause of atherosclerosis. These simple and non-invasive methods help to detect subclinical atherosclerosis in OSA.     

2型糖尿病患者血清炎性因子与颈动脉粥样硬化的相关性研究

目的 研究2型塘尿病患者血清炎性因子水平与颈动脉粥样硬化的关系.方法 选择124例2型糖尿病患者,采用酶联免疫吸附法测定血清内皮细胞猫附分子1（ICAM-1）、血管细胞黏附分子1（VCAM-1）,E选择素、白细胞介素6（IL-6）和C反应蛋白（CRP）水平;按颈动脉超声检查结果将糖尿病患者分为颈动脉正常组（38例）、颈动脉增厚组（40例）和颈动脉斑块组（46例）.选择40例健康体检者作为对照组,比较各组血清炎性因子水平.结果 ①颈动脉正常组血清ICAM-1,IL-6及CRP较对照组升高,颈动脉增厚组ICAM-1、VCAM-1、IL-6及CRP水平高于颈动脉正常组,颈动脉斑块组ICAM-1、VCAM-1、E选择素高于颈动脉增厚组,上述指标各组差异均有统计学意义,P 〈0.05,或P〈0.01.②相关性分析显示,颈动脉内-中膜厚度（IMT）增厚程度与糖化血红蛋白（HbAlc）（r=0.472）、ICAM-1（r=0.501）、VCAM-1（r = 0.484）、E选择素（r＝0.289）、IL-6（r=0.425）及CRP（r=0.381）呈正相关.患者HbAlc与ICAM-1、VCAM-1、IL-6及CRP呈正相关.ICAM-1、VCAM-1、E选择素、IL-6、CRP间呈正相关,均P〈0.01或P〈0.05.结论 炎性反应参与了2型糖尿病患者颈动脉粥样硬化的发病过程,血清炎性因子水平可以在一定程度上反映糖尿病患者的颈动脉粥样硬化程度.     

Carotid atherosclerosis as a risk factor for complex aortic lesions in patients with ischemic cerebrovascular disease.

Aortic arch atherosclerotic lesions can cause ischemic cerebrovascular disease (ICVD). The association between carotid and aortic atherosclerosis was examined, and it was investigated whether noninvasive carotid evaluation aids in the identification of aortic lesions as potential ICVD risk. The subjects comprised 147 patients with ICVD who had undergone carotid ultrasonography and transesophageal echocardiography. Carotid and aortic arch atherosclerosis was evaluated by measuring the maximum intima - media thickness (IMT), with aortic IMT of at least 4 mm, mobile plaques and/or ulcers defined as complex aortic lesions with potential ICVD risk. Carotid IMT was linearly associated with aortic IMT (r=0.53, p<0.001), and the association was independent of traditional cardiovascular risk factors (beta =0.36, p<0.001). Also, each 1 SD greater carotid IMT was associated with 4.2-fold (95% confidence interval: 2.5-7.0) higher likelihood of complex aortic lesions, with the likelihood little modified when controlling for cardiovascular risk factors. In particular, complex aortic lesions were found in 78% of patients with the highest carotid IMT tertile, compared with 14% of those with the lowest tertile (p<0.05). Based on these findings, carotid atherosclerosis is associated with aortic atherosclerosis, representing a risk factor for aortic lesions that are a potential ICVD risk.     

Association between serum gamma-glutamyltransferase activity and carotid intima-media thickness

Serum gamma-glutamyltransferase (GGT) activity is a marker of oxidative stress and activity is associated with cardiovascular disease. Carotid intima-media thickness (IMT) is a noninvasive predictor of atherosclerosis. We investigated the association between serum GGT activity and carotid IMT. Fifty-five persons who had normal liver function tests were consecutively enrolled. Carotid IMT was evaluated in the right and left common carotid arteries. The averaged values of carotid IMT and serum GGT activity were compared. Serum GGT activity correlated with carotid IMT (r = .396, P = .003). Serum GGT activities were increased in patients with carotid intimal hyperplasia compared with those without intimal hyperplasia (20.3 ± 11.2 vs 34.3 ± 16.1 U/L; P = .001). Serum GGT activity is associated with carotid IMT. This finding supports the concept that elevated serum GGT activity is a marker of atherosclerosis.     

Inverse relationship between adiponectin levels and subclinical carotid atherosclerosis in patients undergoing coronary artery bypass grafting

The purpose of this study was to examine the relation between adiponectin levels and subclinical carotid atherosclerosis in patients undergoing coronary artery bypass grafting (CABG). Serum concentrations of adiponectin and carotid intima/media thickness (IMT) were measured in 84 consecutive patients who underwent CABG. Carotid IMT both at the common carotid artery and carotid bulb level was correlated negatively and significantly (r = -0.581 and r = -0.415, respectively, P < 0.01) with the serum concentrations of adiponectin. Linear regression modeling identified adiponectin as the strongest predictive variable for carotid IMT both at the common carotid artery and carotid bulb level (P < 0.001). Stepwise regression analyses also showed that adiponectin was the strongest independent determinant of the carotid IMT both at the common carotid artery and the carotid bulb level (F = 20.215 and F = 19.565, respectively, P < 0.001). The mean number of diseased coronary arteries, mean number of distal anastomoses, cardiopulmonary bypass time, and aortic cross-clamping time did not significantly correlate with the serum concentrations of adiponectin. The findings indicate the presence of an inverse relationship between serum concentrations of adiponectin and subclinical carotid atherosclerosis in patients undergoing CABG. In these patients, the absence of a significant correlation between severity of coronary atherosclerosis and adiponectin might suggest that adiponectin levels may predict the early stages rather than further progression of atherosclerosis.     

Association between carotid atherosclerosis and markers of inflammation in rheumatoid arthritis patients and healthy subjects

OBJECTIVE: To examine the relationship between markers of systemic inflammation and carotid atherosclerosis in patients with rheumatoid arthritis (RA) and healthy controls. METHODS: Carotid artery intima-media thickness (IMT) and carotid plaque were measured using high-resolution B-mode ultrasound in 204 patients with RA, ages 40-85, and 102 age- and sex-matched healthy persons. No subject in either group had ever smoked cigarettes. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were used to measure systemic inflammation. The relationship of the carotid artery IMT and carotid plaque to inflammation markers was examined, adjusting for age, sex, RA versus control status, and the cardiovascular (CV) risk factors hypercholesterolemia, systolic blood pressure, diabetes mellitus, and body mass index (BMI). RESULTS: A significant linear trend for increased carotid artery IMT was associated with increasing ESR and CRP categories (r = 0.16, P = 0.004 for ESR, and r = 0.13, P = 0.02 for CRP). These trends did not differ among RA cases and controls, and were independent of age, sex, and CV risk factors. The difference in carotid artery IMT between the lowest and highest categories of ESR was 0.221 mm (95% confidence interval [95% CI] 0.767-1.020, P = 0.02). The difference between extreme CRP categories was 0.275 mm (95% CI 0.039-0.509, P = 0.02). Both remained significant after CV risk factor adjustment. Carotid plaque displayed a similar relationship to markers of inflammation. CONCLUSION: Increased carotid artery IMT and the presence of carotid plaque are associated with markers of systemic inflammation in patients with RA and in healthy subjects. This observation is consistent with hypotheses that assign a role to systemic inflammation in atherosclerosis, and may have implications regarding RA and other chronic inflammatory diseases.     

IgG antibodies against food antigens are correlated with inflammation and intima media thickness in obese juveniles.

OBJECTIVE: Systemic low grade inflammation may contribute to the development of obesity, insulin resistance, diabetes mellitus and atherosclerotic vascular disease. Food intolerance reflected by immunoglobulin G (IgG) antibodies may predispose to low grade inflammation and atherogenesis. We examined the relationship between IgG antibodies specific for food components, low grade inflammation and early atherosclerotic lesions in obese and normal weight juveniles. RESEARCH METHODS AND PROCEDURES: We determined IgG antibodies directed against food antigens, C-reactive protein (CRP) and the thickness of the intima media layer (IMT) of the carotid arteries in 30 obese children and in 30 normal weight children. RESULTS: Obese juveniles showed a highly significant increase in IMT (p=0.0001), elevated CRP values (p=0.0001) and anti-food IgG antibody concentrations (p=0.0001) compared to normal weight juveniles. Anti-food IgG showed tight correlations with CRP (p=0.001/r=0.546) and IMT (p=0.0001/r=0.513) and sustained highly significant in a multiple regression model. DISCUSSION: We show here, that obese children have significantly higher IgG antibody values directed against food antigens than normal weight children. Anti- food IgG antibodies are tightly associated with low grade systemic inflammation and with the IMT of the common carotid arteries. These findings raise the possibility, that anti-food IgG is pathogenetically involved in the development of obesity and atherosclerosis.     

Serum levels of vascular endothelial growth factor are elevated in patients with obstructive sleep apnea and severe nighttime hypoxia.

Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality; however, some patients with OSA do not develop cardiovascular disease even in the presence of severe nocturnal oxygen desaturations. Vascular endothelial growth factor (VEGF) is a hypoxia-sensitive glycoprotein stimulating neoangiogenesis. We hypothesized that VEGF production is increased in OSA because of repetitive nocturnal hypoxia. Three different groups were investigated: 10 OSA patients with severe nighttime hypoxia (Group A), 10 OSA patients with moderate hypoxia (Group B), and 10 healthy volunteers (Group C). Serum levels of VEGF were measured by ELISA from peripheral venous blood samples obtained at 7 AM. Group A had significantly (p < 0.01) increased VEGF serum levels when compared with Group B and Group C (mean +/- SEM: 410 +/- 77 pg/ml versus 224 +/- 38 pg/ml and 245 +/- 61 pg/ml). The degree of nocturnal oxygen desaturation in OSA significantly correlated with the VEGF concentrations (r = 0.67, p < 0.01). In conclusion, serum levels of VEGF are elevated in severely hypoxic patients with OSA and are related to the degree of nocturnal oxygen desaturation. This might constitute an adaptive mechanism to counterbalance the emergence of OSA-related cardiovascular disease.     

Effect of transdermal hormone replacement therapy on carotid artery wall thickness and levels of vascular inflammatory markers in postmenopausal women.

Carotid intima-media thickness (IMT) and vascular inflammatory markers have been shown to be involved in atherosclerosis. This study was designed to investigate the effect of transdermal hormone replacement therapy (HRT) on carotid IMT and vascular inflammatory markers in postmenopausal women and to explore the interrelationship between the change in carotid IMT and the changes in vascular inflammatory markers. Thirty-five postmenopausal women (mean age 57.0+/-7.7 years) received transdermal HRT (continuous 17beta-estradiol patch [36 microg/day] plus cyclic oral medroxyprogesterone acetate [2.5 mg/day, for 12 days/ month]) for 12 months, and 32 controls (mean age 58.0+/-7.5 years) did not. Carotid IMT, assessed by ultrasound, and circulating vascular inflammatory markers, i.e., C-reactive protein (CRP), intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, E-selectin, monocyte chemoattractant protein (MCP)-1, and matrix metalloproteinase (MMP)-9 were measured before and after 12 months of treatment. In the HRT group, carotid IMT decreased significantly (p<0.01), from 0.71+/-0.13 mm to 0.65+/-0.12 mm, and the ICAM-1, VCAM-1, E-selectin, and MCP-1 levels decreased significantly (p<0.01 for all), but the CRP and MMP-9 levels remained unchanged. Carotid IMT and vascular inflammatory markers were unchanged in the control group. In the HRT group, the change in carotid IMT was significantly correlated with the change in serum E-selectin (r=0.38, p<0.05), but not with the changes in other vascular inflammatory markers. These results suggest that transdermal HRT reduced carotid artery wall thickness, and that the reduction may have been induced by an antiatherosclerotic effect combined with the direct effect of estrogen and decreased levels of estrogen-induced E-selectin.     

Carotid and femoral B-mode ultrasound intima-media thickness measurements in adult post-coarctectomy patients.

AIM: Cardiovascular and cerebrovascular morbidity and mortality in adult post-coarctectomy patients is increased even after successful surgical repair of the aorta. B-mode ultrasound intima-media thickness (IMT), a validated marker for atherosclerosis and vascular disease risk, was used to measure pre-coarctatial carotid and post-coarctatial femoral arterial wall changes in these patients. METHODS: Measurements were done in 131 patients (mean age 31.6 y [SD 11.3 y]; 78 were normotensive, 53 were hypertensive) and in 26 controls (30.9 y [SD 9.4 y]). RESULTS: Age, serum lipids and smoking history were similar in patients and controls. Overall, IMT in patients and controls were similar (0.59 mm [SD 0.14 mm] and 0.59 mm [SD 0.08 mm]. In patients, carotid IMT was increased (0.67 mm [SD 0.12 mm] vs 0.61 mm [SD 0.08 mm] in controls: p=0.01); femoral IMT was decreased (0.48 mm [SD 0.09 mm] vs 0.57 mm [SD 0.07 mm]: p=0.001). In normotensive patients carotid IMT was not increased (0.64 mm [SD 0.12 mm] vs 0.61 mm [SD 0.08 mm]: p=0.2), but patients showed a higher SD. Carotid IMT in hypertensive patients was increased (0.72 mm [SD 0.12 mm] vs 0.64 mm [SD 0.11 mm] in normotensive patients: p<0.001). The femoral IMT in normo- and hypertensives patients were similar (0.48 mm [SD 0.09 mm] and 0.49 mm [SD 0.10 mm]: p=0.12). Carotid IMT in patients with aortic coarction and age at surgery were associated (r=0.36, p<0.0001), where femoral IMT is not. CONCLUSION: Early peripheral arterial wall damage is prominent in hypertensive post-coarctatial patients and is limited to pre-coarctatial conduits. The decreased femoral IMT in all patients may indicate a relatively low post-coarctatial blood pressure if pressure control is guided according to pre-coarctatial RR. Pre-coarctatial arterial wall change is less apparent in post-coarctectomy patients who have a controlled blood pressure and who had early surgical repair.     

Interleukin 6 is associated with subclinical atherosclerosis: a link with soluble intercellular adhesion molecule 1

BACKGROUND: Among the markers of inflammation, a cytokine, interleukin (IL)-6, promotes the expression of intercellular adhesion molecule 1 (ICAM-1), C-reactive protein (CRP) synthesis, and leads to a series of procoagulant actions with potential major implications on the progression of atherosclerosis. AIM OF THE STUDY: To analyse in a population-based study, the relationship between IL-6 and atherosclerotic lesions and the role of serum ICAM-1 and CRP on this relationship. POPULATION: Among 1015 individuals randomly recruited between 1995 and 1997 in Haute-Garonne, a French region with a low cardiovascular risk, 953 subjects with complete data for all measurements were analysed. Common carotid intima-media thickness (IMT) and the presence of plaques in the carotid and femoral arteries were assessed by ultrasonography. RESULTS: Quartiles of IL-6, serum ICAM-1 and CRP were positively associated with plaques and IMT. After adjustment for traditional risk factors, IL-6 (P < 0.001) and serum ICAM-1 (P < 0.002) remained positively associated with plaques but not CRP (P = 0.20). Neither IL-6, nor serum ICAM-1, nor CRP were independently associated with IMT. When serum ICAM-1 was entered into the model in addition to traditional risk factors and IL-6, the percentage of variance in the number of plaques explained by the model did not increase significantly. CONCLUSION: IL-6 levels are associated with subclinical atherosclerotic lesions independently of traditional risk factors; the influence of IL-6 on ICAM-1 secretion may play a role in this association. These results argue the interest of IL-6 in the stratification of cardiovascular risk.     

Carotid atherosclerosis is associated with brain atrophy in Japanese elders

BACKGROUND: The relation between atherosclerosis and brain atrophy remains unclear in patients with risk factors for cardiovascular diseases. OBJECTIVE: This study was performed to clarify the relation between brain atrophy and carotid atherosclerosis. METHODS: A total of 142 patients (78 women and 64 men, mean age 74 years) with no neurologic disturbances were studied. Brain atrophy was evaluated on the basis of the brain atrophy index (BAI, BAI = brain parenchyma/intracranial space A 100%), calculated by means of digitized computed tomographic scans obtained at the level of the basal ganglia. Carotid atherosclerosis was evaluated on the basis of the plaque score (PS), defined as the sum of all plaque heights in both carotid arteries, intima-media thickness (IMT), and vessel diameter (VD) of the common carotid artery as assessed by ultrasonography. RESULTS: Age negatively correlated with BAI in both men (r = -0.587, p < 0.001) and women (r = -0.724, p < 0.001). PS of the carotid artery also negatively correlated with BAI in men (r = -0.502, p < 0.001) as well as women (r = -0.480, p < 0.001). VD and IMT of the right carotid artery negatively correlated with BAI in women (VD; -0.256, p < 0.05, IMT; -0.216, p < 0.05) but not in men. Other characteristics were unrelated to BAI. Multiple regression analysis showed that age and PS were independent predictors of brain atrophy in both sexes. The percentage of variance of BAI values explained by this model in women (51.9%) was much greater than that in men (35.5%). CONCLUSION: Carotid atherosclerosis may be a useful morphological index of brain atrophy.     

Carotid intima-media thickness by B-mode ultrasound as surrogate of coronary atherosclerosis: correlation with quantitative coronary angiography and coronary intravascular ultrasound findings.

AIMS: Although well supported by postmortem studies, the reliability of carotid atherosclerosis as surrogate marker of coronary atherosclerosis has been put in doubt by in vivo studies showing a poor correlation between carotid intima-media thickness (IMT) detected by external carotid ultrasound (ECU) and coronary stenosis assessed by quantitative coronary angiography (QCA). In the present study, we have investigated whether a stronger in vivo correlation between the two arteries can be obtained by using homogeneous variables such as carotid and coronary IMT, detected by ECU and intravascular ultrasound (IVUS), respectively. METHODS AND RESULTS: ECU, QCA, and IVUS measurements were made in 48 patients. Carotid IMT was correlated with both angiographic and IVUS findings. A significant but weak correlation was observed between ECU and QCA variables (r approximately 0.35, P < 0.05); the correlation between ECU and IVUS measurements of IMT was higher, with correlation coefficients ranging from 0.49 to 0.55. In patients with a QCA diagnosis of normal/intermediate coronary atherosclerosis, the presence of a carotid-IMT(mean) > 1 mm was associated with an 18-fold increase in risk of having a positive IVUS test (OR = 17.99, 95% CI 1.83-177.14, P= 0.013) and with a seven-fold increased risk of having a significant IVUS coronary stenosis (OR = 7.4, 95% CI 1.27-44.0, P = 0.028). CONCLUSION: Carotid atherosclerosis correlates better with coronary atherosclerosis when both circulations are investigated by the same technique (ultrasound) using the same parameter (IMT). This supports the concept that carotid IMT is a good surrogate marker of coronary atherosclerosis.     

慢性肾衰竭患者高同型半胱氨酸血症、氧化应激和微炎症反应间的关系及其在动脉粥样硬化中的作用

目的　探讨同型半胱氨酸 (Hcy)血症和氧化应激、微炎症反应之间的关系 ,及其在慢性肾衰竭 (CRF)患者动脉粥样硬化 (AS)形成中的作用。方法　测 114例CRF患者 (CRF组 ,其中 6 2例行血液透析 ,非透析治疗 5 2例 )和 37例健康对照者 (健康对照组 )血浆总Hcy(tHcy)水平、循环丙二醛 (MDA)、谷胱苷肽过氧化物酶活性 (GSHPx)及血清C 反应蛋白 (CRP)、白细胞介素 (IL) 6、肿瘤坏死因子 (TNF)α水平 ,高分辨超声技术测颈动脉内膜 中层厚度 (IMT)及粥样硬化斑块。结果　非透析CRF患者血浆tHcy、MDA、CRP和TNFα水平高于健康对照组 ,且随肾功能损害程度的加重而升高 ,GSHPx则低于健康对照组 ;血液透析患者tHcy、MDA、CRP、IL 6和TNFα水平均高于非透析患者 ,GSHPx进一步降低。CRF患者IMT增厚阳性率、平均IMT及颈动脉粥样斑块检出率明显高于健康对照组。动脉病变越重 ,血浆tHcy、MDA及CRP水平越高 ,GSHPx越低。多因素逐步回归分析显示 ,tHcy、MDA、CRP、血糖和极低密度脂蛋白水平是影响颈总动脉IMT的危险因素 (R2 =0 5 72 ,P<0 0 0 1) ,影响CRF患者血浆MDA水平的因素有血浆GSHPx、tHcy、血肌酐 ,影响CRF患者血清CRP水平的因素有血清IL 6、TNFα、MDA、血浆白蛋白。结论　Hcy血症可能参与了CRF患者氧化应激的发生     

Plasma interleukin (IL)-18 concentrations is elevated in patients with previous myocardial infarction and related to severity of coronary atherosclerosis independently of C-reactive protein and IL-6

AIM: Interleukin-18 (IL-18) is a pro-inflammatory cytokine with a central role in the inflammatory cascade. In the present study, we investigated whether patients with precocious myocardial infarction have higher plasma IL-18 concentrations than matched controls. Furthermore, the relationships between plasma IL-18 concentrations and coronary atherosclerosis, C-reactive protein (CRP), interleukin-6 (IL-6) and traditional cardiovascular risk factors were examined. METHODS AND RESULTS: Three hundred eighty-seven unselected survivors of a first myocardial infarction aged less than 60 years and 387 sex and age matched controls were enrolled in the study. A subset of patients (n=236) was evaluated by quantitative coronary angiography. Postinfarction patients had significantly higher mean level of plasma IL-18 than controls (309.6+/-138.6 versus 285.4+/-115.7pg IL-18/mL). Furthermore, plasma IL-18 concentration was significantly associated with coronary plaque area (r=0.17, p=0.009). This relationship remained in a partial correlation analysis adjusting for CRP (r=0.15, p=0.02), for IL-6 (r=0.15, p=0.02) and for both CRP and IL-6 (r=0.15, p=0.02). In addition, IL-18 levels were significantly associated with other cardiovascular risk factors, namely age, low density lipoprotein (LDL) cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, insulin, proinsulin, body mass index (BMI), systolic and diastolic blood pressure. CONCLUSION: The present work provides evidence that plasma IL-18 is increased in postinfarction patients and is associated with coronary atherosclerosis.