Endothelium-dependent vasodilation and carotid artery wall remodeling in athletes and sedentary subjects

In this study, the relationship between age, carotid artery remodeling, and endothelium-dependent vasodilation is investigated in sedentary subjects and athletes. Thirty-two young and old healthy sedentary subjects and 32 age-matched endurance athletes underwent ultrasonography of the carotid wall for measuring intima-media thickness (IMT) and corrected integrated backscatter (C-IBS), two early indicators of the atherosclerosis process. Endothelium-dependent vasodilation was assessed by intra-brachial acetylcholine (strain-gauge plethysmography), at baseline and during NO sythase inhibitor NG-monomethyl-L-arginine (L-NMMA), and the antioxidant Vitamin C. Response to sodium nitroprusside (SNP) was also evaluated. Independently of trained status, IMT and C-IBS were higher in older than in young individuals (p<0.0001), while response to acetylcholine, but not to SNP, was lower (p<0.0001). Older athletes showed lower IMT, lower C-IBS (p<0.0001), greater response to acetylcholine (p<0.0001), and greater inhibition of acetylcholine by L-NMMA (p<0.001) than older controls. Only in older sedentary individuals, Vitamin C increased response to acetylcholine (p<0.001) and restored the inhibiting effect of L-NMMA (p<0.01). In the whole population maximal acetylcholine-induced vasodilation was inversely related to IMT (r=-0.60, p<0.0001) and to C-IBS (r=-0.56, p<0.0001). In conclusion, regular physical training can attenuate the age-related impairment of endothelium-dependent vasodilation, which is related to an attenuation of the age-induced remodeling of the carotid wall.     

Clinical implications of ultrasonic tissue characterization for atherosclerotic carotid intima-media

Current imaging modalities, such as ultrasonic tissue characterization, have enabled accurate determination of the composition of atherosclerotic plaque of excised aortic tissue. The aim of this study is to compare integrated backscatter (IBS) echo signals of the intima-media complex of human carotid arteries between young and elderly subjects, and to evaluate the ability of ultrasonic tissue characterization. We compared the difference in ultrasonic parameters between the carotid arteries of young healthy subjects (n = 27, 25 +/- 1 y.o.) and elderly subjects (n = 55, 75 +/- 4 y.o.). Intima-media thickness (IMT) and calibrated IBS value (C-IBS: Tissue IBS-vessel lumen IBS value) were measured. The IMT values of young and elderly subjects were 0.54 +/- 0.03 and 1.08 +/- 0.07 mm, respectively (p < 0.01). C-IBS of elderly subjects (11.7 +/- 0.8 dB) was significantly higher than that of young subjects (6.9 +/- 0.7 dB). Significantly wider standard deviation of C-IBS value in each individual was observed in elderly subjects (mean +/- SE of individual standard deviation in C-IBS: 4.2 +/- 0.9 dB) compared with that in young subjects (1.7 +/- 0.3 dB). This might reflect varied composition of atherosclerotic plaques in elderly subjects. IBS analysis would become a promising method to distinguish plaque composition quantitatively and to assess the stability of plaques in clinical setting.     

Carotid vascular remodeling in patients with pheochromocytoma

CONTEXT: The influence of catecholamines on vascular remodeling in humans was investigated. OBJECTIVE: The objective was to study the carotid vascular wall in patients with pheochromocytoma (PHEO). DESIGN AND SETTING: An observational study was conducted in a university referral center for blood pressure diseases. PATIENTS: Fourteen patients with PHEO, 15 matched high-normal essential hypertensives, 15 mild essential hypertensives, and 15 controls underwent two-dimensional conventional ultrasonography and ultrasonic tissue characterization of the carotid wall. MAIN OUTCOME MEASURES: Intimal media thickness (IMT), diameter, and corrected ultrasonic integrated backscatter signal (C-IBS) of carotid arteries were evaluated. RESULTS: IMT in PHEOs (0.844 +/- 0.18 mm, mean +/- sd) was greater than not only controls (0.596 +/- 0.09 mm, P < 0.0002) but also high-normal (0.710 +/- 0.17 mm, P < 0.03), and even mild (0.727 +/- 0.20 mm, P = 0.06) hypertensives. IMT in the latter was higher than in controls (P < 0.03), without difference in comparison with high-normal hypertensives. C-IBS values in PHEOs (-21.71 +/- 2.0 dB, mean +/- sd) were greater than in controls (-26.20 +/- 1.73 dB, P < 0.0001) but also than in high-normal (-23.84 +/- 1.16 dB, P < 0.002) and mild (-23.37 +/- 1.99 dB, P < 0.01) hypertensives. C-IBS values in controls were lower than in high-normal (P < 0.0005) and mild (P < 0.0001) hypertensives. Carotid diameter was not significantly different in the four groups. In PHEOs, C-IBS was associated with urinary noradrenaline (r = 0.640, P < 0.01) and normethanephrine (r = 0.737, P < 0.009). CONCLUSIONS: Carotid IMT of PHEOs is higher than in controls and matched groups of hypertensives with comparable or even higher blood pressure. This vascular rearrangement is characterized by increased IBS values due to collagen deposition and vascular fibrosis. Therefore, our data show that abnormal catecholamine levels take part per se in carotid wall remodeling of patients with PHEO.     

Effect of age and sex on carotid intima-media thickness, elasticity and brachial endothelial function in healthy adults: the cardiovascular risk in Young Finns Study.

AIMS: The objective was to produce reference values and to analyse the associations of age and sex with carotid intima-media thickness (IMT), carotid compliance (CAC), and brachial flow-mediated dilatation (FMD) in young healthy adults. METHODS AND RESULTS: We measured IMT, CAC, and FMD with ultrasound in 2265 subjects aged 24-39 years. The mean values (mean +/- SD) in men and women were 0.592 +/- 0.10 vs. 0.572 +/- 0.08 mm (P < 0.0001) for IMT, 2.00 +/- 0.66 vs. 2.31 +/- 0.77%/10 mmHg (P < 0.0001) for CAC, and 6.95 +/- 4.00 vs. 8.83 +/- 4.56% (P < 0.0001) for FMD. The sex differences in IMT [95% confidence interval (CI) for sex difference -0.013 to 0.004 mm, P = 0.37] and CAC (-0.01 to 0.18%/10 mmHg, P = 0.09) became non-significant after adjustments with risk factors and carotid diameter. In FMD, the sex difference was unaltered after adjustments for risk factors, but was reversed after adjustment with brachial diameter (95% CI 0.18-1.32%, P < 0.01). With aging, IMT increased 5.7 +/- 0.4 microm/year and CAC decreased 0.042 +/- 0.003%/10 mmHg/year. The association of age with IMT and CAC was slightly attenuated (12 and 22%, respectively) after adjustments with risk factors, but remained significant (both P < 0.0001). Aging was not significantly related to brachial FMD (P = 0.16). CONCLUSION: Reference values produced in the present study can be utilized in the cardiovascular risk stratification among young people. Sex differences in the markers of subclinical atherosclerosis were mostly explained by differences in risk factors and vessel size. This emphasizes the importance of risk factor control in the prevention of atherosclerosis in young adults.     

Habitual aerobic exercise is associated with smaller femoral artery intima-media thickness with age in healthy men and women.

BACKGROUND: Femoral artery intima-media thickness (IMT), an independent predictor of atherosclerotic disease risk, increases with age in sedentary adults. It is not known whether regular aerobic exercise modulates femoral IMT with ageing. METHODS AND RESULTS: Study 1: Femoral IMT was measured in 173 sedentary, moderately active, and endurance-trained young (20-39 years), middle-aged (40-59 years) and older (60-79 years) men. IMT increased with age in all activity groups (P<0.001). However, IMT was 20-27% smaller in age-matched, endurance-trained compared with sedentary men (P<0.001), and the age-associated increase in IMT was 33% smaller in endurance-trained compared with sedentary men (+0.32 versus +0.45 mm). There was a trend for the IMT to be smaller in moderately active compared with sedentary older men, and the age-associated increase in IMT was 37% smaller in moderately active than sedentary men (+0.28 mm). Study 2: Among 74 premenopausal and postmenopausal sedentary or endurance-trained women, IMT was higher (P<0.001) in postmenopausal compared with premenopausal women regardless of activity status. However, IMT was 15% smaller in endurance-trained compared with sedentary postmenopausal women (P<0.001), and the premenopausal to postmenopausal difference in IMT was approximately 45% smaller in endurance-trained compared with sedentary women (+0.13 versus +0.23 mm). CONCLUSIONS: Femoral IMT increases with age even in habitually exercising adults. However, the age-associated increase and absolute level of IMT are smaller in middle-aged and older adults who perform regular aerobic-endurance exercise, and may contribute to their lower incidence of atherosclerotic disease.     

Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndrome.

BACKGROUND & AIMS: 5-hydroxytryptamine-3 (5-HT 3 ) receptor antagonists improve symptoms in patients with diarrhea-predominant irritable bowel syndrome (D-IBS), 5-HT 4 agonists help those with constipation-predominant IBS (C-IBS). These data suggest excess or deficiency in 5-HT in D-IBS or C-IBS, respectively. Mucosal 5-HT-containing enterochromaffin cells (EC) are increased in postinfectious IBS (PI-IBS). Our aim was to define the postprandial release of 5-HT in PI-IBS and C-IBS patients and to relate this to mucosal 5-HT turnover. METHODS: Fifteen PI-IBS patients with diarrhea-predominant symptoms, 15 C-IBS patients, and 15 healthy controls underwent serial (platelet-poor) plasma 5-HT measurement for 3 hours after a standard 520-kcal meal. Rectal biopsy specimens were assayed for 5-HT and its metabolite 5-hydroxindoleacetic acid (5-HIAA). Colonic transit was measured using radio-opaque markers. RESULTS: Colonic transit was prolonged in C-IBS patients (mean +/- SEM) (49.4 +/- 3.8 h) compared with PI-IBS (26.7 +/- 4.5) and control patients (34.1 +/- 4.5) ( P < .02). Release of 5-HT assessed by area under the curve (AUC) of platelet-poor plasma 5-HT from 0 to 180 minutes postprandially was significantly lower in C-IBS patients (2593 +/- 309 mmol/L . min) compared with P-IBS (5623 +/- 721) and control patients (4822 +/- 598) ( P < .001). PI-IBS patients showed significantly higher peak postprandial plasma 5-HT values (median, range) (71.7, 43.4-125.3) ng/L compared with C-IBS patients (31.2, 15.2-40.5) and control patients (43.6, 26.7-50.1) ( P < .01). Mucosal 5-HT turnover as assessed by mucosal 5-HIAA/5-HT ratio was decreased in both C-IBS and PI-IBS patients, .14 (.01-.6) and .21 (.02-2.5), respectively, compared with control patients 1.12 (.17-3.1) ( P < .002). CONCLUSIONS: C-IBS patients show impaired postprandial 5-HT release whereas PI-IBS patients have higher peak levels, abnormalities that may be related to their different symptoms.     

Kidney function and thickness of carotid intima-media complex in patients with treated arterial hypertension

The aim of the study was to evaluate of the association between renal function and the intima-media thickness of common carotid artery (CCA-IMT) in treated hypertensive patients. Eighty-seven hypertensives (51.7% diabetic), aged >45 years, were examined. Renal function was evaluated by plasma concentration of creatinine, cystatin C (in 64 patients) and creatinine clearance, calculated according to the Cockcroft-Gault formula. HbA1c measurement and blood pressure monitoring were performed. CCA-IMT was measured at near and far wall of the CCA and of the bulb on both sides and averaged. In 63 hypertensives (72.4%) IMT was over 0.9 mm. These subjects were older (71.17+/-9.72 vs 57.75+/-7.76 years; p<0.0001), had higher pulse pressure (57.45+/-11.73 vs 49.35+/-8.35, p = 0.004), cystatin C concentration (1.25+/-0.34 vs 0.99+/-0.17 mg/l; p = 0.002), higher HbA1c (7.24+/-1.59 vs 6.25+/-1.28, p = 0.01), and lower creatinine clearance (71.28+/-28.32 vs 93.86+/-25.04; p<0.0001) in comparison to patients with IMT <0.9 mm. Groups did not differ with respect to creatinine concentration. The logistic regression analysis showed that CCA-IMT was independently influenced only by age, and the effect of age was stronger in older patients. After exclusion of age, 0.1 mg/l higher concentrations of cystatin C or 10 ml/min lower estimated creatinine clearance were significantly associated with 56% and 34%, respectively, higher probability of CCA-IMT of more than 0.9 mm. Cystatin C concentration seems to be a useful indicator of renal function impairment associated with carotid intima-media thickening. Similar information is obtained when estimated creatinine clearance is used.     

Quantitative measurement of carotid intima-media roughness--effect of age and manifest coronary artery disease

Atherosclerotic changes of the common carotid artery (CCA) may appear like irregularities of the intima-media thickness (abbreviated as IM roughness) in B-mode ultrasound. The purposes of the present study were to investigate whether the CCA IM roughness changes with age and differs between individuals presumed to be healthy and patients with coronary artery disease (CAD). METHODS AND RESULTS: Based on a new automatic identification (AI) program, the segmental intima-media thickness (IMT) and IM roughness of the CCA far wall were measured in B-mode images of 15 younger and 22 older volunteers presumed to be healthy, and 46 patients with known CAD. The mean and maximum CCA IMT were lowest in the young group (0.55+/-0.05; 0.65+/-0.06 mm), higher in the older group (0.77+/-0.16; 0.87+/-0.18 mm) and highest in CAD patients (0.88+/-0.18; 1.01+/-0.27 mm) (P<0.01 among all groups). The CCA IM roughness was greatest by far in the CAD patients (0.075+/-0.02 mm; P<0.01 vs. both groups) and increased only slightly with age (younger: 0.035+/-0.008 mm; older: 0.040+/-0.014 mm; P<0.05). Areas under the curve (AUC) of receiver-operating characteristic curves (ROC) predicting patients with CAD were higher for the CCA IM roughness (0.80) than for the mean (0.66) and maximum IMT (0.71). CONCLUSIONS: It is suggested that the CCA IM roughness increases with age, and helps to discriminate between individuals presumed to be healthy and patients with manifest CAD better than the CCA mean and maximum IMT.     

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.     

Endothelial dysfunction predictor of structural changes of arterial wall in type I diabetes.

AIM: We examined whether alteration in vascular endothelial function exists in non-insulin dependent diabetes mellitus (NIDDM) and whether impaired endothelium-dependent responses in those patients are associated with increased intima-media thickness (IMT), the time sequence of their appearance and the role of individual risk factors in development of structural deterioration of arterial wall. METHODS: Ultrasound technique was used to measure brachial artery flow mediated dilation (FMD) response and carotid IMT in 38 young adults with type I diabetes aged 22-34 years and 35 healthy controls aged 22-36 years. RESULTS: Patients had significantly lower FMD than controls (4.15/2.8/ vs 11.3/3.6/, P<0.0001) and was in all diabetic patients below the mean value of controls. Further, carotid intima-media was in insulin dependent diabetes mellitus (IDDM) patients significantly thicker than in healthy subjects (0.65/0.04 vs 0.56/0.04, P=0.0001) and was related to body mass and body mass index, to the age of patients, the duration of diabetes and several risk variables. In a multivariate model FMD was most significantly and independently associated to IMT. However, significant thickening of intima-media was observed only in patients with progressed deterioration of FMD and it appeared in those subjects with long-lasting disease. IMT was also influenced by urinary albumin excretion and low-density lipoprotein (LDL) cholesterol concentration. CONCLUSIONS: Endothelium dependent FMD response is impaired in IDDM and is associated with increased carotid artery IMT. Significant thickening of intima-media appears in patients with advanced deterioration of FMD that is related to the duration of the disease. These data suggest that advanced endothelial dysfunction in IDDM may predispose to development of morphologic atherosclerotic lesions of arterial wall.     

Chronic inflammation and increased arterial stiffness in patients with cardiac syndrome X.

AIMS: Endothelial dysfunction and subangiographic atheroma have been reported in patients with cardiac syndrome X (CSX) but little is known regarding chronic inflammation and reduced arterial distensibility as pathogenic mechanisms. We assessed whether markers of inflammation and arterial distensibility differ in CSX patients compared to control subjects. METHODS AND RESULTS: We studied 30 consecutive CSX patients (mean age 57+/-6 years, 25 women) and 30 healthy controls (mean age 54+/-8 years, 25 women). High sensitivity C-reactive protein (hs-CRP) levels were significantly higher in patients with CSX compared to controls (2.6 [1.7-4.5] vs 1.5[0.7-2.7] mg/l, P=0.02). Hs-CRP levels correlated with carotid intima-media thickness (IMT) (Spearman's rho=0.51; P=0.013). CSX patients also had significantly increased mean IMT values than controls (P<0.0001). Arterial stiffness and elastic modulus were also significantly increased in CSX patients compared to control subjects (P=0.04 and P=0.04, respectively). Distensibility tended to be lower in CSX patients than controls although this difference did not reach statistical significance. CONCLUSIONS: This study showed for the first time that compared to control subjects, patients with CSX have higher hs-CRP serum levels, increased mean common carotid artery IMT and increased arterial stiffness. The role of these abnormalities in the pathogenesis of CSX deserves investigation.     

Atherosclerosis in rheumatoid arthritis: morphologic evidence obtained by carotid ultrasound

OBJECTIVE: Recent studies have suggested increased cardiovascular disease among patients with rheumatoid arthritis (RA). We undertook this study to obtain morphologic evidence of subclinical atherosclerosis in RA patients. METHODS: We used high-resolution B-mode ultrasound to compare carotid artery intima-media wall thickness (IMT) between 53 postmenopausal women with RA and 53 controls matched by age, sex, and menopause status. No subject in either group had a history of atherosclerosis or its complications. We investigated the association between IMT and relevant clinical and therapeutic variables, including the impact of low-dose corticosteroid therapy (< or = 10 mg/day prednisolone). RESULTS: The mean +/- SD IMT of the left and right common carotid arteries in RA patients was significantly greater than that in controls (0.77 +/- 0.09 mm versus 0.68 +/- 0.14 mm; P < 0.001). Early RA (duration < or = 1 year) was associated with lesser IMT than was RA of longer duration (0.72 +/- 0.03 mm versus 0.78 +/- 0.01 mm; P < 0.04). Prednisolone use was not associated with increased IMT (0.78 +/- 0.02 mm in nonusers versus 0.76 +/- 0.01 mm in users; P = 0.38). CONCLUSION: Our data indicate that RA patients have an ultrasonic marker of early atherosclerosis consistent with an increased risk for atherosclerosis.     

Precocious intima-media thickening in patients with primary Sjögren's syndrome

OBJECTIVE: Systemic lupus erythematosus and rheumatoid arthritis represent independent risk factors for atherosclerosis (ATS), although this may be confounded by continuous pharmacologic treatment. Primary Sj?gren's syndrome (SS) shares several features of these diseases and may therefore represent an interesting model for verifying the presence of accelerated ATS in the absence of pharmacologic interference. The present study therefore used this model to describe the presence of accelerated ATS in a group of young women. METHODS: Thirty-seven untreated white women with primary SS were evaluated clinically and serologically. Carotid and femoral artery intima-media thickness (IMT) was evaluated in the patients and in 35 age-matched healthy women who served as controls. RESULTS: The patients had a higher IMT than did the controls at both the carotid (mean +/- SD 0.82 +/- 0.24 mm versus 0.63 +/- 0.20 mm; P < or = 0.001) and the femoral (0.81 +/- 0.26 mm versus 0.67 +/- 0.23 mm; P < or = 0.019) levels, and had a higher prevalence of carotid intima-media thickening (49% versus 11% of controls; P < or = 0.001). The patient subset with high carotid IMT showed an increased prevalence of leukopenia and circulating anti-SSA antibodies; interestingly, the number of leukocytes was inversely correlated with the level of arterial IMT in patients with SS. Multivariate analysis demonstrated that anti-SSA antibodies were independent predictors of carotid artery thickening, while leukopenia was a predictor of both carotid and femoral artery thickening. CONCLUSION: Subclinical ATS was evident in about one-half of the patients with SS. Its association with some features typical of connective tissue diseases, such as the presence of anti-SSA and leukopenia, suggests that the immune dysregulation characterizing this autoimmune disorder may play a key role in inducing early ATS.     

Increased intima-media thickness of the common carotid artery in primary aldosteronism in comparison with essential hypertension

BACKGROUND: Aldosterone contributes to the accumulation of collagen fibers and extracellular matrix in arterial wall. The aim of this study was to compare intima-media thickness (IMT) of the common carotid artery and carotid bifurcation in patients with primary aldosteronism, essential hypertension and healthy controls. METHODS: Carotid ultrasound studies were carried out in 33 patients aged 42-72 years with primary aldosteronism, 52 patients with essential hypertension and in 33 normotensive controls. RESULTS: The patients with primary aldosteronism had significantly higher IMT of the common carotid artery than patients with essential hypertension and controls (0.987 +/- 0.152 mm; 0.892 +/- 0.154 mm versus 0.812 +/- 0.124 mm; P < 0.001; P < 0.05). There was also significantly higher IMT of the common carotid in patients with essential hypertension compared to control group (0.892 +/- 0.154 mm versus 0.812 +/- 0.124 mm; P < 0.01). The differences between both hypertensive groups remained statistically significant after adjustment for age and 24-h systolic blood pressure (P = 0.001). The differences of the IMT in the carotid bifurcation were statistically significant only between patients with primary aldosteronism and controls (1.157 +/- 0.243 mm versus 0.994 +/- 0.199 mm; P <0.05). CONCLUSION: Patients with primary aldosteronism have increased common carotid IMT compared to the patients with essential hypertension. This finding could be caused by the deleterious effects of aldosterone excess on the fibrosis and thickening of the arterial wall, mainly in the straight segments of vessels.     

Carotid haemodynamic parameters as risk factors for cerebral infarction in Type 2 diabetic patients.

AIMS: The purpose of this study was to investigate the usefulness of carotid haemodynamic parameters, i.e. the resistive index (RI) and the pulsatility index (PI), in estimating the risk of cerebral infarction in Type 2 diabetic patients. METHODS: Three hundred and eighty-two Type 2 diabetic patients (223 men and 159 women; mean age 61 years, range 40-88; 40 had a history of cerebral infarction) and 110 control subjects were analysed in a cross-sectional study. All subjects underwent ultrasonography of the common carotid artery, with determination of intima-media thickness (IMT), RI, and PI. A SMART (Second Manifestations of ARTerial Disease) atherosclerosis risk score was determined for all diabetic patients. RESULTS: The mean values for IMT, RI, and PI were increased in diabetic patients compared with control subjects, and they were significantly elevated in patients with previous cerebral infarction compared with patients without cerebral infarction. (IMT 0.88 +/- 0.22 vs. 0.77 +/- 0.19, P < 0.005; RI 0.77 +/- 0.07 vs. 0.75 +/- 0.06, P < 0.05; PI 1.88 +/- 0.36 vs. 1.71 +/- 0.36, P < 0.01) Significant but weak correlations were found between SMART risk scores and IMT, RI and PI (IMT r = 0.390, P < 0.0001; RI r = 0.346, P < 0.0001; PI r = 0.393, P < 0.0001). The multiple logistic model showed that both the IMT [odds ratio (OR) 6.50, 95% confidence interval (CI) 3.42, 12.34] and the PI (OR 4.16, 95% CI 2.36, 7.34) were independent risk factors for cerebral infarction. The subjects who had an IMT of > 1.0 and a PI > 2.00 had a greater risk of developing a cerebral infarction than did the subjects who had an IMT of < 1.0 and a PI < 2.00 (OR 6.21, 95% CI 2.26, 17.05). CONCLUSIONS: The results of this cross-sectional study showed that the measurement of haemodynamic parameters was useful, together with IMT, in estimating the risk of previous cerebral infarction in Type 2 diabetic patients. The predictive value of these parameters in identifying the risk of future cerebral infarction must await the results of future prospective studies.     

Cardiovascular risk factors and ultrasound evaluation of intima-media thickness at common carotids, carotid bulbs, and femoral and abdominal aorta arteries in patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency

CONTEXT: In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, a tendency for obesity, high insulin, and high 24-h blood pressure levels has been reported in children and adolescents. Increased intima-media thickness (IMT) is considered a measure of subclinical atherosclerosis and a predictor of myocardial infarction and stroke. OBJECTIVE: The objective of the study was to evaluate glucose metabolism, lipid profile, IMT of the abdominal aorta, right and left common carotids, carotid bulbs, and common femoral arteries in adult CAH patients. Subjects: Nineteen (10 females, nine males; 28 +/- 3.5 yr) patients (12 salt wasting and seven simple virilizing) and 19 (10 females, nine males) healthy subjects matched for anthropometric parameters (age, sex, body mass index, smoking habit, waist to hip ratio, and blood pressure). METHODS: Glucose metabolism was studied using the oral glucose tolerance test and the homeostasis model assessment-insulin resistance. The echo-Doppler was used for arterial ultrasound. 17-Hydroxyprogesterone, androstenedione, testosterone, ACTH, plasma renin activity, total and high-density lipoprotein cholesterol, and triglycerides were measured. RESULTS: CAH patients had significantly higher fasting plasma insulin (11.6 +/- 6.20 microU/ml vs 5.18 +/- 2.4 microU/ml; P < 0.0001) and homeostasis model assessment-insulin resistance than controls (2.46 +/- 1.92 vs 1.12 +/- 0.58; P = 0.0033). IMT of the studied arteries was higher in CAH patients than controls. There was no correlation between IMT and cumulative glucocorticoid doses and androgen levels. CONCLUSION: A reduced insulin sensitivity and increased IMT were demonstrated in adults with CAH, who consequently need a follow-up for cardiovascular risk.     

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.     

Personality factors and profiles in variants of irritable bowel syndrome

AIM: To study the association between irritable bowel syndrome (IBS) variants (constipation,diarrhea,or both) and personality traits in non-psychiatric patients. METHODS: IBS was diagnosed using the Rome Ⅱ diagnostic criteria after exclusion of organic bowel pathology. The entry of each patient was confirmed following a psychiatric interview. Personality traits and the score of each factor were evaluated using the NEO Five Factor Inventory. RESULTS: One hundred and fifty patients were studied. The mean age (± SD) was 33.4 (± 11.0) year (62% female). Subjects scored higher in neuroticism (26.25 ± 7.80 vs 22.92 ± 9.54,P < 0.0005),openness (26.25 ± 5.22 vs 27.94 ± 4.87,P < 0.0005) and conscientiousness (32.90 ± 7.80 vs 31.62 ± 5.64,P < 0.01) compared to our general population derived from universities of Iran. Our studied population consisted of 71 patients with Diarrhea dominant-IBS,33 with Constipation dominant-IBS and 46 with Altering type-IBS. Scores of conscientiousness and neuroticism were significantly higher in C-IBS compared to D-IBS and A-IBS (35.79 ± 5.65 vs 31.95 ± 6.80,P = 0.035 and 31.97 ± 9.87,P = 0.043,respectively). Conscientiousness was the highest dimension of personality in each of the variants. Patients with C-IBS had almost similar personality profiles,composed of higher scores for neuroticism and conscientiousness,with low levels of agreeableness,openness and extraversion that were close to those of the general population. CONCLUSION: Differences were observed between IBS patients and the general population,as well as between IBS subtypes,in terms of personality factors. Patients with constipation-predominant IBS showed similar personality profiles. Patients with each subtype of IBS may benefit from psychological interventions,which can be focused considering the characteristics of each subtype.     

Effect of levothyroxine replacement on lipid profile and intima-media thickness in subclinical hypothyroidism: a double-blind, placebo- controlled study

Subclinical hypothyroidism (sHT) is associated with dyslipidemia and enhanced cardiovascular risk. We assessed carotid artery intima-media thickness (IMT, high-resolution ultrasonography) and lipoprotein profile in 45 sHT patients (aged 37 +/- 11 yr) at baseline and after 6 months of randomized, placebo-controlled L-T(4) replacement. In comparison with 32 age- and sex-matched controls, sHT patients had elevated total and low-density lipoprotein (LDL) cholesterol and ApoB levels (P = 0.002, P = 0.0007, and P = 0.01, respectively) and higher mean-IMT values (P < 0.0001). In stepwise regression analysis, mean-IMT was positively related (r(2) = 0.71, P < 0.0001) to age, TSH, and LDL cholesterol. L-T(4) replacement significantly reduced both total and LDL cholesterol (P < 0.0001 for both) and mean-IMT (by 11%, P < 0.0001). The decrement in IMT was directly related to the decrements of both total cholesterol and TSH (P = 0.02 and P = 0.0001, respectively). We conclude that early carotid artery wall alterations are present in sHT patients. Whether such IMT increase is related to an early atherosclerotic involvement of the arterial wall cannot be clearly decided on the basis of the present results. However, the fact that L-T(4) replacement therapy was able to improve both the atherogenic lipoprotein profile and intima-media thickening suggests that lipid infiltration of arterial wall may represent a major mechanism underlying IMT increase in subclinical hypothyroidism.     

Overweight in children is associated with arterial endothelial dysfunction and intima-media thickening

OBJECTIVE: We sought to study arterial endothelial function and carotid intima-media thickness (IMT), both early markers of atherosclerosis, in overweight compared to normal children. DESIGN: Case-control comparison. SUBJECTS: A total of 36 asymptomatic overweight children (body mass index (BMI)>23; mean 25+/-3) aged 9-12 y and 36 age- and gender-matched nonobese healthy children (BMI<21) from a school community. MEASUREMENTS: The key parameters were: BMI, arterial endothelial function (ultrasound-derived endothelium-dependent dilation) and carotid artery IMT. The secondary parameters measured included body fat content, waist-hip ratio (WHR), blood pressures, blood lipids, insulin and glucose. RESULTS: The two groups were well matched for blood pressures, cholesterol and glucose levels, but BMI (P<0.0001), body fat (P=0.001), WHR (P<0.05), fasting blood insulin (P=0.001) and triglyceride levels (P<0.05) were higher in obese children. Overweight was associated with impaired arterial endothelial function (6.6+/-2.3 vs 9.7+/-3.0%, P<0.0001) and increased carotid IMT (0.49+/-0.04 mm vs 0.45+/-0.04 mm, P=0.006). The degree of endothelial dysfunction correlated with BMI (P<0.003) on multivariate analysis. CONCLUSION: Obesity, even of mild-to-moderate degree, is independently associated with abnormal arterial function and structure in otherwise healthy young children.