Neck circumference predicts development of carotid intima-media thickness and carotid plaque: A community-based longitudinal study

Background and aimsCarotid intima-media thickness (C-IMT) is an important index for evaluating subclinical atherosclerosis. Neck circumference (NC), a new anthropometric index of the upper body fat, is closely related to cardiovascular disease (CVD) and CVD risk factors. This study investigated the relationship between NC, C-IMT, and carotid plaque in a community-based cohort.Methods and resultsParticipants recruited from Shanghai communities were followed up for 1.1–2.9 years. All participants underwent anthropometric and biochemical measurements. Elevated NC was defined as NC ≥ 38.5 cm and NC ≥ 34.5 cm in men and women, respectively. Elevated C-IMT, determined by ultrasound, was defined as a level higher than the 75th percentile in the study population (>0.75 mm). In total, 1189 participants without carotid plaque at baseline were included, with an average age of 59.6 ± 7.3 years. After a mean follow-up of 2.1 ± 0.2 years, 203 participants developed carotid plaques. After adjusting for various atherosclerosis risk factors, the logistic regression showed that the higher NC group had a significantly greater risk of developing carotid plaque than the lower NC group (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.12–2.14; P = 0.008). Of those without carotid plaque at follow-up, 495 participants developed elevated C-IMT. Compared to the lower NC group, the higher NC group had a significantly increased risk of elevated C-IMT (OR, 1.49; 95% CI, 1.14–1.95; P = 0.003).ConclusionHigher NC was significantly positively correlated with the risk of carotid plaque and elevated C-IMT.     

Hormone replacement therapy use is associated with a lower occurrence of carotid atherosclerotic plaques but not with intima-media thickness progression among postmenopausal women. The vascular aging (EVA) study

BACKGROUND: Information on the impact of hormone replacement therapy (HRT) on carotid atherosclerosis is limited. Moreover, transdermal estrogens have not been investigated. METHODS: We examined association of HRT use with ultrasonographically assessed carotid atherosclerotic plaque occurrence and mean common carotid artery intima-media thickness (CCA-IMT) progression. Within the Vascular Aging (EVA) Study, a community-based cohort, 815 postmenopausal women aged 59-71 have been followed during 4 years. Among these women, 166 had already used HRT. RESULTS: Women who had ever used HRT experienced a lower occurrence of plaques (8.6 versus 19.1%, P=0.003). After adjustment for the main cardiovascular risk factors, odds-ratio for plaque occurrence was 0.41 (95% confidence interval 0.21-0.78, P=0.01) among ever users of HRT compared with never users. When transdermal route of estrogen administration was used, adjusted odds-ratio was 0.66 (95% confidence interval 0.47-0.99, P=0.04). The progression of IMT, which was measured at a plaque-free site and adjusted on initial levels of CCA-IMT did not differ between ever and never users of HRT. It was 0.011 mm per year among ever users and 0.012 mm per year among never users (P=0.61). CONCLUSION: These data suggest that HRT use may prevent the development of atherosclerotic plaques in postmenopausal women, especially when estrogens are administered by transdermal route.     

Absolute and relative changes in carotid intima-media thickness and atherosclerotic plaques during long-term antihypertensive treatment: further results of the European Lacidipine Study on Atherosclerosis (ELSA)

BACKGROUND: In ELSA, a randomized, double-blind trial in 2334 hypertensives, 4-year antihypertensive treatment with lacidipine slowed down progression of carotid atherosclerosis significantly more than atenolol treatment. To avoid bias, the primary outcome was measured blindly at study-end on a randomized sequence of scans, but measurements were limited to the four far walls of common carotids and bifurcations (CBMmax) and to one of each couple of duplicate scans recorded yearly. OBJECTIVES AND METHODS: Secondary outcomes included measurements made on all duplicate scans of both near and far walls, not only of common carotids and bifurcations, but also of internal carotids (12 walls). These measurements were made blindly during the 4-year study, shortly after recording. To avoid possible readers' drift or bias, 250 duplicate baseline scans were re-read at yearly intervals (longitudinal on-line quality control) and a correction factor calculated. RESULTS: Measurements during the 4-year study showed a trend toward decreased values, with the lacidipine effect significantly greater than the atenolol one. A trend toward lower values was also observed in the longitudinal quality control of baseline scans. After applying a correction factor calculated from this longitudinal control, all measurements no longer decreased with time, but significantly increased, with progression being significantly smaller in lacidipine than in atenolol patients. Corrected values were quite similar to those calculated on measurements carried out at study-end. CONCLUSION: The relative benefit of lacidipine over atenolol could be measured precisely by reading scans either during the study or at study-end. However, absolute treatment-related changes (progression versus regression) cannot safely be judged by readings made during a long-term study, unless a longitudinal quality control of readings is performed.     

Common carotid intima-media thickness in growth hormone (GH)-deficient adolescents: a prospective study after GH withdrawal and restarting GH replacement

We prospectively investigated the risk of early atherosclerosis, by classical cardiovascular risk factors and intima-media thickness (IMT) at the common carotid arteries, in 23 adolescents diagnosed as GH deficient (GHD) during childhood and in 23 healthy sex-, age-, and BMI-matched controls. Measurements were performed in all subjects before stopping GH replacement. Because the diagnosis of GHD had been confirmed in 15 of the 23 adolescents, the protocol changed according to the diagnosis as follows: measurements were repeated after 6 months of GH withdrawal and 6 months of GH reinstitution in the 15 with GHD, and after 6 and 12 months of GH withdrawal, measurements were also taken in the eight non-GHD subjects. Serum IGF-I levels were in the normal range for age in all patients before GH withdrawal. When compared with controls, before GH withdrawal, GHD adolescents had reduced high-density lipoprotein cholesterol levels and increased total/high-density lipoprotein cholesterol ratio, fibrinogen, low-density lipoprotein cholesterol, and glucose levels; non-GHD adolescents had increased glucose, insulin, and homeostasis model assessment score. IMT at the common carotid arteries was similar in GHD and controls (0.52 +/- 0.03 vs. 0.55 +/- 0.06 mm; P = 0.23) and was higher in non-GHD than in controls (0.62 +/- 0.03 vs. 0.54 +/- 0.06 mm; P = 0.01). In GHD adolescents, 6 months of GH treatment withdrawal and 6 months of GH treatment reinstitution modified IGF-I levels, lipid profile, and insulin resistance but not IMT or systolic and diastolic peak velocities at the common carotid arteries. In non-GHD subjects, 12 months of GH treatment withdrawal significantly decreased IGF-I levels, IMT (to 0.54 +/- 0.06 mm; P < 0.001 vs. baseline), systolic and diastolic peak velocities, and improved insulin resistance. In conclusion, the discontinuation of GH in confirmed GHD adolescents is not followed by significant alterations of the common carotid arteries, despite the profound negative alterations of the lipid profile. In adolescents who were not confirmed to have GHD, IMT was increased while on GH therapy and normalized when they were taken off of GH.     

MMP-9 microsatellite polymorphism: association with the progression of intima-media thickening and constrictive remodeling of carotid atherosclerotic plaques

Intima-media thickening (IMT) of carotid arteries and constrictive remodeling (CR) of atherosclerotic plaques are vascular pathologic characteristics that precede the onset of vascular events. SMC migration and proliferation are linked both to IMT and CR and are matrix metalloproteinase 9 (MMP-9) dependent. A genetic polymorphism (PM) of MMP-9, a CA (13-27) microsatellite in the promoter region, which accounts for differential expression of MMP-9, could be linked to progression of IMT and CR. Progression of IMT and CR of plaques in carotid arteries were studied in 55 consecutive patients with a 12-18 months follow-up. All patients were genotyped for MMP-9 PM. A positive linear relationship between the number of repeats and the progression of IMT (P=0.028) as well as of CR (P=0.018) was found. The analogous relationship was obtained when only the allele with longer microsatellite was considered. Carriers of more than 20 repeats in one allele showed faster both IMT growth (P=0.045) and stenosis progressions of plaques (P=0.019). In multivariate analysis, age, dyslipidemia, and MMP-9 PM were determinants of IMT progression, while MMP-9 PM was the only one of CR. In conclusion, the high number of CA repeats in MMP-9 promoter is positively correlated with faster IMT and CR progression.     

Evolutionary trends in carotid atherosclerotic plaques: results of a two-year follow-up study using an ultrasound imaging system

A two-year follow-up on 118 atherosclerotic lesions of the extracranial carotid tract observed in 70 patients was carried out using real-time high-resolution echotomography. The following plaque characteristics were monitored: the echogenic patterns (soft, intermediate, hard, and mixed), the surface aspects, and the degree of stenosis. The aim of the study was to evaluate plaque evolution, in relation both to the degree of vessel stenosis produced and to the echostructural characteristics of the lesion. After two years 68% of the lesions remained unchanged while the degree of vessel stenosis increased in 32%; no case of regression was observed. Intrinsic factors appearing to condition an increase in degree of stenosis were "mixed" and "hard" echogenic pattern, an irregular lesion surface, and an initial degree of stenosis of more than 50%. A modification in the echogenic pattern, which generally tended to progress toward more highly reflecting echogenic levels was observed in 27% of the lesions studied.     

血清瘦素与颈动脉内膜-中层厚度关系的探讨

目的：探讨血清瘦素水平与颈动脉内膜—中层厚度(IMT)的相关关系以及瘦素在动脉粥样硬化发生发展中的作用。方法：选择门诊体检正常者56例,分别测定其血清瘦素、空腹血糖、血脂含量,血压及体重指数(BMI)、腰围,同时使用高分辨率超声检测双侧颈动脉 IMT。结果：颈动脉 IMT 与血清瘦素浓度呈显著正相关(男 r=0.41, P＜0.005,女 r=0.44,P＜0.001),与 BMI、腰围、年龄、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、男性收缩压(SBP)及女性舒张压(DBP)呈正相关(r=0.33～0.51,P＜0.05或＜0.001),剔除 BMI 后 IMT 后仍与瘦素呈正相关(r=0.43,P＜0.001)。结论：血清瘦素浓度与颈动脉 IMT 独立相关,提示瘦素可能有加速动脉粥样硬化发展的作用。     

Role of carotid intima-media thickness in assessment of atherosclerosis: an autopsy study

BACKGROUND: The non-invasive technique of measuring carotid artery intima-media thickness has generated considerable interest as a marker of atherosclerosis, particularly in predicting clinical coronary events and coronary artery disease. In the present study, a postmortem comparative analysis of intima-media thickness of carotid artery with coronary artery atherosclerosis has been carried out. To date no such morphological tissue studies are available from our country. METHODS AND RESULTS: Right and left common carotid arteries with their branches were removed at postmortem in 40 cases with history of diabetes, hypertension or both. Intima-media thickness was measured and compared with coronary artery atherosclerosis. There were 10 control postmortem cases without history of diabetes or hypertension. Common carotid artery and internal carotid artery intima-media thickness were found to be good predictors of coronary events. There was also significant correlation (by Pearson's correlation formula) between the carotid artery intima-media thickness and the percentage of block in the coronary arteries. CONCLUSIONS: Internal carotid artery along with common carotid artery intima-media thickness measurement is a good predictor of coronary artery disease. However, carotid artery intima-media thickness has no bearing on the status of collateral circulation of the coronary arteries.     

Plasma level of asymmetric dimethylarginine (ADMA) as a predictor of carotid intima-media thickness progression: six-year prospective study using carotid ultrasonography

This study was designed to determine the relationship between plasma asymmetric dimethylarginine (ADMA) and the development of carotid atherosclerosis. Cross-sectional studies have revealed that plasma ADMA concentration is correlated with the intima-media thickness (IMT) of the carotid artery, but no prospective studies have appeared. Therefore we prospectively investigated whether or not plasma ADMA level can predict IMT progression. In a community-based cohort, we enrolled 712 subjects who were over 40 years old and who had no apparent cardiovascular diseases according to high-resolution carotid ultrasonography. Blood chemistries including ADMA were measured at baseline. In 575 subjects, IMT was re-measured 6 years later. The value of baseline ADMA for predicting IMT changes was investigated by multivariable analysis. At baseline, there was a significant (beta=0.321; p<0.001) relationship between IMT and ADMA levels. Multiple linear regression analysis revealed that baseline ADMA (beta=0.241; p<0.01) was the only predictor of IMT progression after adjustments for age, sex, baseline IMT, and four major risk factors (hypertension, hypercholesterolemia, diabetes mellitus, and smoking) plus hyperuricacidemia. Plasma ADMA was a predictor of carotid IMT progression.     

Plasma levels of asymmetric dimethylarginine (ADMA) are related to intima-media thickness of the carotid artery: an epidemiological study

Asymmetric dimethylarginine (ADMA) is a circulating endogenous nitric oxide (NO) synthase inhibitor. It has been reported that plasma levels of ADMA are related to intima-media thickness (IMT) in small numbers. We investigated this issue in a large number of subjects without overt cerebro-cardiovascular diseases. A total of 712 subjects (305 men and 407 women; age, 62.6+/-11.2 years) received a health examination in 1999 in a farming community. We measured blood pressure (BP), blood chemistries, and fasting plasma total ADMA levels. IMT of the common carotid artery was determined with the use of duplex ultrasonography as an index of atherosclerosis. Uni- and multi-variate analyses for determinants of IMT were performed. For the total population, the mean ADMA level was 0.50 micromol/l. By the use of multiple stepwise regression analysis, IMT was significantly associated with ADMA (p<0.01), age (p<0.001), and systolic BP (p<0.001). Furthermore, when IMT was analyzed across the ADMA tertiles after adjustments for age, sex, and other confounders, analysis of co-variance showed a significant (p<0.001) and linear association between IMT and ADMA levels. In conclusion, our study indicates that plasma level of ADMA is a strong and independent determinant of IMT of the carotid artery in the large number of subjects without overt cerebro-cardiovascular diseases.     

Baseline reproducibility of B-mode ultrasonic measurement of carotid artery intima-media thickness: the European Lacidipine Study on Atherosclerosis (ELSA)

BACKGROUND AND OBJECTIVE: The European Lacidipine Study of Atherosclerosis (ELSA) is a prospective, randomized, double-blind, multi-national interventional trial to determine the effect of four-year treatment using the calcium antagonist lacidipine versus the beta-blocker atenolol on the progression of carotid atherosclerosis in 2259 asymptomatic hypertensive patients. B-mode ultrasound is used to measure the primary and secondary endpoints including the mean maximum intima-media thickness (IMT) of the carotid bifurcations and the common carotid arteries (CBM(max)), the mean maximum IMT of 12 standard carotid sites (M(max)) and the overall maximum IMT (T(max)). This paper reports the cross-sectional reproducibility of ultrasound measurements at baseline. METHOD: To evaluate measurement reliability, each patient is scanned twice at baseline and again at four annual visits, with 80% of the replicate scans performed by the same sonographer and 20% by a different sonographer; 50% of the replicate scans are read by the same reader and the other 50% by different readers. RESULTS: The overall coefficient of reliability (R) was 0.859 for CBM(max), 0.872 for M(max) and 0.794 for T(max). The reliability for CBM(max) was stable during the 1 3/4-year baseline period (R = 0.848 to 0.953) and was uniform among the 23 field centres (R = 0.798 to 0.926). Intra- and inter-reader reliability were 0.915 and 0.872 respectively, and intra-sonographer reliability was 0.866. CONCLUSION: The results demonstrate that by implementing standardized protocols and strict quality control procedures, highly reliable ultrasonic measurements of carotid artery IMT can be achieved in large multi-national trials.