Detection of the phosphorylcholine epitope in streptococci, Haemophilus and pathogenic Neisseriae by immunoblotting

Intimal-medial thickness (IMT) of the extracranial carotid arteries measured by B-mode ultrasonography has been used as a marker of systemic and coronary atherosclerosis. Previous studies have indicated that maximum and mean carotid IMT are significantly correlated with the extent and severity of coronary artery disease (CAD), but the clinical usefulness of these markers is limited because they are neither specific nor sensitive enough to identify patients with or without significant CAD. The correlation of a new IMT marker, variance of IMT, with coronary risk factors and coronary atherosclerosis was investigated in 200 patients who underwent carotid ultrasonography and coronary angiography. IMT was measured in 16 sites of the extracranial carotid arteries for the calculation of mean, maximum and variance of IMT. Univariate analysis showed that these three indexes were significantly correlated with age, serum lipoprotein (a) and hypertension. However, age was correlated weakly with variance of IMT. There were significant gender differences in the mean and maximum IMT but not in the variance. There were also significant correlations of mean IMT with smoking, and maximum and variance of IMT with high-density lipoprotein. Multiple logistic regression analysis in 100 age and sex matched patients indicated that the only significant predictor for CAD in this subgroup was variance of IMT (odds ratio = 1.6). These results indicated that each risk factor causes different morphologic manifestations in the carotid atherosclerotic lesion. Variance of IMT, which represents the irregularity of carotid IMT, was correlated well with CAD and appears to be useful for assessing systemic and coronary atherosclerosis.     

Circulating cell adhesion molecules are correlated with ultrasound-based assessment of carotid atherosclerosis

Although cellular adhesion molecules (CAMs) are hypothesized to play an important role in atherogenesis, the relationship between CAMs and systemic atherosclerosis is uncertain. Among 92 outpatients (48 men; mean+/-SD age, 65+/-9 years), we evaluated the association of soluble vascular CAM-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) with carotid intimal-medial thickness (IMT), an index of early atherosclerosis. All subjects underwent a 2-dimensional ultrasound examination of both carotid arteries at the distal common carotid arteries and bifurcation. sVCAM-1 and sICAM-1 levels measured by enzyme-linked immunosorbent assay were significantly correlated with mean IMT of the common carotid artery (r=0.34 and r=0.30, respectively; P<0.01) and carotid bifurcation (r=0.31 and r=0.26, respectively; P<0.05), whereas sVCAM-1 was also positively associated with maximal carotid IMT (r=0.35, P<0.01). Adjustment for age attenuated the association between sVCAM-1 and common (r=0.16, P=0.13) and bifurcation (r=0.18, P=0.07) carotid IMT but had minimal effect on the associations between sICAM-1 and carotid measurements (r=0.32, P<0.01; r=0.23, P<0.05; for common and bifurcation IMT, respectively). Age-adjusted sICAM-1 levels increased in a stepwise fashion across common carotid IMT tertiles (253+/-27 versus 275+/-24 versus 384+/-26 pg/mL for the lowest, intermediate, and highest IMT tertiles, respectively; P<0.01). A similar trend was also found between sVCAM-1 levels and common carotid IMT tertiles (625+/-60 versus 650+/-53 versus 714+/-58 pg/mL; P<0.15). These associations were minimally affected in analyses adjusting for hypertension, diabetes, smoking, low and high density lipoprotein cholesterol, lipoprotein(a), and homocysteine, or in a subgroup analysis limited to those with no prior history of atherothrombotic disease. These data demonstrate a positive association between serum CAMs with carotid IMT and further support the hypothesis that systemic inflammation may have a role in atherosclerotic lesion development.     

Regional distribution of 5alpha-reductase type 1 and type 2 mRNA along the human epididymis

BACKGROUND AND PURPOSE: In women, symptoms of coronary artery disease are delayed by 10 to 15 years in comparison with men, most likely because of the protective effect of ovarian hormones. This report compares the prevalence and degree of carotid atherosclerosis between 292 premenopausal women and 294 women at 5 to 8 years after menopause. METHODS: Scans were performed in the same laboratory over the same time period for both groups. Intima-media thickness (IMT) was averaged across the common, bulb, and internal carotids. The plaque index summarized degree of focal plaque based on the size and number of plaques throughout both carotid systems. RESULTS: Mean IMT was 0.69 mm for premenopausal women and 0.77 mm for postmenopausal women (P < 0.001). Prevalence of plaque was 25% among premenopausal women and 54% among postmenopausal women (P < 0.001). In both premenopausal and postmenopausal women, risk factors measured before menopause were associated with carotid atherosclerosis. Premenopausal risk factors independently associated with IMT were higher pulse pressure (P < 0.001), triglycerides (P = 0.002), body mass index (P < 0.001), and study group (a surrogate for both age and menopausal status; P < 0.001). Premenopausal risk factors independently associated with focal plaque were ever smoking (P = 0.002), higher pulse pressure (P = 0.028), higher LDL (P = 0.003), age at baseline (P = 0.050), and study group (P < 0.001). CONCLUSIONS: Subclinical carotid atherosclerosis can be observed in middle-aged women. Risk factors measured before menopause are clearly associated with subclinical disease measured both concurrently and at 5 to 8 years after menopause.     

Blood viscosity and elevated carotid intima-media thickness in men and women: the Edinburgh Artery Study

BACKGROUND: Several hemostatic and rheological factors have been associated with incident cardiovascular events. However, there have been no reports on the relationship of rheological factors with early atherosclerosis and very few on hemostatic factors. We therefore studied the relationship between these factors and carotid intima-media thickness (IMT). METHODS AND RESULTS: The Edinburgh Artery Study measured fibrinogen, tissue plasminogen activator (tPA), fibrin D-dimer, von Willebrand factor (vWF), blood and plasma viscosities, and hematocrit as part of its baseline examination during 1988-1989. At the 5-year follow-up, valid measurements of IMT had been recorded in 1106 men and women 60 to 80 years old. In men, blood viscosity (P< or =.001) and its major determinants, plasma viscosity, fibrinogen (both P< or =.01), and hematocrit (P< or =.05), were all linearly related to IMT. Furthermore, blood viscosity, fibrinogen (both P< or =.01), and plasma viscosity (P< or =.05) remained significantly associated on multivariate analysis. Correcting blood viscosity to a standard hematocrit of 45% had little effect on its association. In men, there was a significantly increased risk of having an IMT above versus below the upper quartile of its distribution (1.05 mm) for SD increases in blood viscosity (P< or =.01), fibrinogen, corrected blood viscosity, and plasma viscosity (all P< or =.05). With the exception of plasma viscosity, these risks were unaffected by adjustment for other common cardiovascular risk factors. No significant associations were found between any of the hemorheological factors and IMT in women or for tPA, fibrin D-dimer, or vWF in either sex. CONCLUSIONS: These findings suggest that in men, blood viscosity and its major determinants are associated not only with incident cardiovascular events but also with the early stages of atherosclerosis. This may be one explanation for the link between rheological factors and events.     

Stress-induced pulse pressure change predicts women's carotid atherosclerosis

BACKGROUND AND PURPOSE: Individuals who exhibit large increases in blood pressure and heart rate during mental stress may be at risk for accelerated atherosclerosis. This report evaluates the association between stress-induced hemodynamic responses and carotid atherosclerosis in 254 healthy postmenopausal women. METHODS: The magnitude of change in blood pressure and heart rate from rest to public speaking and mirror image tracing, two stressful tasks, was measured. Average intima-media thickness (IMT) and focal plaque in the common carotid artery, bulb, and internal carotid artery were measured with the use of duplex ultrasonography on average 2.3 years later. RESULTS: The average IMT was 0.77 mm, with a range of 0.60 to 1.37; 52.5% had at least one plaque. Correlational analysis showed that greater IMT was associated with greater pulse pressure change during mental stress (r = 0.17, P < 0.01). Statistical adjustments for possible confounders (age, hormone replacement therapy use, resting pulse pressure, smoking status, and triglyceride levels) did not alter the results. The plaque index was associated with greater pulse pressure change during the mirror image tracing task (odds ratio = 1.47, P = 0.01) for women with a plaque score of > or = 2 versus 1 or 0, adjusted for possible confounders. CONCLUSIONS: Mental stress-induced pulse pressure changes may influence the development of early atherosclerosis in the carotid artery of women. Widening of pulse pressure during stress, as well as at rest, may be a marker of compromised compliance in the vessel wall.     

Indications for carotid endarterectomy in patients with symptoms: when, where?

Carotid endarterectomy (CEA) is one of the most commonly used surgical methods in the treatment of cerebral stroke with both therapeutic and also prophylactic implications. CEA has been used in surgical practice for 40 years. At the beginning it was very popular and was widely used. Later, the opposite extreme was reached, and its therapeutic efficacy was denied unjustifiably. However, at the beginning of the ninetieth three large controlled studies were completed (North American Symptomatic Carotid Endarterectomy Trial, European Carotid Surgery Trial and Veterans Administrations Symptomatic Trial) and the results of these trials were the basis for establishing the solid criteria for the surgical procedure in some groups of symptomatic patients with stenosis of the internal carotid artery. Thus, CEA was in again. In accordance with the attitudes of the American Association Ad Hoc Committee (1995), evidenced indications for CEA in patients with symptomatic stenosis of the internal carotid artery (in the group with surgical risk less than 6%) include (a) single or recurrent episodes of TIA in the last 6 months, "crescendo" TIA combined with carotid stenosis > 70% with or without plaque ulceration, with or without antiplatelet therapy, and (b) mild stroke in last 6 months with carotid stenosis > 70% with or without plaque ulceration, with or without antiplatelet therapy. The authors report their experience and results of a six-month pilot study of 301 patients, of whom 248 were operated on for symptomatic carotid stenosis with low combined perioperative morbidity and mortality (0.6%). Also, indications for surgical reconstruction of carotid and coronary arteries in patients with marked signs of atherosclerosis in both arterial systems are discussed.     

Association of hormone replacement therapy and carotid wall thickness in women with and without diabetes

OBJECTIVE: Atherosclerosis is the major underlying cause of death for women with type 2 diabetes. We examined the relationship between use of postmenopausal hormone replacement therapy(HRT) and subclinical atherosclerosis among women with type 2 diabetes, impaired glucose tolerance (IGT), and normal glucose tolerance. RESEARCH DESIGN AND METHODS: A cross-sectional analysis was conducted among 623 postmenopausal women in the Insulin Resistance Atherosclerosis Study (IRAS). Current users of HRT, n = 200, were compared with 104 former users and 319 never users. Intimal-medial wall thicknesses (IMTs) of the common carotid (CCA) and internal carotid (ICA) arteries were used as measures of atherosclerosis. RESULTS: Significant differences between HRT user groups were noted for certain demographic, socioeconomic, and lifestyle factors. After adjustment for these and other coronary heart disease risk factors, current users had a 69 microm thinner ICA IMT than never users (P = 0.06). Former users had a 96 pm thinner ICA IMT than never users (P = 0.03). No significant difference was observed for the CCA. Although women with type 2 diabetes had thicker carotid IMT than women without diabetes, the association between HRT use and thinner IMT was similar in both groups. The difference between current and never users was attenuated by adjustment for HDL and LDL cholesterol. Neither duration of HRT use nor HRT regimen was associated with IMT in either artery. CONCLUSIONS: This analysis suggests that current and former use of HRT is associated with reduced atherosclerosis and that women with type 2 diabetes may receive the same benefit from HRI as women without diabetes.     

Increased common carotid intima-media thickness. Adaptive response or a reflection of atherosclerosis? Findings from the Rotterdam Study

BACKGROUND AND PURPOSE: Carotid intima-media thickness (IMT) measurements are used widely to study atherosclerosis. Some have suggested that an increased IMT reflects a nonatherosclerotic adaptive response to changes in shear stress and tensile stress. This stems from the hypothesis that changes in shear stress and subsequently in lumen diameter are followed by changes in IMT to keep tensile stress constant. We studied the relation of common carotid IMT to common carotid end-diastolic lumen diameter and tensile stress, as approximated by mean arterial pressure (lumen diameter/IMT)]. METHODS: A cross-sectional analysis was performed with data obtained from the first 1715 participants in the Rotterdam Study, a population-based cohort study among 7983 subjects aged 55 years and over who underwent ultrasonographic examination of the carotid arteries. End-diastolic lumen diameter and IMT of the common carotid arteries were evaluated and quantified. RESULTS: With increasing IMT, inner and outer lumen diameters increased gradually, and beyond an IMT of 1.10 mm, the inner lumen diameter decreased. Tensile stress increased with increasing lumen diameter instead of being constant. The lumen-to-IMT ratio was constant across levels of mean arterial pressure. CONCLUSIONS: Our findings are compatible with the view that at lower degrees of IMT, the thickening appears to reflect an equilibrium state in which the effects of pressure and flow on the arteries are in balance, given a characteristic relation between shear stress and local transmural pressure. Beyond a certain level, IMT more likely may represent atherosclerosis. Regardless of whether common carotid IMT reflects local atherosclerosis, it may still serve as a graded marker for cardiovascular risk.     

Ultrasound and lipoproteins as predictors of lipid-rich, rupture-prone plaques in the carotid artery

The aim of this review is to summarize present knowledge of the ultrasonic detection and determinants of carotid atherosclerosis with lipid-rich cores and to review the evidence that these measures of plaque type may predict cerebral events. With the use of high-resolution ultrasound B-mode imaging, carotid plaques evaluated as only weakly reflecting the ultrasound beam (echolucent) have been associated with a higher risk of neurological events than are plaques reflecting the ultrasound signal strongly (echorich). Histologically, these echolucent plaques have a higher content of lipid and hemorrhage than do echorich plaques, which contain more calcification and fibrous tissue. Findings in the coronary arteries indicate that a lipid-rich plaque with a thin, fibrous cap is more vulnerable, is more prone to rupture, and cause symptoms compared with fibrous plaques. A search for determinants in the blood for these vulnerable plaques suggests that low density lipoprotein (LDL) cholesterol is the best lipid predictor for the extent of atherosclerosis, whereas triglyceride-rich lipoproteins in particular seem to predict an echolucent plaque. Lowering of LDL cholesterol and triglyceride-rich lipoproteins in plasma is associated with reduced progression of coronary atherosclerosis and coronary events. LDL cholesterol reduction is also associated with a reduced stroke rate. These improvements in the prognosis are thought to be the result of a reduction in the lipid content of the plaques, making them more stable and resistant to rupture rather than an actual reduction in plaque volume and degree of stenosis. In conclusion, it appears that ultrasound B-mode imaging as well as lipoproteins presumably may predict dangerous and rupture-prone, lipid-rich plaques in the carotid arteries, thereby being potential diagnostic tools in the prevention of neurological events.     

Compensatory increase in common carotid artery diameter. Relation to blood pressure and artery intima-media thickness in older adults. Cardiovascular Health Study

BACKGROUND AND PURPOSE: Common carotid artery (CCA) diameter is thought to increase as a consequence of hypertension and may increase as the thickness of the arterial wall increases. The purpose of this study was to determine CCA dimensions and correlate them with clinical features. METHODS: We performed a cross-sectional, community-based study of adults 65 years of age and older, measuring inner and outer diameter of the CCA in vivo with carotid sonography. Findings were correlated against risk factors for atherosclerosis, CCA intima-media thickness (IMT), and echocardiographically determined left ventricular (LV) mass. RESULTS: Independent variables showing strong positive associations with outer and inner CCA diameter included age, male sex, height, weight, and systolic blood pressure. As an independent variable, LV mass (r = .40 and r = .37, respectively; P < .00001) had a strong positive relation to inner and outer CCA diameters. The relationship between diameter and IMT was different. In a model that controlled for age, sex, and estimated LV mass, an increase of 1 mm in CCA IMT corresponded to a 1.9 mm increase in the outer diameter of the artery (P < .00001) but was not significantly related to the inner diameter (slope = +0.07 mm; P = .26). CONCLUSIONS: Increase in the outer diameter of the CCA is associated with subject size, sex, age, echocardiographically estimated LV mass, and CCA IMT. Increases in internal diameter of the CCA have similar relationships but are not related to IMT. This supports the hypothesis that the human CCA dilates as the thickness of the artery wall increases.     

Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987-1993

Few studies have determined whether greater carotid artery intima-media thickness (IMT) in asymptomatic individuals is associated prospectively with increased risk of coronary heart disease (CHD). In the Atherosclerosis Risk in Communities Study, carotid IMT, an index of generalized atherosclerosis, was defined as the mean of IMT measurements at six sites of the carotid arteries using B-mode ultrasound. The authors assessed its relation to CHD incidence over 4-7 years of follow-up (1987-1993) in four US communities (Forsyth County, North Carolina; Jackson, Mississippi; Minneapolis, Minnesota; and Washington County, Maryland) from samples of 7,289 women and 5,552 men aged 45-64 years who were free of clinical CHD at baseline. There were 96 incident events for women and 194 for men. In sex-specific Cox proportional hazards models adjusted only for age, race, and center, the hazard rate ratio comparing extreme mean IMT (> or = 1 mm) to not extreme (< 1 mm) was 5.07 for women (95% confidence interval 3.08-8.36) and 1.85 for men (95% confidence interval 1.28-2.69). The relation was graded (monotonic), and models with cubic splines indicated significant nonlinearity. The strength of the association was reduced by including major CHD risk factors, but remained elevated at higher IMT. Up to 1 mm mean IMT, women had lower adjusted annual event rates than did men, but above 1 mm their event rate was closer to that of men. Thus, mean carotid IMT is a noninvasive predictor of future CHD incidence.     

Ultrasonographically assessed maximum carotid artery wall thickness in Mexico City residents and Mexican Americans living in San Antonio, Texas. Association with diabetes and cardiovascular risk factors

Measurements of carotid artery wall thickness are often used as a surrogate for atherosclerosis. However, few studies have performed these measurements in populations of Mexican origin. Since Mexicans in Mexico City consume high-carbohydrate diets and have carbohydrate-induced dyslipidemia (high triglyceride and low HDL cholesterol levels) compared with Mexican Americans living in San Antonio, Tex, we questioned whether they also had more atherosclerosis than San Antonio Mexican Americans. Mean maximum intimal-medial thickness (IMT) of the common (CCA) and internal (ICA) carotid arteries were measured in 867 subjects aged 35 to 64 years (40% men) in two Mexican-origin populations, one from San Antonio (n = 202) and the other from Mexico City (n = 665). IMT's in the two cities were compared, and their associations with cardiovascular risk factors were analyzed. Older age, male sex, high levels of total cholesterol, low levels of HDL cholesterol, and high systolic blood pressure were positively associated with both CCA IMT and ICA IMT. Cigarette smoking was significantly associated with ICA IMT. CCA and ICA IMTs in diabetic subjects were thicker than in nondiabetic subjects in both men and women (all P < = .05). CCA IMT was thicker in the San Antonio than the Mexico City subjects after adjustment for cardiovascular risk factors (0.81 versus 0.76 mm in men and 0.77 versus 0.71 mm in women; P < .001 for city difference). San Antonio men also had thicker ICA IMT than their counterparts in Mexico City (0.88 versus 0.83 mm), but the reverse was true for women (0.73 versus 0.77 mm; interaction between sex and city, P < .05). Our results indicate that men had higher carotid IMTs than women. CCA IMT was thicker in San Antonio Mexican Americans than in Mexico City residents. The differences in ICA IMTs between San Antonio and Mexico City were inconsistent. Thus, since Mexico City residents consume high-carbohydrate diets, the data do not support an atherogenic effect of such diets. The interaction between sex and city on ICA IMT deserves further study.     

Lacunar infarcts defined by magnetic resonance imaging of 3660 elderly people: the Cardiovascular Health Study

OBJECTIVE: To identify risk factors for and functional consequences of lacunar infarct in elderly people. METHODS: The Cardiovascular Health Study (CHS) is a longitudinal study of people 65 years or older, in which 3660 participants underwent cranial magnetic resonance imaging (MRI). Neuroradiologists read scans in a standard fashion without any clinical information. Lacunes were defined as subcortical areas consistent with infarcts measuring 3 to 20 mm. In cross-sectional analyses, clinical correlates were contrasted among groups defined by MRI findings. RESULTS: Of the 3660 subjects who underwent MRI, 2529 (69%) were free of infarcts of any kind and 841 (23%) had 1 or more lacunes without other types present, totaling 1270 lacunes. For most of these 841 subjects, their lacunes were single (66%) and silent (89%), namely without a history of transient ischemic attack or stroke. In multivariate analyses, factors independently associated with lacunes were increased age, diastolic blood pressure, creatinine, and pack-years of smoking (listed in descending order of strength of association; for all, P < .005), as well as maximum internal carotid artery stenosis of more than 50% (odds ratio [OR], 1.81; P < .005), male sex (OR, 0.74; P < .005), and history of diabetes at entrance into the study (OR, 1.33; P < .05). Models for subgroups of single, multiple, silent, and symptomatic lacunes differed only minimally. Those with silent lacunes had more cognitive, upper extremity, and lower extremity dysfunction not recognized as stroke than those whose MRIs were free of infarcts. CONCLUSIONS: In this group of older adults, lacunes defined by MRI are common and associated with factors that likely promote or reflect small-vessel disease. Silent lacunes are also associated with neurologic dysfunction.     

Race-ethnicity and determinants of carotid atherosclerosis in a multiethnic population. The Northern Manhattan Stroke Study

BACKGROUND AND PURPOSE: Risk factors for carotid atherosclerosis have been studied in white populations but infrequently in multiethnic cohorts. The aim of this study was to determine the importance of race-ethnicity and other factors associated with carotid atherosclerosis in a mixed population of Hispanics, blacks, and whites. METHODS: As part of the Northern Manhattan Stroke Study, 526 stroke-free community residents (aged > or = 40 years; 41% men, 59% women; 46% Hispanic, 31% black, 23% white) were recruited through random-digit dialing and had vascular risk factor evaluations. Maximum internal carotid artery plaque thickness (MICPT) was measured with B-mode ultrasound. The frequency distribution of MICPT was examined in the three race-ethnic groups, and multivariate regression was performed to identify factors that were independently associated with MICPT. RESULTS: Mean MICPT in the entire sample was 1.5 +/- 1.4 mm, increased directly with age, and was greater in whites and blacks than Hispanics. Other independent determinants of MICPT included smoking, glucose, LDL cholesterol, and hypertension. After we controlled for these covariates, Hispanic (versus non-Hispanic) race-ethnicity was still an independent determinant of less carotid plaque. There was a significant interaction between race-ethnicity and LDL cholesterol, with a greater effect of increasing LDL cholesterol among Hispanics. CONCLUSIONS: Atherosclerotic risk factors were predictive of MICPT in this mixed-ethnic cohort. Hispanics had significantly less carotid plaque after adjustment for other known risk factors, but they also had a greater impact of increasing LDL cholesterol.     

Proinsulin and insulin concentrations in relation to carotid wall thickness: Insulin Resistance Atherosclerosis Study

BACKGROUND AND PURPOSE: Insulin resistance and hyperinsulinemia have been associated with atherosclerosis. Recent attention has focused on the possible role of proinsulin because most radioimmunoassays for insulin cross-react with proinsulin. Therefore, it is not known which of the two, insulin per se or proinsulin, is more strongly related to atherosclerosis. METHODS: We examined the relation between fasting proinsulin, fasting split proinsulin, fasting and 2-hour insulin (after oral glucose load), and intima-media wall thickness (IMT) in the common carotid artery (CCA) and internal carotid artery (ICA) in 985 nondiabetic subjects from the Insulin Resistance Atherosclerosis Study, a multiethnic study of insulin resistance and atherosclerosis. RESULTS: In the overall population, a weak but significant relation between proinsulin and CCA IMT was observed (r=0.07, P=0.029). However, the relation between proinsulin and IMT was stronger in Hispanics and non-Hispanic whites than in African Americans. In non-Hispanic whites and Hispanics, significant correlations between CCA and proinsulin (r=0.087) and between ICA and proinsulin (r=0.101), split proinsulin (r = 0.092), and fasting insulin (r = 0.087) were observed. The significant correlations became more attenuated (and nonsignificant) after adjustment for cardiovascular risk factors, especially plasminogen activator inhibitor-1 (PAI-1). CONCLUSIONS: The association between proinsulin and IMT, while weak, appears to be stronger than the association between insulin and IMT. Adjustment for PAI-1 markedly attenuated the association between proinsulin and IMT, suggesting a possible mediating role for PAI-1 in this association. It is possible that proinsulin may represent a marker of atherosclerosis rather than a causal factor for atherosclerosis. Studies of the insulin resistance syndrome and atherosclerosis that use insulin as a surrogate for insulin resistance should consider the use of specific insulin assays as well as determination of proinsulin concentrations.     

Relations of intimal-medial thickness among sites within the carotid artery as evaluated by B-mode ultrasound. ARIC Investigators. Atherosclerosis Risk in Communities

BACKGROUND AND PURPOSE: B-mode ultrasound is a widely used technique for the clinical and epidemiological assessment of carotid atherosclerosis. This article describes the relation between arterial intimal-medial thickness (IMT) at different sites within the extracranial carotid artery. METHODS: IMT was measured by B-mode real-time ultrasound as an index of atherosclerotic involvement in the extracranial carotid arteries as part of the population-based Atherosclerosis Risk in Communities (ARIC) study. The relation between IMT at different sites was described by correlation coefficients and percentile regression techniques based on between 4034 and 9386 pairs of measurements (variation in sample size depending on the paired sites). RESULTS: Increased IMT at one site was associated with increased IMT at other sites. The correlation between right and left IMT at the same anatomic location in the carotid artery ranged from .34 to .49; the correlation at different anatomic locations in the carotid artery on the same side ranged from .25 to .43. The distribution of IMT, described by the percentiles of IMT at the inference site as a function of IMT at the index site, showed constricted percentiles of IMT at the inference site for small IMT at the index site and an increase in the spread of percentiles with increasing IMT. CONCLUSIONS: Although increased carotid IMT at one site is positively associated with thickened walls at other carotid sites, the ability to accurately predict wall thickness at a site given the wall thickness at other sites is modest. The general association between sites supports the systemic nature of atherosclerosis, while the lack of tight agreement between sites supports the focal nature of the atherosclerotic process.     

Decrease in glomerular filtration rate in Japanese patients with type 2 diabetes is linked to atherosclerosis

OBJECTIVE: We assessed the effects of atherosclerosis on the glomerular filtration rate (GFR) in patients with type 2 diabetes and who had micro- or normoalbuminuria. RESEARCH DESIGN AND METHODS: A total of 61 Japanese patients with type 2 diabetes were recruited from inpatients of Osaka City University Hospital. They ranged in age from 40 to 69 years (28 men and 33 women). Each subject collected a 24-h urine sample for quantitative analysis of albumin. Absence of albuminuria was defined as a urinary albumin excretion level of <30 mg/24 h (n = 36) and microalbuminuria as a level of 30-300 mg/24 h. The GFR was estimated using 99mTc diethylenetriamine pentaacetic renogram method. As indexes of atherosclerosis, we measured the intimal-medial thickness (IMT) and distensibility of the carotid artery using high-resolution B-mode ultrasonagraphy and an echo-tracking system. We measured the resistance index (RI) of the renal interlobar arteries by pulsed Doppler sonography. RESULTS: The clinical characteristics of type 2 diabetic patients with and without microalbuminuria did not differ except for duration of diabetes, which was longer in the patients with microalbuminuria. GFR also did not differ between the patients with and without microalbuminuria. GFR was significantly correlated with the patient's age (r = -0.256, P < 0.05), carotid IMT (r = -0.326, P < 0.05), carotid stiffness beta (r = -0.449, P < 0.001), and renal arterial RI (r = -0.365, P < 0.05). In multiple regression analysis, independent factors associated with GFR were carotid IMT (R2 = 0.108, P = 0.0102), carotid stiffness beta (R2 = 0.208, P = 0.0003), and renal artery RI (R2 = 0.130, P = 0.0043). CONCLUSIONS: The decline in GFR in type 2 diabetic patients in the early stages of nephropathy may be due in part to atherosclerosis.     

Impaired glucose tolerance, type 2 diabetes, and carotid wall thickness: the Insulin Resistance Atherosclerosis Study

OBJECTIVE: To assess whether people with impaired glucose tolerance (IGT) exhibit an increased risk of atherosclerosis as measured by the thickness of the carotid artery. RESEARCH DESIGN AND METHODS: We examined the relationship between glucose tolerance status and subclinical atherosclerosis in the Insulin Resistance Atherosclerosis Study (IRAS). The IRAS is an epidemiological study of 1,625 Hispanic, African-American, and white men and women, with approximately equal numbers of subjects with normal glucose tolerance (NGT), IGT, and type 2 diabetes as assessed by an oral glucose tolerance test. Half of those with diabetes were previously unaware of their condition and were defined as having new diabetes. Persons using insulin were excluded. The intima-media thickness (IMT) of the common carotid artery (CCA) and internal carotid artery (ICA) was measured as an index of subclinical atherosclerosis using B-mode ultrasonography. RESULTS: Adjusted for demographics and smoking, CCA-IMT increased most notably at the level of established diabetes (802, 822, 831, and 896 microm for NGT, IGT, new diabetes, and established diabetes, respectively). Adjustment for coronary heart disease (CHD) risk factors, which tended to worsen across glucose tolerance category, further minimized the slightly graded relationship. The relationship with the ICA-IMT was steeper and again suggested that the increased wall thickness is associated with diabetes, not with IGT. The relationship between glucose tolerance category and IMT was similar in men and women. CONCLUSIONS: We observed considerably greater IMT among persons with established diabetes but no significant increase in persons with IGT. These data suggest that the increased risk of CHD observed in persons with diabetes may largely develop after the onset of overt diabetes.     

B-mode ultrasound assessment of pravastatin treatment effect on carotid and femoral artery walls and its correlations with coronary arteriographic findings: a report of the Regression Growth Evaluation Statin Study (REGRESS)

OBJECTIVES: In this B-mode ultrasound study we assessed pravastatin treatment effects on carotid and femoral artery walls and investigated the correlations between the state and evolution of peripheral and coronary atherosclerosis. BACKGROUND: The Regression Growth Evaluation Statin Study (REGRESS) was an 11-center, 2-year, double-blind, placebo-controlled, prospective study of 885 men with coronary artery disease (CAD) (total cholesterol 4 to 8 mmol/liter). The study primarily investigated pravastatin treatment effects on the coronary lumen. This report focuses on the 255 patients who participated in the REGRESS ultrasound study. METHODS: Carotid and femoral artery walls were imaged at baseline and at 6, 12, 18 and 24 months. Pravastatin treatment effect was defined as the difference in progression of the combined intima-media thicknesses (IMT) between treatment groups. RESULTS: Pravastatin treatment effects were highly significant (combined IMT: p = 0.0085; combined far wall IMT: p < 0.0001; common femoral artery far wall IMT: p = 0.004). Correlations between the IMTs of the arterial wall segments ranged from -0.17 to 0.81. Baseline correlations between IMT and percent coronary lumen stenoses ranged from 0.23 to 0.36. Baseline IMT correlated with the mean coronary segment diameter (r = -0.32, p = 0.001) and minimal coronary obstruction diameter (r = -0.27, p = 0.005). There were no individual correlations between IMT and coronary lumen variables (p > 0.30). CONCLUSIONS: Pravastatin treatment effects on carotid and femoral artery walls were observed. B-mode ultrasound imaging studies of peripheral arterial walls could not describe the state and evolution of the coronary lumen in the individual patient, but proved to be a highly suitable tool for the assessment of antiatherosclerotic properties of agents.