Arterial wall thickening and stiffening in children and adolescents with type 1 diabetes

OBJECTIVE: We evaluated structural and functional characteristics of the common carotid artery (CCA), a marker of early carotid atherosclerosis, and investigated their relation to metabolic and anthropometric parameters in children and adolescents with type 1 diabetes. MATERIALS AND METHODS: Non-invasive ultrasonographic measurements were made in 45 type 1 diabetic patients and 33 controls. Age, sex, and body mass index were matched between patients and controls. We investigated intima-media thickness (IMT), compliance, distensibility, diastolic wall stress (DWS) and incremental elastic modulus (IEM) of the CCA. Metabolic and anthropometric parameters such as serum lipids, plasma glycated haemoglobin, body mass index, waist-hip ratio and blood pressure were assessed. RESULTS: The diabetic patients had significantly higher CCA-IMT than the controls (0.48+/-0.06mm versus 0.33+/-0.07mm; p<0.001). The diabetic children had significantly higher values than the controls for DWS (1.18+/-0.29mmHgx10(2) versus 0.81+/-0.25mmHgx10(2); p<0.001) and for IEM (1.26+/-0.57mmHgx10(3) versus 0.77+/-0.28mmHgx10(3); p<0.001). The difference was not significant between patients and controls for arterial compliance and for distensibility (p>0.05). In a multivariate regression model for all subjects, diabetic state was the best predictor of IMT (p<0.001), DWS (p<0.001) and IEM (p=0.001). CONCLUSION: Our results suggested that children and adolescent patients with type 1 diabetes are associated with early impairment of CCA structure and function and that diabetic state may be the main risk factor for CCA wall stiffening and thickening, which are of considerable concern as possible early events in the genesis of atheroma.     

Changing associations between progressive cardiovascular autonomic neuropathy and carotid atherosclerosis with increasing duration of type 2 diabetes mellitus

To clarify associations between cardiovascular autonomic neuropathy (CAN) and the progression of carotid artery atherosclerosis in Type 2 diabetic patients, cardiovascular autonomic nerve function was related to carotid artery ultrasound in 61 Type 2 diabetic patients, 5 and 8 years after the diagnosis of diabetes. Between 5 and 8 years after diagnosis, age-adjusted acceleration index (AI) decreased (from -0.306+/-1.034 to -0.702+/-1.072; P=.0139), whereas age-adjusted expiration/inspiration (E/I) ratio was unchanged (-0.583+/-1.038 and -0.828+/-1.028; P=.1164). Intima-media thickness (IMT) increased in both the common carotid artery (CCA; from 0.854+/-0.219 to 0.913+/-0.241 mm; P<.0001) and the carotid bulb (from 1.789+/-0.714 to 2.128+/-0.881 mm; P<.0001), corresponding to a yearly IMT increase of 0.032+/-0.039 mm in the CCA and 0.146+/-0.204 mm in the carotid bulb. This value did not correlate with the AI or E/I ratios. In age-controlled partial correlation in the first examination, AI correlated inversely with mean (r=-.33, P=.018) IMT in the CCA, but not with IMT in the carotid bulb (r=-.14, P=.303). However, in contrast to the first examination, at follow-up, AI correlated inversely with the mean IMT of the carotid bulb (r=-.40, P=.007), lumen diameter of the CCA (r=-.31, P=.034), and plaque score (r=-.29, P=.041), but not with IMT of the CCA (r=-.04, P=.861). There were no correlations between the E/I ratio and carotid variables. In conclusion, CAN was associated with features of carotid atherosclerosis, which, in the carotid bulb, might affect baroreceptor function with the progression of Type 2 diabetes.     

Carotid atherosclerosis is correlated with extent and severity of coronary artery disease evaluated by myocardial perfusion scintigraphy

Increased intima-media thickness (IMT) in the common carotid artery (CCA) correlates with conventional risk factors for cardiovascular disease and is an independent predictor of cardiac events. However, correlation between IMT and degree of ischemic heart disease evaluated by coronary angiogram is weak. The purpose of this study was to investigate the relationship between measures of carotid atherosclerosis and the extent and severity of coronary artery disease (CAD) in 111 consecutive patients (60 men and 51 women, mean age 60 years) with known or suspected CAD who were investigated with adenosine-stress myocardial perfusion scintigraphy. Common carotid artery lumen diameter (LD) and IMT of the carotid bulb and distal CCA were measured with ultrasound, and CCA cross-sectional intima-media area (CIMA) was calculated. Seventy-two of 110 patients (65%) had significant perfusion defects. Increasing carotid plaque occurrence (absence, unilateral or bilateral occurrence) correlated with more advanced CAD (p<0.01). The extent and severity of myocardial hypoperfusion correlated significantly with presence of carotid plaque (r=0.23 and 0.24 respectively, p<0.05), CIMA (r=0.23 and 0.22, p<0.05), and LD (r<0.26 and 0.25, p<0.01) but not with IMT. In contrast to CIMA, LD failed to show an independent relation to extent of CAD after adjustment for age, sex, and body mass index. In conclusion, in subjects with intermediate to high risk of ischemic heart disease, occurrence of carotid plaques and increased cross-sectional intimamedia area in the common carotid artery are the best parameters for predicting CAD expressed as myocardial hypoperfusion.     

Association of carotid hemodynamics with risk of coronary heart disease in a Taiwanese population with essential hypertension

BACKGROUND: The resistive index (RI) of the carotid artery is a hemodynamic parameter that depends on the degree of vascular resistance in hypertensive patients. The pulsatility index (PI) of the carotid artery was shown to be associated with microangiopathy in diabetic patients. In contrast to carotid intima-media thickness (IMT), no study has yet applied the carotid RI and PI to estimate coronary heart disease (CHD) risk. METHODS: Framingham risk scores (FRS) were determined for 62 patients (32 women; mean age 65 years (range 35-83)) with essential hypertension. Duplex sonography of the common carotid artery (CCA) was performed, with determination of RI, PI, and IMT. RESULTS: The mean FRS of all patients was 14.3% (range 1-30%), the mean IMT value of CCA was 0.89 +/- 0.23 mm, the mean RI was 0.71 +/- 0.07, and the mean PI was 1.46 +/- 0.39. FRS was found to have highly significant correlations with RI and PI (r = 0.47, P < 0.001 and r = 0.45, P < 0.001, respectively). The correlation between FRS and IMT was also significant (r = 0.41, P = 0.001). Multiple stepwise regression analysis showed that RI was an independent determinant of the risk of CHD. CONCLUSIONS: Although RI indirectly reflected the atherosclerotic process, the correlation between RI and CHD risk was comparable to the well-known correlation between cardiovascular event and carotid IMT. Hence, carotid RI can be used as a tool for risk stratification in Taiwanese patients with essential hypertension.     

Decrease in carotid intima-media thickness in hypothyroid patients after normalization of thyroid function

OBJECTIVE: This case-control study was carried out to assess whether levothyroxine (L-T4) replacement might cause regression of the enhanced atherosclerosis seen in hypothyroid patients. PATIENTS AND METHODS: Intima-media thickness (IMT) in the common carotid artery (CCA) was measured from digitalized still images taken during scanning by high-resolution ultrasonography as an indicator of early atherosclerosis. Thirty-five hypothyroid patients were examined for their CCA IMT before and 1 year after normalization of thyroid function by L-T4 replacement. As control, 35 healthy subjects were enrolled from among the participants in a local health-check programme conducted at the Osaka City University Hospital. RESULTS: Basal CCA IMT was significantly higher in hypothyroid patients [0.635 +/- 0.018 (mean +/- SE) mm] than in control subjects (0.559 +/- 0.021 mm, P < 0.005). After 1 year of euthyroidism, 34 out of 35 patients showed a significant decrease of CCA IMT, to 0.552 +/- 0.015 mm (P < 0.0001), a level comparable to normal controls. CCA IMT change was closely associated with basal levels of total cholesterol (r = -0.472, P= 0.0031), low-density lipoprotein (LDL) cholesterol (r = -0.441, P= 0.0076) and the total/HDL cholesterol ratio (r =-0.435, P= 0.0057), but not with any of the other variables measured except for age (r = -0.353, P= 0.0296). CONCLUSIONS: This study demonstrated that L-T4 treatment might have the potential to reverse the progression of atherosclerosis in hypothyroid patients. Furthermore, it suggests that increased levels of LDL cholesterol and the total/HDL cholesterol ratio have an important role in the increased common carotid intima-media thickness in hypothyroid patients.     

Low insulin sensitivity measured by both quantitative insulin sensitivity check index and homeostasis model assessment method as a risk factor of increased intima-media thickness of the carotid artery

The present study evaluated the association of ultrasonographic manifestations of carotid atherosclerosis with glucose status, various components of the insulin resistance syndrome, and insulin sensitivity measured by a novel quantitative insulin sensitivity check index (QUICKI = 1/[log(I0) + log (G0)]). Carotid ultrasonographic measurements were performed on 54 diabetic subjects, 97 subjects with impaired glucose tolerance and 57 normoglycemic subjects. QUICKI and insulin resistance measured by a HOMA (homeostasis model assessment) method had a high negative correlation (r = -0.995, P < 0.001). QUICKI was lower in diabetic subjects (0.319 +/- 0.022) than in subjects with impaired glucose tolerance (0.334 +/- 0.027) or normoglycemia (0.335 +/- 0.022, P = 0.002). There was an increasing trend in the mean and maximal intima-media thickness (IMT) of the common carotid artery (CCA) with worsening of glucose status. The maximal IMT of the CCA correlated inversely with QUICKI (r = -0.158, P = 0.027). The prevalence of severe CCA atherosclerosis (maximal IMT of the CCA > or = 1.2 mm) was 41% in men and 16% in women (P < 0.001). It was also associated with a long (> or =26 yr) smoking history. The prevalence of severe CCA atherosclerosis was 11% in the highest QUICKI tertile, 36% in the middle tertile, and 33% in the lowest tertile (P = 0.002). Systolic blood pressure was higher and high-density lipoprotein cholesterol lower in subjects with severe CCA atherosclerosis, compared with those without it. In multiple regression analysis, the adjusted odds ratio for severe CCA atherosclerosis was 5.7 (95% confidence interval, 2.2-15.1) in subjects in the two lowest tertiles of QUICKI, compared with those in the highest tertile.     

Dissociation between microalbuminuria and common carotid thickness in essential hypertensive men

BACKGROUND: The reasons why microalbuminuria (albuminuria > or = 15 microg/min), an expression of a renal microcirculatory abnormality, predicts cardiovascular disease in essential hypertension are unsettled. To test the hypothesis that microalbuminuria represents a marker of subclinical atherosclerosis, we evaluated its association with common carotid artery (CCA) intima media thickness (IMT), a measure of preclinical atherosclerosis and an independent predictor of cardiac and cerebrovascular events, in uncomplicated essential hypertensive individuals. MATERIALS AND METHODS: Albuminuria, ultrasonographic CCA IMT (the mean of six bilateral far wall measurements within 1.5 cm proximally to the flow divider), brachial blood pressure (BP), smoking habits and lipids were evaluated in 136 stage 1-3 untreated essential hypertensive men free of cardiovascular disease. RESULTS: CCA IMT did not differ between normo- (n = 99) and microalbuminuric (n = 37) patients. The correlation between CCA IMT and albuminuria was not significant, and the prevalence of microalbuminuria across IMT quartiles was not different. Microalbuminuric patients showed higher systolic BP and that parameter was the only independent correlate in a multivariate logistic regression model including also age, CCA IMT, diastolic BP, lipids and smoking habits as independent variables and microalbuminuria as the dependent one. CONCLUSION: This cross-sectional study in hypertensive subjects free of cardiovascular disease has shown a dissociation between microalbuminuria and CCA IMT, a surrogate measure of subclinical atherosclerosis, and a parameter linearly related to cardiovascular events. The data do not support the theory of microalbuminuria as a surrogate measure of subclinical atherosclerosis, while confirming the importance of systolic BP levels as an independent correlate of increased albuminuria in essential hypertension. Journal of Human Hypertension (2000) 14, 831-835     

The correlation of common carotid arterial diameter with atherosclerosis and diabetic retinopathy in patients with type 2 diabetes mellitus

The clinical significance of the diameter of the common carotid artery (CCA) measured ultrasonographically in diabetic practice has not been sufficiently established. The objective of this study was to investigate the relationship of the ultrasonic CCA diameter with atherosclerotic measures and diabetic retinopathy as a microvascular complication in patients with type 2 diabetes mellitus (T2DM). This hospital-based cross-sectional study included 102 patients with T2DM (men: 65%, mean age: 57 years) who had no apparent carotid arterial stenosis and no history of cardiovascular or severe renal disease. The current smoking status, body mass index, blood pressure, hemoglobin A1c, serum low-density lipoprotein cholesterol, and ultrasonic measures of carotid arteries (CCA diameter, intima-media thickness (IMT), plaque score) were measured. The cardio-ankle vascular index (CAVI) and the presence of diabetic retinopathy were also assessed. The CCA diameter showed a significant positive correlation with the mean IMT or plaque score. The CAVI had a significant positive correlation with the mean IMT, plaque score, and CCA diameter, while diabetic retinopathy had a significant positive correlation with the CCA diameter, but not the mean IMT or plaque score. These results were unaltered after adjusting for multiple confounders. The CCA diameter may serve as a useful marker for atherosclerosis and diabetic retinopathy, and in particular, may be a marker associated with diabetic retinopathy more clearly than the carotid IMT and plaque score, in patients with T2DM.     

Subclinical atherosclerosis in rheumatoid arthritis in India

OBJECTIVE: Patients with rheumatoid arthritis (RA) have high cardiovascular morbidity and mortality as compared to the general population. Indians are also at increased risk of developing early and severe atherosclerotic coronary artery disease. Carotid intima-media thickness as measured by ultrasound is a validated surrogate marker of atherosclerosis. We studied the prevalence of subclinical atherosclerosis in Indian patients with RA. METHODS: Common carotid IMT (CCA IMT) was measured at the level of carotid bifurcation along with fasting lipid profile in 57 RA patients and 45 age and sex matched controls. Values of mean CCA IMT above mean + 2 SD of the control group were defined as abnormal IMT. Variables of disease activity and severity were measured in RA patients. Patients and controls with known traditional cardiovascular risk factors were excluded from the study. Student t test and chi-square test for proportion were used for statistical analysis. A logistic regression analysis was done to find out independent predictors of abnormal IMT. RESULTS: Nineteen RA patients (33.3%) and 2 controls (4.44%) had abnormal IMT values. RA patients had significantly increased mean CCA IMT (0.558 +/- 0.137 mm) as compared to controls (0.416 +/- 0.002 mm; p < 0.0001). Age > or = 42 years, duration of disease > or= 6 years, and tender joint count > or = 5 predicted increased risk of having abnormal CCA IMT in a logistic regression analysis. CONCLUSION: One-third of Indian RA patients had subclinical atherosclerosis. Age and tender joint count were independent predictors of abnormal CCA IMT.     

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.     

Ankle-arm blood pressure index as a correlate of preclinical carotid atherosclerosis in elderly Japanese men

Peripheral artery disease correlates with preclinical carotid atherosclerosis in Western populations. However, little is known about this correlation in Asian populations. In a cross-sectional population-based study, we examined the correlation between peripheral arterial disease and carotid intima-media thickness (IMT) among 726 Japanese men aged 60-79 years. None of them had a history of clinical peripheral arterial disease. The ankle-to-arm systolic blood pressure index (AAI) was used as a surrogate estimate of peripheral arterial disease. Compared to men with AAI> or =0.90, those with AAI<0.90 were 1-4 years older, and had lower mean body mass index and higher prevalence of current smokers. The mean AAI correlated inversely and linearly with maximum IMT in the common and internal carotid arteries (CCA and ICA), and men with AAI<0.90 had higher prevalence of maximum ICA IMT > or =1.5mm than did those with AAI> or =0.90. The multivariate odds ratio (95% confidence interval) of maximum ICA IMT > or =1.5mm was 2.9 (1.0-8.4), while that of maximum CCA IMT> or =1.1mm was 1.4 (0.5-3.8) for men with AAI<0.90 versus > or =1.30. The sensitivity was 65% and the specificity was 98% for low AAI to detect ICA IMT > or =1.5mm. Low AAI is a strong correlate for internal carotid atherosclerosis and the AAI measurement may be of use to screen for preclinical peripheral atherosclerosis among Japanese elderly men.     

Determinants of early carotid atherosclerosis progression in young patients with type 1 diabetes mellitus.

The results of cross-sectional studies addressing early preintrusive atherosclerosis in type 1 diabetic patients are conflicting. In an observational longitudinal study we determined the course of carotid artery intima-media thickness (IMT) over a period of 2.5 years in mean. A total of 102 patients with type 1 diabetes mellitus (age < or = 40 years, diabetes duration > or = 2 years at baseline examination) who were participants of the baseline examination was studied again in a follow-up. HbA1c, albumin excretion rate (AER), lipids, systolic and diastolic blood pressure, retinopathy, and current smoking status were assessed at baseline and follow-up. The IMT of the common carotid artery was measured by high-resolution ultrasound, the maximum IMT was evaluated. The annual progression rate (APR) was calculated from the difference between baseline and follow-up IMT reading and the time between both examinations. The follow-up IMT was significantly higher, compared to the baseline measurement: 0.65 +/- 0.18 vs. 0.57 +/- 0.14 mm (p < 0.001), the mean APR was 0.033 mm/year. The APR was correlated with age (r = 0.337, p < 0.01), diabetes duration (r = 0.252, p < 0.05), hypertension (r = 0.225, p < 0.05), and systolic blood pressure (r = 0.281, p < 0.05) at the baseline examination. Comparing subgroups, defined according to APR tertiles, with no IMT progression (first tertile, mean APR - 0.012 mm/year), mild progression (second tertile, mean APR 0.037 mm/year), and advanced progression (third tertile, mean APR 0.088 mm/year), patients with advanced progression significantly (p < 0.05) more often had hypertension and nephropathy than subjects with mild progression. In a multiple linear regression analysis, the changes of plaque frequency and of the nephropathy status between baseline and follow-up examinations were independent predictors of the APR.     

Vascular function and carotid intimal-medial thickness in children with insulin-dependent diabetes mellitus

OBJECTIVES: The objective of this study was to evaluate endothelium-dependent vasodilation and carotid intimal-medial thickness (IMT) in children with insulin-dependent diabetes mellitus. BACKGROUND: Diabetes mellitus is an established risk factor for atherosclerosis. Vascular complications of diabetes are not clinically evident in diabetic children. However, preclinical atherosclerosis is more common in young subjects exposed to cardiovascular risk factors. Endothelial function and carotid IMT, known to be abnormal in preclinical atherosclerosis, have not been studied concurrently in a pediatric population exposed to a risk factor for atherosclerosis. METHODS: We studied 31 diabetic teenagers (age 15.0 +/- 2.4 years; duration of diabetes 6.8 +/- 3.9 years) and 35 age-matched healthy children (age 15.7 +/- 2.7 years). Using high-resolution vascular ultrasound, we compared carotid IMT and brachial artery responses to reactive hyperemia (endothelium-dependent vasodilation) and to sublingual nitroglycerin (endothelium-independent vasodilation). RESULTS: There was no difference in baseline brachial artery diameter between the two groups. Endothelium-dependent vasodilation was significantly lower in diabetic children compared with healthy children (4.2 +/- 3.8% vs. 8.2 +/- 4.2%, p < 0.001). There was no difference in endothelium-independent vasodilation (17 +/- 6% vs. 18 +/- 6%, p = NS) or mean carotid IMT between the groups (0.33 +/- 0.05 vs. 0.32 +/- 0.08 mm, p = NS). Endothelium-dependent brachial vasodilation correlated with blood glucose levels (r = 0.58, p = 0.001) and was weakly and inversely related to the duration of diabetes (r = -0.4, p = 0.02), total cholesterol, and low-density lipoprotein cholesterol levels. CONCLUSIONS: Endothelial function is impaired in children with diabetes mellitus within the first decade of its onset and precedes an increase in carotid IMT. The relative timing of these events is important in the evaluation of strategies to prevent progression of atherosclerosis and other vascular complications in this patient population.     

Carotid atherosclerosis,intima media thickness and risk factors--an analysis of 1781 asymptomatic subjects in Taiwan

The aim of this study was to investigate the association of intima media thickness (IMT) and plaque with risk factors for atherosclerosis in asymptomatic subjects in Taiwan. Between 1998 and 2001, the study recruited 1781 asymptomatic subjects (1131 men and 650 women [mean age, 49 years; range 18-85 years]). These were examined by B-mode ultrasound to measure the IMT at the far wall of the common carotid artery (CCA) and the extent of plaque formation. A wide range of vascular risk factors including age, gender, smoking, body mass index, blood chemistry, and previous history were surveyed. The mean (+/-S.D.) IMT observed was 0.68 (+/-0.12) and 0.66 (+/-0.11) mm for men and women, respectively, (P=0.0008). The mean (S.D.) IMT of the CCA was 0.66 (+/-0.12) mm on the right side and 0.68 (+/-0.12) mm on the left side (P=0.0004). IMT increased with aging, according to the equation IMT=(0.005xage in years)+0.403 [corrected]. Higher IMT was associated with male gender, and IMT was greater in the left CCA. About 36.9% of subjects had carotid plaques. The percentage of plaque increased with aging. The plaque prevalence was positively associated with IMT. The value of IMT over the cut point of 0.68 mm correlated with obviously increased risk of carotid atherosclerosis. Age, systolic blood pressure and fasting blood sugar were independent risk factors related to both carotid atherosclerosis and thick IMT.     

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.     

Correlations between plasma homocysteine and folate concentrations and carotid atherosclerosis in high-risk individuals: baseline data from the Homocysteine and Atherosclerosis Reduction Trial (HART)

Homocysteine has been proposed as a risk factor for atherosclerosis. The association between plasma total homocysteine (tHcy) concentration and carotid atherosclerosis has not been thoroughly studied in high-risk populations with vascular disease. For this study, carotid atherosclerosis was assessed by measurements of carotid intima-media thickness (IMT) and plaque calcification in 923 patients with vascular disease or diabetes. Associations with tHcy and plasma folate concentrations were examined. The mean and single maximum carotid IMT were 1.27 +/- 0.34 mm and 2.41 +/- 0.83 mm, respectively. The mean segment plaque calcification score was 27.8%. tHcy correlated with mean (r = 0.13; p < 0.001) and single maximum (r = 0.12; p < 0.001) carotid IMT. There was a progressive increase in mean and single maximum carotid IMT across quartiles of tHcy (p < 0.0001 for trend). These associations were no longer significant after adjusting for other CV risk factors. A trend towards an inverse association between plasma folate and mean max carotid IMT was found in both univariate and multivariable analyses. However, the plaque calcification score increased across quartiles of tHcy (p < 0.01) and decreased across quartiles of plasma folate concentrations (p < 0.05) after multiple adjustments. In conclusion, in high-risk individuals, tHcy and low folate concentrations were only weakly associated with carotid IMT. In contrast, we found an independent association with the plaque calcification score, a measure of more advanced atherosclerosis. The effect of tHcy lowering on carotid atherosclerosis and stroke prevention warrants further investigation.     

Mean HbA1c over 18 years predicts carotid intima media thickness in women with type 1 diabetes

Aims/hypothesis Intima media thickness (IMT) of the common carotid artery (CCA) is a validated surrogate marker of early atherosclerosis. The aim of our study was to assess the association between IMT in CCA and long-term mean HbA₁c in type 1 diabetes. We also elucidated the association between carotid IMT and preclinical coronary atherosclerosis.Methods In 39 individuals with type 1 diabetes, HbA₁c was measured prospectively over 18 years. The IMT examinations were performed with high-resolution ultrasound. The association between carotid IMT and preclinical coronary atherosclerosis (assessed by intravascular ultrasound [IVUS]) was tested in 29 of the patients.Results Mean HbA₁c over 18 years was 8.2% (range: 6.6–11.3%). Mean age at follow-up after 18 years was 43 years and mean duration of diabetes was 30 years. IMT was significantly higher in diabetic patients than in an age- and sex-matched reference population. The IMT values were at the same level as for controls who were 20 years older. In women, HbA₁c was significantly associated with mean average CCA IMT (r²=0.77, p<0.0001 when adjusted for age), whereas there was no significant association for men. Among women, a significant association was also found between carotid IMT and the percentage of coronary vessel area stenosis (r=0.65, p=0.03).Conclusions/interpretation The present findings suggest an important role of long-term hyperglycaemia in the development of atherosclerosis, especially in women with type 1 diabetes.Type 1 diabetes patients have earlier development of, and more advanced, atherosclerosis compared with an age- and sex-matched reference population. In women, carotid IMT reflects preclinical coronary atherosclerosis.     

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.     

Ultrasonographically assessed carotid atherosclerosis in Japanese type 2 diabetic patients: Role of nonesterified fatty acids

The aim of the present study was to evaluate the association of carotid atherosclerosis (intimal-medial thickness [IMT] in plaque-free segments and carotid stenosis in plaque segments) with serum nonesterified fatty acids (NEFA) in diabetic and nondiabetic patients. Fifty-one nonobese nonhypertensive Japanese type 2 diabetic patients aged 38 to 83 years (60.0 +/- 1.5 years, mean +/- SEM) and 23 age-matched (60.4 +/- 2.2 years, P =.439; range, 36 to 74 years) and sex-matched nondiabetic subjects were examined. The duration of diabetes was 9.6 +/- 1.0 years. Body mass index (BMI), blood pressure (systolic pressure, diastolic pressure), glycosylated hemoglobin (HbA(1c)), and fasting concentrations of plasma glucose, serum lipids (triglycerides, total, and high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol) and serum NEFA were measured. Using high-resolution B-mode ultrasound scan, we measured IMT in plaque-free segments of bilateral common carotid arteries, and the mean of IMT in 2 vessels was used for the analysis. Furthermore, we calculated the degree of stenosis in plaque segments of bilateral common carotid arteries. The degree of carotid stenosis was expressed as a percentage ratio between the area of plaque and that of the lumen using the formula (Lumen Area - Residual Lumen) x 100. Both the areas were automatically measured by the system on a frozen transverse scanning plane at the site of maximal narrowing. When 2 or more plaques were present in the vessel, only that causing the greatest degree of stenosis was considered for analysis. Univariate regression analyses showed that mean IMT in plaque-free segments was positively correlated with age (r =.498, P =.0004) and NEFA (r =.354, P =.0188) in type 2 diabetic patients. The degree of stenosis was positively correlated to age (r =.422, P =.0028), duration of diabetes (r =.313, P =.0268) and NEFA (r =.540, P =.0003) in diabetic patients. Other variables, including BMI and lipid profile, were not associated both with mean IMT in plaque-free segments and the degree of stenosis in plaque segments in our diabetic patients. Multiple regression analyses showed that mean IMT in plaque-free segments was independently associated with age (P =.0003, F = 15.2), which explained 26.1% of the variability of IMT in our diabetic patients. The degree of stenosis was independently predicted by NEFA (P =.0047, F = 8.9), which explained 17.2% of the variability of the carotid stenosis in our diabetic patients. In contrast, mean IMT in plaque-free segments was positively correlated to age in nondiabetic subjects (r =.450, P =.0347). There was, however, no relationship between the degree of stenosis and the variables, including age and NEFA, in nondiabetic subjects. These results indicate that the factors contributing to IMT in plaque-free segments and the degree of carotid stenosis in plaque segments are different in nonobese nonhypertensive Japanese type 2 diabetic patients. IMT in plaque-free segments was independently associated with age both in nondiabetic and diabetic subjects, whereas the serum NEFA level independently predicted the degree of stenosis in plaque segments in our diabetic patients, while not in nondiabetic subjects. Thus, NEFA is considered to be one of the new risk factors responsible for the progression of carotid atherosclerosis in nonobese nonhypertensive Japanese type 2 diabetic patients.     

Interrelation between the extent of atherosclerosis in the thoracic aorta, carotid intima-media thickness and the extent of coronary artery disease

Intima-media thickness (IMT) of the common carotid artery and atherosclerosis of the thoracic aorta have been shown to correlate with coronary artery disease (CAD). This study compares the relation between wall changes in the thoracic aorta and the carotid arteries and the angiographic severity and extent of atherosclerotic lesions in the coronary arteries in patients with verified CAD. Atherosclerotic wall changes in the carotid arteries and the thoracic aorta were measured by B-mode ultrasonography and transesophageal echocardiography (TEE), respectively, in 37 subjects aged 65+/-10 years with angiographically verified CAD. The mean value of the common carotid IMT of the right and left sides was 0.87+/-0.21 mm. All subjects had carotid plaques. TEE detected grades II-IV atherosclerotic plaques in the thoracic aorta in 32 of the 37 (86%) patients. A significant correlation was seen between the extent of coronary artery stenosis and aortic plaques score (r=0.46, p=0.008). Mean carotid IMT was also significantly correlated with coronary artery stenosis extent score (r=0.44, p=0.007). Moreover, a significant correlation was seen between the aortic plaque score and the mean carotid IMT (r=0.39, p=0.02). In conclusion, we found a clear and significant relationship between wall changes in the thoracic aorta, common carotid IMT and the angiographic extent of coronary artery stenosis in patients with severe CAD. These findings indicate a potential of B-mode ultrasonography of the carotid arteries and transesophageal echocardiographic aortic examination in the diagnostic and prognostic evaluation of patients with suspected CAD.