Homocysteine and carotid atherosclerosis in chronic renal failure--the confounding effect of renal function

Since total homocysteine (tHcy) level is markedly elevated in patients with chronic renal failure (CRF), it has been presented as a potential factor contributing to the high risk of cardiovascular disease (CVD) in CRF. Our aim was to examine the significance of elevated tHcy level and other cardiovascular risk factors for carotid atherosclerosis in patients with CRF. In this cross-sectional study, 135 study patients with CRF (52 +/- 11 years) included 58 patients with moderate to severe predialysis CRF, 36 dialysis patients and 41 renal transplant recipients. In addition, 58 control subjects were examined. The association of tHcy level and classic risk factors for atherosclerosis with common carotid artery intima-media thickness (IMT) or carotid artery plaque score was examined. We found no association between tHcy and carotid IMT or a high carotid plaque score in the CRF patient groups. No consistent association was found between elevated tHcy and coronary artery disease, cerebrovascular disease or peripheral arterial disease. Renal function, described as creatinine clearance, was the strongest determinant for tHcy level. Significant predictors of carotid atherosclerosis were age, duration of hypertension and elevated low-density lipoprotein cholesterol level. In conclusion, the present study shows no apparent association between tHcy level and atheromatous carotid findings in patients with CRF. However, because of the changing renal function in the course of renal disease, the strong confounding effect of renal function may not be adequately controlled for the analysis of the significance of elevated tHcy level for CVD in patients with CRF.     

Association between plasma homocysteine concentration and carotid atherosclerosis in hemodialysis patients.

Accelerated atherosclerosis is a major risk for uremic patients undergoing long-term hemodialysis. Because hyperhomocysteinemia may influence this condition, 168 such patients were examined for a possible association between plasma total homocysteine concentration (tHcy) and conventional cardiovascular risk factors. Generalized atherosclerosis was indicated by excessive intimal-medial wall thickness (IMT) of the extracranial carotid artery as measured by B-mode ultrasonography. The results documented tHcy in these patients of 33.0+/-16.9 micromol/L, a significantly higher amount than that of healthy subjects (11.0+/-3.1 micromol/L, p<0.0001). The patients' carotid maximum IMT was 1.79+/-1.16 mm. In multiple regression analyses with forward elimination procedure, carotid maximum IMT was clearly related to age (r = 0.417, p<0.0001), systolic blood pressure (r = 0.262, p = 0.0043), smoking (r = 0.177, p = 0.0076), duration of hemodialysis (r = 0.083, p = 0.0045), and tHcy (r = 0.195, p = 0.0021). These 5 factors accounted for 36.0% of the variation in carotid maximum IMT. Factors determined as unrelated were male gender, diastolic blood pressure, body mass index, total and HDL cholesterol, triglyceride, lipoprotein(a), uric acid, calcium, inorganic phosphate, and parathyroid hormone. Therefore hyperhomocysteinemia, along with advanced age, systolic hypertension and smoking aggravates atherosclerosis in chronic uremic patients.     

Plasma total homocysteine level and its association with carotid intima-media thickness in obesity

BACKGROUND: Elevated plasma concentrations of total homocysteine (tHcy) and obesity are risk factors for cardiovascular disease. The relationship between hyperhomocysteinemia and obesity has not been totally elucidated. OBJECTIVE: The first aim of the study was to investigate whether anthropometric measurements and insulin resistance contribute to the variation in homocysteine levels in obese adults. Our second aim was to determine if any relationship exists between the carotid intima-media thickness (IMT) and plasma tHcy levels in obese subjects without traditional cardiovascular risk factors. MATERIAL AND METHODS: Fifty-five obese (15 male, 40 female) and 30 (11 male, 19 female) age- and sex-matched apparently healthy volunteers were included. Exclusion criteria were smoking, hypertension, diabetes, vitamin ingestion, hyperlipidemia, renal failure, liver disease, pregnancy, menopause and secondary obesity such as Cushing's syndrome, hypothyroidism. tHcy, folate, vitamin B12 levels, fasting insulin, glucose, total cholesterol, triglycerides, HDL, LDL particles, uric acid, creatinine and creatinine clearance were measured. Non-invasive ultrasound measurements of carotid IMT were performed. RESULTS: tHcy levels and carotid IMT were comparable between obese and non-obese subjects. Waist/hip ratio (WHR) was related to tHcy and carotid IMT. Hyperhomocysteinemic subjects (tHcy >19.2 micromol/l) had greater WHR than normo-homocysteinemic subjects. Both tHcy levels and carotid IMT were higher in male subjects both in obese and non-obese subjects. No association was observed between insulin resistance and tHcy and carotid IMT. Renal function and abdominal obesity were significant predictors of plasma tHcy levels. CONCLUSIONS: We concluded that, in obese subjects who are free from atherosclerosis and impaired renal function, plasma tHcy levels do not differ from healthy subjects. Plasma tHcy concentrations are not related to carotid IMT in obese subjects during the non-atherogenic stage. Although no significant difference was observed between insulin-resistant and insulin-sensitive subjects compared to the plasma tHcy levels, the relationship between tHcy levels and some components of the insulin resistance syndrome may support the opinion that tHcy may be considered a component of the insulin resistance syndrome.     

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.     

Antioxidant vitamins and the risk of carotid atherosclerosis : The perth carotid ultrasound disease assessment study (CUDAS)

OBJECTIVES

This study examined whether dietary intake or plasma levels of antioxidant vitamins were independently associated with common carotid artery intima-media (wall) thickness (IMT) or focal plaque, or both, in a large, randomly selected community population.

BACKGROUND

Oxidation of low-density lipoprotein (LDL) cholesterol is thought to be important in early atherogenesis. Antioxidant micronutrients may therefore protect against lipid peroxidation and atherosclerotic vascular disease.

METHODS

We studied 1,111 subjects (558 men and 553 women; age 52 ± 13 years [mean ± SD], range 27 to 77). We measured dietary vitamin intake and fasting plasma levels of vitamins A, C and E, lycopene and alpha- and beta-carotene and performed bilateral carotid artery B-mode ultrasound imaging.

RESULTS

After adjustment for age and conventional risk factors, there was a progressive decrease in mean IMT, with increasing quartiles of dietary vitamin E intake in men (p = 0.02) and a nonsignificant trend in women (p = 0.10). Dietary vitamin E levels accounted for 1% of the variance in measured IMT in men. For plasma antioxidant vitamins, there was an inverse association between carotid artery mean IMT and plasma lycopene in women (p = 0.047), but not in men. None of the other dietary or plasma antioxidant vitamins, nor antioxidant vitamin supplements, were associated with carotid artery IMT or focal carotid artery plaque.

CONCLUSIONS

This study provides limited support for the hypothesis that increased dietary intake of vitamin E and increased plasma lycopene may decrease the risk of atherosclerosis. No benefit was demonstrated for supplemental antioxidant vitamin use.     

Low concentrations of folate, not hyperhomocysteinemia, are associated with carotid intima-media thickness

AIM: We examined whether total homocysteine, B vitamins and the 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism are related to common carotid intima-media thickness, a marker of atherosclerosis, and carotid distension, a marker of arterial stiffness. METHODS: We used cross-sectional data from 819 individuals aged 50-70 years. B-mode ultrasound of the distal common carotid arteries was performed to determine maximum carotid intima-media thickness, mean carotid intima-media thickness and distension. RESULTS: Carotid intima-media thickness and distension did not differ across homocysteine, serum folate, vitamin B(6) and vitamin B(12) quartiles or between MTHFR C677T genotype. Erythrocyte folate was independently associated with maximum carotid intima-media thickness (mean difference first versus third quartile, 0.03 mm, 95% CI 0.004-0.06 mm; first versus fourth quartile, 0.03 mm, 95% CI -0.002 to 0.06 mm). Further adjustment for homocysteine did not affect this association. Folate deficient subjects had greater maximum carotid intima-media thickness than those with high-normal folate concentrations (serum folate: mean difference 0.05 mm, 95% CI 0.01-0.08 mm; erythrocyte folate: mean difference 0.04 mm, 95% CI -0.03 to 0.11 mm). CONCLUSION: Low folate concentrations, independent of hyperhomocysteinemia, may promote atherogenesis. Our findings confirm the null association of homocysteine with carotid intima-media thickness observed in other population-based studies, suggesting that hyperhomocysteinemia does not perpetuate atherosclerosis or arterial stiffness.     

Atherosclerotic calcification and intimal medial thickness of the carotid arteries

BACKGROUND AND PURPOSE: Carotid intimal medial thickness (IMT) is a measure of subclinical atherosclerosis and is predictive of future cardiovascular events. The purpose of this study was to determine the significance and magnitude of association between IMT and atherosclerotic calcification of the carotid arteries. METHODS: Forty-five subjects underwent electron beam computed tomography of the neck to ascertain the extent of atherosclerotic calcification in the carotid arteries followed by B-mode carotid ultrasonography for IMT. RESULTS: The mean age, BMI and total cholesterol to HDL ratio were 61.4, 26.2 and 4.3, respectively. Forty-one percent were women. The overall mean IMT was 0.91 mm with the mean for the right and left being 0.93 and 0.87 mm, respectively. The median total carotid calcium score (CCS) was 48.4 [range: 0-973]. Age-adjusted correlations were significant between the overall mean IMT and total CCS (r=0.53, p<0.01), mean right IMT and right CCS (0.31, 0.05), mean left IMT and left CCS (0.31, 0.05), right common carotid IMT and right CCS (0.53, <0.01) and left common carotid IMT and left CCS (0.31, 0.05). The mean IMT was 0.14 mm greater in subjects with any carotid calcification adjusted for risk factors. A 0.05 mm increase in the carotid IMT was associated with an approximate 3-fold increase in risk for the presence of atherosclerotic calcification. CONCLUSIONS: Carotid IMT is significantly correlated with and predictive of atherosclerotic calcification. Conversely, individuals with any carotid calcification have significantly greater intimal medial thicknesses.     

尿毒症血液透析患者高同型半胱氨酸血症与动脉粥样硬化关系的研究

目的探讨尿毒症血液透析患者血浆同型半胱氨酸浓度与动脉粥样硬化的关系。方法对北京朝阳医院血液透析中心2003-10~2004-01采用荧光偏振免疫分析法测定血浆总同型半胱氨酸(tHcy)浓度,应用彩色多普勒超声诊断仪检测颈动脉内膜-中层厚度(IMT),并根据公式计算颈动脉Young弹性指数、斑块阳性率,用免疫化学发光法测定血清叶酸、VitB12浓度。结果尿毒症血液透析患者高同型半胱氨酸血症发生率为68.3%,尿毒症血液透析患者血清叶酸和VitB12浓度与血浆tHcy呈负相关。IMT、颈动脉Young弹性指数、斑块阳性率与血浆tHcy浓度呈正相关(r分别为0.34,0.31,0.23,P均<0.05),这种相关性在应用多元Logistic回归剔除了性别、年龄、血压、血脂、血糖、血红蛋白等因素影响后仍然存在。结论高同型半胱氨酸血症可能是尿毒症血液透析患者发生动脉粥样硬化的独立危险因素。     

Measurement of pulse wave velocity: site matters

BACKGROUND: Aortic pulse wave velocity (PWV) predicts mortality from cardiovascular disease, ischaemic heart disease and stroke. However, a comparison of associations between PWV measured at different sites and atherosclerosis in coronary, carotid and femoral arteries has not been made. METHODS: In 159 men (ages 45-82 years) with and without known coronary artery disease, PWV measurements were made between carotid-femoral, carotid-radial and femoral-posterior tibial sites, using an ultrasound technique. Coronary artery calcification (CAC) scores were measured by multislice computed tomography. Carotid and femoral intima-media thickness (IMT) and presence of plaque were determined by ultrasound. Known coronary artery disease was confirmed by angiography. Participants were grouped into four categories of CAC score: 0-10, 11-100, 101-400, > 400 Hounsfield Units (HU). Measurements of blood pressure, heart rate and fasting bloods were made in all individuals. RESULTS: Carotid-femoral PWV correlated positively with CAC score and increased with incremental coronary calcification category (median carotid-femoral PWV 16.8 m/s in those with CAC score > 400 HU and 13.8 m/s in those with CAC score < 10 HU; P = 0.003). Carotid-femoral PWV also correlated with carotid and femoral IMT (P < 0.001, P = 0.004, respectively) and with carotid and femoral plaque (P = 0.001, P = 0.038, respectively). Increased carotid-femoral PWV also correlated with increasing age (P < 0.001), systolic blood pressure (P < 0.001), mean arterial pressure and pulse pressure (P < 0.001). Carotid-radial and femoral-posterior tibial PWV were not significantly associated with CAC score, carotid or femoral IMT or carotid plaque. CONCLUSIONS: Carotid-femoral PWV is a better indicator of atherosclerosis than either carotid-radial or femoral-posterior tibial PWV, and should be used preferentially in studies of atherosclerosis and in stratifying risk in clinical settings.     

Asymmetric dimethylarginine is associated with carotid atherosclerosis in patients with essential hypertension

Abstract

This study was to assess the relationship between asymmetric dimethylarginine (ADMA) and carotid atherosclerosis in patients with essential hypertension. A total of 182 individuals with never-treated essential hypertension and 182 age-matched healthy controls were studied. Plasma ADMA levels, mean intima-media thickness (IMT) and plaque score were significantly greater in hypertensive patients than normotensive controls. ADMA was positively correlated with mean IMT. On multiple logistic regression analysis, ADMA was a crucial independent predictor of carotid plaque formation (plaque score ≥1.1). Our results suggest that increased levels of ADMA are associated with the development of carotid atherosclerosis in hypertensive patients.     

Different risk factors for the maximum and the mean carotid intima-media thickness in hemodialysis patients

OBJECTIVE: High-resolution B-mode ultrasonography has been widely used for the noninvasive assessment of atherosclerosis in hemodialysis patients. But, there are two major methods of carotid ultrasonography: one including plaque and the other excluding plaque. METHODS: The subjects were 112 hemodialysis patients (58 men and 54 women) with a mean age of 55.8 +/- 13.0 years. The maximum intima-media thickness (IMT) of the carotid artery (including plaque) was measured as an index of arterial wall thickening and atheroma formation, while the mean IMT (without plaque) was measured as an index of arterial wall thickening. In addition the value of (maximum-mean) IMT was calculated as an index of atheroma formation. Therefore, the independent risk factors associated with the maximum IMT, mean IMT, and (maximum-mean) IMT were investigated by stepwise multiple regression analysis. RESULTS: The independent risk factors associated with the maximum IMT were age, diabetes mellitus, smoking, and intact parathyroid hormone (PTH) (R = 0.569, p < 0.0001), while factors associated with the mean IMT were age, hypertension, dyslipidemia, intact PTH, and lipoprotein (a) (R = 0.602, p < 0.0001). The independent risk factors associated with the (maximum-mean) IMT were age, diabetes mellitus, smoking, and intact PTH (R = 0.515, p < 0.0001). CONCLUSION: These findings suggest that risk factors for the maximum IMT and mean IMT are somewhat different in hemodialysis patients.     

The Relationship between coronary artery calcification as assessed by multi-detector computed tomography and arterial stiffness

Pulse wave analysis and intima-media thickness (IMT) of carotid artery are the non-invasive indicators of subclinical atherosclerosis. Coronary artery calcification (CAC) score measured by multi-detector computed tomography (MDCT) is well known as a predictor of coronary heart disease (CHD). We investigated the association between coronary calcification assessed by MDCT and extracoronary atherosclerosis measured by pulse wave analysis and IMT of carotid artery. Arterial stiffness and carotid IMT were measured consecutively in 133 patients who underwent their first coronary MDCT angiography due to chest pain. Patients were divided into three groups according to the CAC score (group 1, score = 0, n = 62; group 2, 0 < score < 400, n = 58; group 3, score ≥ 400, n = 13). The classification of CAC score was associated with age, prevalence of hypertension and dyslipidemia, systolic blood pressure, pulse pressure, brachial-ankle pulse wave velocity, percentage of brachial mean artery pressure, upstroke time (UT), augmentation index, and carotid IMT. In a multivariate analysis, age (P = .048), hypertension (P = .007), dyslipidemia (P = .24), and mean ankle UT (P = .038) were independent variables for the classification of CAC score. The UT of pulse wave was significantly associated with the CAC score. The increased UT of pulse wave might provide incremental risk prediction in addition to that defined by conventional CHD risk assessment.     

Relationship between mitral annular calcification and severity of carotid atherosclerosis in patients with symptomatic ischemic cerebrovascular disease

OBJECTIVES: Many studies have reported the association between mitral annular calcification (MAC) and stroke. MAC has been speculated to be a direct embolic source of stroke. Recently, the association between MAC and atherosclerosis in the coronary artery, aorta, and carotid artery has been reported. This prospective study investigated the association between MAC and severity of carotid atherosclerosis in patients with symptomatic ischemic cerebral disease to evaluate the association between MAC and atherosclerosis as a cause of stroke. METHODS: We studied 377 patients with ischemic cerebral disease (253 men, 124 women, mean age 68 +/- 11 years) who underwent echocardiography to determine the presence of MAC and carotid ultrasonography to determine the severity of carotid atherosclerosis. Plaque score was the sum of the maximum intimamedia thickness in the common carotid region, the bifurcation bulb region, and the internal carotid artery region, including both right and left arteries. RESULTS: MAC was found in 86 patients, and was more frequent in women, the elderly, and patients with diabetes or hyperlipidemia (p < 0.05). Plaque score was higher in patients with than without MAC (8.3 +/- 5.8 vs 5.2 +/- 5.2 mm, p < 0.001). Multivariate regression analysis identified MAC (r = 0.26, p < 0.0001), female sex (r = -0.12, p = 0.03), and age (r = 0.23, p < 0.0001) as independently associated with plaque score. CONCLUSIONS: MAC is independently associated with severity of carotid atherosclerosis in patients with symptomatic ischemic cerebral disease. This association suggests MAC may be indirectly related to cerebrovascular disease as a marker of the presence of progressive arteriosclerosis for thromboemboli causing stroke.     

Carotid atherosclerosis in chronic renal failure-the central role of increased plaque burden

Studies on carotid artery atherosclerosis have been performed in order to understand the high risk for cardiovascular disease in chronic renal failure (CRF). The purpose of this study was to evaluate the extent and nature of carotid artery atherosclerosis in patients with CRF. Of the 135 patients with CRF (52 +/- 11 years), 58 had moderate to severe predialysis CRF (PR), 36 were on dialysis treatment (DI), and 41 were renal transplant recipients (TR). In addition, 58 control subjects (CO) were examined. Common carotid artery intima-media thickness (IMT), plaque prevalence, plaque score, and stiffness index beta were determined. Furthermore, plaque calcification and internal carotid artery stenoses were classified. Plaque prevalence (PR 64%, DI 61%, TR 51%, CO 28%; P < 0.001) and plaque score (PR 3.3 +/- 4.3, DI 3.0 +/- 3.4, TR 2.5 +/- 3.2, CO 0.8 +/- 1.7 mm; P < 0.001) were significantly greater in the CRF patient groups compared to the controls, whereas no difference in IMT was noted between the study groups. The prevalences of plaque calcification and internal carotid artery stenoses were higher among the CRF patient groups. In addition, the stiffness index beta was higher in the CRF patient groups. The present study shows that the characteristic alterations of the carotid arteries in CRF include increased plaque burden, calcification and increased arterial stiffness.     

Association between hemodynamics in the common carotid artery and severity of carotid atherosclerosis in patients with essential hypertension

BACKGROUND: Carotid intima-media thickness (IMT) and plaque burden evaluated by B-mode ultrasound have been used as relevant indicators for carotid atherosclerosis. This study was aimed to investigate the relationship between hemodynamic parameters in the common carotid artery (CCA) and the severity of carotid atherosclerosis in untreated hypertensive patients. METHODS: Carotid IMT and plaque burden were evaluated in bilateral CCA, bifurcations, external and internal carotid arteries using duplex ultrasound in 80 untreated hypertensive patients. The patients were divided into four groups according to plaque burden. Hemodynamic parameters of CCA, including peak and mean circumferential wall tension (CWT), tensile stress (TS), wall shear stress (WSS), and Young's elastic modulus (YEM), were calculated after measurements of internal diameter (ID), IMT, and peak and mean flow velocities of CCA. Arterial stiffness was also assessed using the brachial-ankle pulse wave velocity (baPWV). RESULTS: Age, pulse pressure, creatinine, carotid IMT, and mean TS were shown to have significant differences among the four plaque groups (P < 0.05). Peak CWT and peak TS were also shown to have marginal differences. In univariate analysis, the peak and mean CWT and TS were significantly correlated with plaque score. Stepwise multiple regression analysis showed that carotid IMT, age, and peak CWT were independently associated with plaque score. CONCLUSIONS: These results suggest that the CWT and TS of the CCA are associated with the severity of carotid atherosclerosis in untreated hypertensive patients. Hence, the hemodynamics of vessels may contribute to the plaque burden of low-resistance arteries.     

The Relationship between Coronary Artery Calcification as Assessed by Multi-Detector Computed Tomography and Arterial Stiffness

Pulse wave analysis and intima-media thickness (IMT) of carotid artery are the non-invasive indicators of subclinical atherosclerosis. Coronary artery calcification (CAC) score measured by multi-detector computed tomography (MDCT) is well known as a predictor of coronary heart disease (CHD). We investigated the association between coronary calcification assessed by MDCT and extracoronary atherosclerosis measured by pulse wave analysis and IMT of carotid artery. Arterial stiffness and carotid IMT were measured consecutively in 133 patients who underwent their first coronary MDCT angiography due to chest pain. Patients were divided into three groups according to the CAC score (group 1, score = 0, n = 62; group 2, 0 < score < 400, n = 58; group 3, score ≥ 400, n = 13). The classification of CAC score was associated with age, prevalence of hypertension and dyslipidemia, systolic blood pressure, pulse pressure, brachial-ankle pulse wave velocity, percentage of brachial mean artery pressure, upstroke time (UT), augmentation index, and carotid IMT. In a multivariate analysis, age (P = .048), hypertension (P = .007), dyslipidemia (P = .24), and mean ankle UT (P = .038) were independent variables for the classification of CAC score. The UT of pulse wave was significantly associated with the CAC score. The increased UT of pulse wave might provide incremental risk prediction in addition to that defined by conventional CHD risk assessment.     

Increased human urotensin II levels are correlated with carotid atherosclerosis in essential hypertension

BACKGROUND: Circulating blood levels of human urotensin II (U-II), the most potent vasoconstrictor peptide identified to date, are increased in patients with essential hypertension. Our previous studies showed that U-II accelerates human macrophage foam cell formation and vascular smooth muscle cell proliferation, suggesting development of atherosclerotic plaque. In this study, we demonstrated a correlation between plasma U-II level and progression of atherosclerosis in hypertensive patients. METHODS: The intima-media thickness (IMT) and plaque score in the carotid artery, blood pressure (BP), plasma levels of U-II, and atherosclerotic parameters were determined in 50 hypertensive patients and 31 normotensive controls. RESULTS: Plasma U-II level, maximum IMT, plaque score, systolic BP, and homeostasis model assessment for insulin resistance (HOMA-IR) were significantly greater in hypertensive patients than normotensive controls. Age, gender, body mass index, and serum levels of high-sensitive C-reactive protein (CRP), HDL and LDL cholesterols, small dense LDL, triglycerides, lipoprotein(a), insulin, and fasting plasma glucose level were not significantly different between the two groups. In all subjects, plasma U-II level showed significant positive correlations with systolic BP, maximum IMT, plaque score, and HOMA-IR. Multiple logistic regression analysis indicated that the contribution of plasma U-II levels to carotid plaque formation (plaque score >/=1.1) was significantly still greater with a 60% increase than those of established risk factors, such as age, systolic BP, high-sensitive CRP, small dense LDL, and HOMA-IR. CONCLUSIONS: Our results suggest that increased levels of U-II may play a crucial role in the development of carotid atherosclerosis in hypertensive patients.     

Plasma hepatocyte growth factor and the relationship between risk factors and carotid atherosclerosis.

Hepatocyte growth factor (HGF) has been shown to have a unique stimulating property on the endothelium as well as an anti-apoptotic action on the endothelium. Through these mechanisms, HGF has been shown to have an anti-atherogenic action in animal models. In atherosclerotic disorders, the circulating level of HGF has been shown to be increased to compensate for its decline in tissue. However, whether increased circulating HGF has any influence on the development of atherosclerosis has not been elucidated. In the present study, the association between plasma HGF concentration and the risk factor-carotid atherosclerosis relationship was evaluated. Three hundred and seventeen community-dwelling subjects participated in the study. The plasma concentration of HGF was determined by enzyme-linked immunosorbent assay (ELISA). The subjects were divided into two groups according to the plasma level of HGF: a low HGF group (n=199, plasma HGF < 150 pg/ml) and a high HGF group (n=118, plasma HGF > or = 150 pg/ml). Risk factors for atherosclerosis were evaluated in each subject. Carotid ultrasonography was performed to measure carotid arterial intima-media thickness (IMT) and the presence of plaque. The association between carotid IMT and risk factors was then evaluated in the two HGF groups. The regression lines between age and carotid IMT were significantly different between the low HGF and high HGF groups (F[1,313]=5.98, p=0.015). The regression lines between systolic blood pressure and carotid IMT were also significantly different between the two HGF groups (F[1,313]=5.17, p=0.024). A general linear model showed that the interaction between age and plasma level of HGF was significantly associated with carotid IMT, suggesting that the plasma level of HGF modifies the age-related increase in carotid IMT. In addition, clustering of risk factors was evaluated in subjects with carotid atherosclerosis. The number of total risk factors in carotid atherosclerosis subjects with high plasma HGF was significantly greater than that in those with low HGF, even though the two groups had a similar magnitude of carotid atherosclerosis. In conclusion, these findings indicate that risk factor-dependent augmentation of carotid atherosclerosis could be influenced by circulating HGF.     

血液透析患者颈总动脉僵硬度与无症状性脑梗死的相关性

目的探讨血液透析患者颈总动脉僵硬度与无症状性脑梗死之间的相关关系。方法选取血液透析患者218例,收集患者的临床资料和生物化学数据。超声血管壁跟踪系统测定颈总动脉硬化参数β作为评价颈总动脉僵硬度的指标。血管超声检测颈动脉内膜中膜厚度。颈动脉粥样硬化斑块指数采用Sutton法计算。结果 Pearson相关分析显示,动脉硬化参数β与年龄、透析时间、内膜中膜厚度和斑块指数显著正相关(P<0.05)。多元逐步回归分析显示,脉压(β=0.501,P<0.001)和年龄(β=0.488,P<0.001)是动脉硬化参数β的独立影响因素,内膜中膜厚度和斑块指数为协同影响因素。合并无症状性脑梗死的患者动脉硬化参数β明显高于未合并无症状性脑梗死患者(P<0.001),而两组患者的平均内膜中膜厚度和斑块指数无明显差异。结论合并动脉粥样硬化的血液透析患者颈总动脉僵硬度增加,颈总动脉僵硬度与血液透析患者并发无症状性脑梗死密切相关。     

The association between coronary calcification assessed by electron beam computed tomography and measures of extracoronary atherosclerosis: the Rotterdam Coronary Calcification Study

OBJECTIVES: The present study was designed to examine the associations of coronary calcification assessed by electron beam computed tomography (CT) with measures of extracoronary atherosclerosis. BACKGROUND: Although measures of extracoronary atherosclerosis have been used to predict coronary events, it is not yet known to what extent those measures reflect coronary atherosclerosis. METHODS: The Rotterdam Coronary Calcification Study is a population-based study in subjects age 55 years and over. Participants of the study underwent an electron beam CT scan. Coronary calcification was quantified according to the Agatston calcium score. Measures of extracoronary atherosclerosis included common carotid intima media thickness (IMT), carotid plaques, ankle-arm index (AAI) and aortic calcification. We used the first 2,013 participants for the present analyses. Age-adjusted geometric mean calcium scores were computed for categories of extracoronary measures using analyses of variance. RESULTS: Graded associations with coronary calcification were found for the carotid and aortic measures. Associations were strongest for carotid plaques and aortic calcification; coronary calcification increased from the lowest category (no plaques) to the highest category 9-fold and 11-fold in men and 10-fold and 20-fold in women, respectively. A nonlinear association was found for AAI with an increase in coronary calcification only at lower levels of AAI. CONCLUSIONS: In this population-based study, graded associations were found between coronary calcification and common carotid IMT, carotid plaques and aortic calcification. A nonlinear association was found between coronary calcification and the AAI.