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(1/1328) Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis.

BACKGROUND: Exposure to risk factors such as hypertension or hypercholesterolemia decreases the bioavailability of endothelium-derived nitric oxide (NO) and impairs endothelium-dependent vasodilation. Recently, a circulating endogenous NO synthase inhibitor, asymmetric dimethylarginine (ADMA), has been detected in human plasma. The purpose of this study was to examine the relationship between plasma ADMA and atherosclerosis in humans. METHODS AND RESULTS: Subjects (n=116; age, 52+/-1 years; male:female ratio, 100:16) underwent a complete history and physical examination, determination of serum chemistries and ADMA levels, and duplex scanning of the carotid arteries. These individuals had no symptoms of coronary or peripheral artery disease and were taking no medications. Univariate and multivariate analyses revealed that plasma levels of ADMA were positively correlated with age (P<0.0001), mean arterial pressure (P<0.0001), and Sigma glucose (an index of glucose tolerance) (P=0.0006). Most intriguingly, stepwise regression analysis revealed that plasma ADMA levels were significantly correlated to the intima-media thickness of the carotid artery (as measured by high-resolution ultrasonography). CONCLUSIONS: This study reveals that plasma ADMA levels are positively correlated with risk factors for atherosclerosis. Furthermore, plasma ADMA level is significantly correlated with carotid intima-media thickness. Our results suggest that this endogenous antagonist of NO synthase may be a marker of atherosclerosis.  (+info)

(2/1328) Menopausal status and distensibility of the common carotid artery.

Although several studies have shown that exogenous estrogens have beneficial effects on arterial characteristics, the effect of endogenous estrogen on the vascular system is still unknown. In this study, distensibility, an indicator of arterial elasticity, of the common carotid artery was compared in pre- and postmenopausal women. The study comprised 93 premenopausal and 93 postmenopausal women of similar age (range, 43 to 55 years). Women were selected from respondents to a mailed questionnaire about the menopause, which was sent to all women aged 40 to 60 years in the Dutch town of Zoetermeer (n=12 675). Postmenopausal women who were at least 3 years past natural menopause or whose menses had stopped naturally before age 48, were age-matched with premenopausal women with regular menses and without menopausal complaints. The selection aimed at maximizing the contrast in estrogen status between pre- and postmenopausal women of the same age. Distensibility of the carotid artery was measured noninvasively with B-mode ultrasound and a vessel wall movement detector system. Arterial distensibility is expressed as the change in arterial diameter (distension, DeltaD) with the cardiac cycle, adjusted for lumen diameter, pulse pressure, and mean arterial blood pressure. Compared with premenopausal women, postmenopausal women had significantly lower arterial distension (DeltaD 370.5 microm [SE 9.5] versus 397.3 microm [SE 9.6]). These results suggest that the distensibility of the common carotid artery is negatively affected by natural menopause in presumed healthy women.  (+info)

(3/1328) TIMP-4 is regulated by vascular injury in rats.

The role of basement membrane-degrading matrix metalloproteinases (MMPs) in enabling vascular smooth muscle cell migration after vascular injury has been established in several animal models. In contrast, the role of their native inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMPs), has remained unproven despite frequent coregulation of MMPs and TIMPs in other disease states. We have investigated the time course of expression and localization of TIMP-4 in rat carotid arteries 6 hours, 24 hours, 3 days, 7 days, and 14 days after balloon injury by in situ hybridization, immunohistochemistry, and Western blot analysis. TIMP-4 protein was present in the adventitia of injured carotid arteries from 24 hours after injury. At 7 and 14 days after injury, widespread immunostaining for TIMP-4 was observed throughout the neointima, media, and adventitia of injured arteries. Western blot analysis confirmed the quantitative increase in TIMP-4 protein at 7 and 14 days. In situ hybridization detected increased expression of TIMP-4 as early as 24 hours after injury and a marked induction in neointimal cells 7 days after injury. We then studied the effect of TIMP-4 protein on the migration of smooth muscle cells through a matrix-coated membrane in vitro and demonstrated a 53% reduction in invasion of rat vascular smooth muscle cells. These data and the temporal relationship between the upregulation of TIMP-4, its accumulation, and the onset of collagen deposition suggest an important role for TIMP-4 in the proteolytic balance of the vasculature controlling both smooth muscle migration and collagen accumulation in the injured arterial wall.  (+info)

(4/1328) Relationship between brain atrophy estimated by a longitudinal computed tomography study and blood pressure control in patients with essential hypertension.

To evaluate the relationship between blood pressure control and the progression of brain atrophy in the elderly, patients with essential hypertension and brain atrophy were longitudinally evaluated using computerized tomography (CT). The study evaluated 48 patients with essential hypertension aged 46-78 years, and 30 sex- and age-matched normotensive control subjects. The extent of brain atrophy as determined by caudate head index (CHI), the inverse cella media index (iCMI), and Evans' ratio (ER) was estimated twice at an interval of 5-9 years (mean, 6.9 years). The mean annual increases in CHI (deltaCHI), iCMI (delta iCMI), and ER (deltaER) were evaluated. Mean blood volume in the common carotid artery (BF) and the decrease in BF per year (deltaBF) were also determined. The deltaCHI, delta iCMI, and deltaER increased with age in the hypertensive subjects as well as the control group across all age groups evaluated. The deltaCHI, delta iCMI, and deltaER were significantly greater in the patients with essential hypertension in their 50 s as compared with the controls. In patients with essential hypertension aged 65 years or older, the deltaCHI, delta iCMI, and deltaER were significantly lower in the group in whom the blood pressure was controlled within the range of borderline hypertension than the groups in which it was controlled in the range of normal or mild hypertension. In the younger patients under the age of 65 with essential hypertension, blood pressure control did not affect the deltaCHI, delta iCMI, and deltaER. The deltaCHI, delta iCMI, and deltaER were significantly correlated with deltaBF in both groups. These findings indicate that control of systolic blood pressure within the range of borderline hypertension may delay the progression of brain atrophy in elderly patients with essential hypertension.  (+info)

(5/1328) Volume flow estimation by colour duplex.

OBJECTIVE: To assess the accuracy of volume blood flow using a digitised colour duplex scanner. DESIGN: Observer-blinded experimental study. MATERIALS AND METHODS: Method comparison was performed with linear regression analysis of 89 paired observations in 11 anaesthetised pigs. A Siemens Sonoline Elegra ultrasound system was used for transcutaneous volume flow estimation using invasive transit time flowmetry by Cardiomed as a reference. RESULTS: For the individual measurement we found a standard error of the estimate (SEE) of 22 ml/min. For the regression line, however, the SEE was only 0.2 ml/min. CONCLUSIONS: Digitised colour-duplex sonography has a volume flow measurement error that is too high for single measurements in the individual patient for the method to be useful in clinical decision making, but sufficient for examinations of groups and comparison of groups.  (+info)

(6/1328) Management of coexisting coronary artery and asymptomatic carotid artery disease: report of a series of patients treated with coronary bypass alone.

BACKGROUND: A retrospective chart review of 94 patients with asymptomatic high-grade carotid stenosis undergoing coronary bypass (and valve replacement in some cases) was performed to determine whether significant carotid lesions can be safely ignored in patients undergoing cardiac surgical procedures. These operations were performed during a 2-year period. PATIENTS AND METHODS: There were 55 men and 39 women, with an age range of 37-89 years. Seventy-one patients had unilateral high-grade carotid stenosis, 17 patients had bilateral high-grade lesions, and six patients had unilateral high-grade stenosis and contralateral occlusion. Associated medical problems were recorded and short-term follow-up was obtained. RESULTS: There was one perioperative stroke and no deaths in this group of patients. CONCLUSIONS: Although these data indicate that high-grade carotid stenoses may be safely ignored during cardiac surgical procedures, a multicentre prospective randomized trial is needed to determine the appropriate treatment of the patient with coexisting carotid and coronary artery disease.  (+info)

(7/1328) Carotid plaque, intima media thickness, cardiovascular risk factors, and prevalent cardiovascular disease in men and women: the British Regional Heart Study.

BACKGROUND AND PURPOSE: B-mode ultrasound is a noninvasive method of examining the walls of peripheral arteries and provides measures of the intima-media thickness (IMT) at various sites (common carotid artery, bifurcation, internal carotid artery) and of plaques that may indicate early presymptomatic disease. The reported associations between cardiovascular risk factors, clinical disease, IMT, and plaques are inconsistent. We sought to clarify these relationships in a large, representative sample of men and women living in 2 British towns. METHODS: The study was performed during 1996 in 2 towns (Dewsbury and Maidstone) of the British Regional Heart Study that have an approximately 2-fold difference in coronary heart disease risk. The male participants were drawn from the British Regional Heart Study and were recruited in 1978-1980 and form part of a national cohort study of 7735 men. A random sample of women of similar age to the men (55 to 77 years) was also selected from the age-sex register of the general practices used in the original survey. A wide range of data on social, lifestyle, and physiological factors, cardiovascular disease symptoms, and diagnoses was collected. Measures of right and left common carotid IMT (IMTcca) and bifurcation IMT (IMTbif) were made, and the arteries were examined for plaques 1.5 cm above and below the flow divider. RESULTS: Totals of 425 men and 375 women were surveyed (mean age, 66 years; range, 56 to 77 years). The mean (SD) IMTcca observed were 0. 84 (0.21) and 0.75 (0.16) mm for men and women, respectively. The mean (SD) IMTbif were 1.69 (0.61) and 1.50 (0.77) mm for men and women, respectively. The correlation between IMTcca and IMTbif was similar in men (r=0.36) and women (r=0.38). There were no differences in mean IMTcca or IMTbif between the 2 towns. Carotid plaques were very common, affecting 57% (n=239) of men and 58% (n=211) of women. Severe carotid plaques with flow disturbance were rare, affecting 9 men (2%) and 6 women (1.6%). Plaques increased in prevalence with age, affecting 49% men and 39% of women aged <60 years and 65% and 75% of men and women, respectively, aged >70 years. Plaques were most common among men in Dewsbury (79% affected) and least common among men in Maidstone (34% affected). IMTcca showed a different pattern of association with cardiovascular risk factors from IMTbif and was associated with age, SBP, and FEV1 but not with social, lifestyle, or other physiological risk factors. IMTbif and carotid plaques were associated with smoking, manual social class, and plasma fibrinogen. IMTbif and carotid plaques were associated with symptoms and diagnoses of cardiovascular diseases. IMTbif associations with cardiovascular risk factors and prevalent cardiovascular disease appeared to be explained by the presence of plaques in regression models and in analyses stratified by plaque status. CONCLUSIONS: IMTcca, IMTbif, and plaque are correlated with each other but show differing patterns of association with risk factors and prevalent disease. IMTcca is strongly associated with risk factors for stroke and with prevalent stroke, whereas IMTbif and plaque are more directly associated with ischemic heart disease risk factors and prevalent ischemic heart disease. Our analyses suggest that presence of plaque, rather than the thickness of IMTbif, appears to be the major criterion of high risk of disease, but confirmation of these findings in other populations and in prospective studies is required. The association of fibrinogen with plaque appears to be similar to its association with incident cardiovascular disease. Further work elucidating the composition of plaques using ultrasound imaging would be helpful, and more data, analyzed to distinguish plaque from IMTbif and IMTcca, are required to understand the significance of thicker IMT in the absence of plaque.  (+info)

(8/1328) Thromboembolic events predispose the brain to widespread cerebral infarction after delayed transient global ischemia in rats.

BACKGROUND AND PURPOSE: Transient distal platelet accumulation after common carotid artery thrombosis (CCAT) leads to hemodynamic, metabolic, and molecular events that may influence the response of the postthrombotic brain to secondary insults. We investigated how a thromboembolic insult would affect histopathological outcome when combined with an ischemic insult induced 24 hours later. METHODS: Three groups of rats underwent either (1) CCAT+10 minutes of normothermic 2-vessel occlusion (n=6), (2) CCAT+sham ischemia procedures (n=6), or (3) sham CCAT procedures+10 minutes of 2-vessel occlusion (n=6). At 7 days, rats were perfused for quantitative histopathological and immunocytochemical analysis. RESULTS: Rats undergoing combined insults (group 1) had significantly larger areas of ischemic injury (P<0.05) within the cerebral cortex, striatum, and thalamus compared with the other, single-injury groups. Increased ischemic damage included selective neuronal necrosis, infarction, and focal hemorrhage. By means of glial fibrillary acidic protein immunocytochemistry and lectin histochemistry, reactive astrocytes and microglia were found to be associated with widespread tissue necrosis. In contrast, infrequent infarction or CA1 hippocampal neuronal necrosis was observed in groups 2 and 3, respectively. CONCLUSIONS: A prior thromboembolic event is a risk factor for widespread cerebral infarction and hemorrhage when combined with a delayed ischemic insult. The understanding of what factors enhance the susceptibility of the postthrombotic brain to secondary insults may aid in the development of neuroprotective strategies to be applied after transient ischemic attacks to prevent the initiation of stroke.  (+info)