Circulating oxidized low-density lipoprotein is associated with echolucent plaques in the femoral artery independently of hsCRP in 61-year-old men

OBJECTIVES: The aim of the study was to test the hypothesis that circulating markers of inflammation (high-sensitive C-reactive protein, hsCRP) and oxidative modification of lipids (oxidized low-density lipoprotein, oxLDL) were associated with the occurrence of echolucent rather than echogenic femoral artery plaques in a cross-sectional population based cohort of 513, 61-year-old men. BACKGROUND: The relationships between circulating oxLDL, hsCRP and the occurrence of echolucent plaques in the femoral artery have not previously been investigated. METHODS: The levels of circulating oxLDL and hsCRP were determined in plasma by ELISA. Plaque occurrence, size and echogenicity were measured by B-mode ultrasound in the right femoral artery. Assessment of plaque echogenicity was based on the classification (grades 1-4) proposed by Gray-Weale et al. RESULTS: A higher frequency of echolucent femoral plaques was observed in subjects with the metabolic syndrome and current smokers (p=0.01 and p<0.001, respectively) as well as with increasing levels of oxLDL and hsCRP (p=0.002 and p=0.005, respectively). In a multiple logistic regression analysis oxLDL and current smokers turned out to be independent associated with the presence of echolucent femoral artery plaques. CONCLUSIONS: The results of the present study support our hypothesis that circulating oxLDL is a marker of an unstable echolucent plaque phenotype in the femoral artery in man.     

Plasma levels of granzyme B are increased in patients with lipid-rich carotid plaques as determined by echogenicity

Increased echolucency of carotid plaques is associated with an increased risk of ischemic stroke. Inflammation and apoptosis of vascular smooth muscle cells in the arterial wall are involved in the atherosclerotic process and destabilization of the plaque. Granzyme B (GrB) is a key mediator of T cell-mediated cytotoxicity, and we therefore hypothesized that this protease could distinguish echolucent from other plaques. Ultrasound-determined echolucency of atherosclerotic plaques was assessed prior to carotid endarterectomy/angioplasty in 57 consecutively recruited patients with high-grade internal carotid stenosis. Plasma levels of GrB were measured by enzyme immunoassay prior to surgery. Patients with carotid atherosclerosis had significantly higher plasma levels of GrB compared to healthy controls (n=16) (p<0.01), with particularly high levels in those with an echolucent lesion. While there were no differences in traditional cardiovascular risk factors or CRP between those with echolucent (n=16) and those with echogenic/heterogeneous (n=41) plaques, the echolucent group had markedly raised plasma levels of GrB (p<0.01). Patients with high levels of circulating granzyme B also had more ischemic lesions on cerebral MRI prior to surgery. Raised plasma levels of GrB in echolucent carotid plaques with increased frequency of cerebrovascular events suggest that GrB may be a marker of plaque instability.     

Haemoglobin A1c is associated with carotid intima-media thickness in a Chinese population

Background The association between haemoglobin A1c (HbA1c) levels and subclinical atherosclerosis in carotid arteries in Chinese populations is unknown. Aim, design and methods The objective of this study was to investigate this relationship and evaluate the ability of HbA1c levels to predict carotid atherosclerosis in a Chinese population. This was a cross‐sectional study, which included 541 subjects without known diabetes (Taiwan Lifestyle Study). About 67 (9·2%) subjects were newly diagnosed with diabetes during the study. Carotid intima–media thickness (IMT) and the presence of carotid plaques were determined using ultrasonography. Results The HbA1c level in all subjects was positively correlated with carotid IMT (β = 0·018, P = 0·03) after being adjusted for age, gender, smoking, low‐density lipoprotein cholesterol level, hypertension and body mass index. HbA1c level was higher in subjects with plaques in carotid arteries (P = 0·01). There was a positive and linear relationship between HbA1c levels and the probability of having plaques, thickened carotid IMT or both (P for all comparisons, <0·05). The ability of HbA1c levels to predict thickened carotid IMT or the presence of plaques was only modest {the optimal cutoff of HbA1c level [5·7%] was determined from the receiver operating characteristic (ROC) curve (sensitivity = 67%, specificity = 61%) and the area under the ROC curve [0·666]}. Conclusions Thus, HbA1c level is associated with subclinical atherosclerosis in carotid arteries in a Chinese population. The relationship is linear without an inflection point. However, HbA1c criterion is not a useful marker for the identification of subclinical atherosclerosis.     

The role of carotid plaque vulnerability and inflammation in the pathogenesis of acute ischemic stroke

BACKGROUND: Increasing evidences show that disruption of carotid plaque followed by arterio-arterial thromboembolism is an important mechanism in the generation of ischemic stroke. Inflammatory mechanisms play a key role in transforming structurally vulnerable plaques into functionally unstable ones. The purpose of the present study is to evaluate the roles of carotid plaque vulnerability and inflammation in the pathogenesis of acute ischemic stroke. METHODS: Fifty-two patients with acute ischemic stroke affecting the anterior circulation (stroke group) and 44 with asymptomatic carotid stenosis (asymptomatic group) were investigated. Duplex ultrasonography was used to evaluate the characteristics of carotid plaque and grading the degree of carotid stenosis. Plaque echogenicity was assessed as echolucent, predominantly echolucent, predominantly echogenic, or echogenic. Plaque surface was classified as smooth, irregular, or ulcerated. All subjects had duplex-determined 50% to 99% carotid stenosis. Serum levels of matrix metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinases (TIMP-1), soluble CD40 ligand (sCD40L) and high-sensitivity C-reactive protein (hsCRP) were measured. RESULTS: Plaques in the stroke group were echolucent or predominantly echolucent, whereas those of the asymptomatic group were predominantly echogenic or echogenic plaques (P<0.05). Irregular and ulcerated plaques were frequently found in stroke patients, while smooth plaques were frequently detected in asymptomatic patients (P<0.05). Serum levels of MMP-9, sCD40L, hsCRP were higher in stroke than in asymptomatic patients. By contrast, serum TIMP-1 levels were significantly higher in the asymptomatic than in the stroke group. CONCLUSIONS: The results suggest that inflammation plays a crucial role in carotid plaque vulnerability and, together with carotid plaque morphology, in the pathogenesis of acute ischemic stroke.     

高血压合并2型糖尿病患者颈动脉硬化与基质金属蛋白酶-9和脂蛋白(a)的关系

目的探讨基质金属蛋白酶-9(MMP-9)及脂蛋白-a[LP(a)]与高血压合并2型糖尿病(DM)患者颈动脉粥样硬化的关系。方法单纯高血压患者82例采用彩色超声仪进行颈动脉超声检查,检测颈动脉内膜-中膜厚度(IMT),采用ELISA法测定血清中MMP-9及LP(a)等指标;并以同样的方法观察高血压合并2型DM的患者86例辛伐他汀(10mg/d.次)治疗12周前后的上述指标。结果高血压合并2型DM的患者IMT值、斑块发生率、颈动脉斑块积分及MMP-9和LP(a)等值明显高于单纯高血压患者[IMT:(1.29±0.10vs0.96±0.15)mm;斑块发生率:(79.8%vs22.6%);颈动脉斑块积分:(6.0±0.4vs1.7±0.7);MMP-9:(649.1±51.0vs213.2±23.3)μg/L;LP(a):(2132.0±342.2vs765.4±154.1)mg/L(P<0.01)]。MMP-9及LP(a)与高血压合并2型DM的患者IMT值、颈动脉斑块发生率、斑块积分呈正相关,r值分别为(0.80、0.74、0.84、0.76、0.78、0.80,P<0.05)。经辛伐他汀治疗12周,MMP-9和LP(a)下降,颈动脉斑块有所消退。结论MMP-9及LP(a)在高血压合并2型糖尿病患者颈动脉粥样硬化发生发展过程中可能起重要作用。经辛伐他汀治疗,在MMP-9及LP(a)下降的同时颈动脉斑块有所消退。     

老年人动脉弹性与颈动脉斑块超声特征相关性研究

目的探讨老年人动脉弹性与颈动脉斑块不同超声分型的关系。方法选定北京军队干休所的721例老年人（年龄≥60岁）,填写调查表,行颈动脉超声多普勒检测颈总动脉内中膜厚度（IMT）、颈内外动脉及颈总动脉斑块情况,根据颈动脉斑块的不同回声强度,将颈动脉斑块分为硬斑组及软斑组,半定量估计颈动脉粥样硬化斑块等级。采用全自动动脉硬化测定仪（日本Colin公司生产VP-1000）同步记录左右侧臂踝脉搏波传导速度（PWV）作为反映大动脉弹性的指标。应用统计学方法探讨老年人动脉弹性与颈动脉斑块不同超声分型之间的关系。结果收缩压、PWV在硬斑组较软斑组明显升高,血总胆固醇、血甘油三酯在软斑块组明显增高,两组之间存在显著差异,而其他心血管病危险因素在两组间无差别。半定量法估计颈动脉斑块等级,PWV在硬斑组中随着斑块严重程度而增加,三组之间具有显著性差异,而软斑组未显示同样的差别。结论PWV与硬斑密切相关,提示动脉弹性减退与硬斑形成可能具有相似的病理发展过程。     

Oxidized low-density lipoprotein in plasma is a prognostic marker of subclinical atherosclerosis development in clinically healthy men

OBJECTIVE: To investigate the association between plasma oxidized low-density lipoprotein (OxLDL) and the progress of clinically silent atherosclerosis, as measured by ultrasound in the carotid arteries. DESIGN: Prospective, observational study with more than 3 years of follow-up. SETTING: One-centre study at university hospital. MATERIAL AND METHODS: The subjects (n = 326) were obtained by stratified sampling from a population sample of men who were 58 years old at baseline. Carotid artery intima-media thickness (IMT) was measured bilaterally by high-resolution B-mode ultrasound at baseline and after follow-up. Plasma OxLDL cholesterol concentrations and conventional cardiovascular risk factors were measured at study entry. Automated measurements of IMT were performed. Plaque occurrence and size were assessed (plaque status). Plasma OxLDL at entry was measured by a specific monoclonal antibody, mAb-4E6. RESULTS: OxLDL at entry, but not LDL cholesterol, was associated with the number and size of plaques at follow-up (P = 0.008), also after adjustment for plaque status at entry (P = 0.033). The plasma OxLDL concentration at entry was associated with change in carotid artery IMT (r = 0.17; P = 0.002) and in a stepwise multiple regression analysis this association remained after adjustment for other cardiovascular risk factors (P = 0.005). CONCLUSIONS: These results provide new information, supporting the concept that circulating OxLDL was associated with the silent phase of atherosclerosis progression in clinically healthy men independently of conventional risk factors.     

Release of protein as well as activity of MMP-9 from unstable atherosclerotic plaques during percutaneous coronary intervention

Abstract. Robertson L, Grip L, Mattsson Hultén L, Hulthe J, Wiklund O. (Göteborg University, Göteborg; Borås Hospital, Borås; and AstraZeneca, Mölndal, Sweden). Release of protein as well as activity of MMP‐9 from unstable atherosclerotic plaques during percutaneous coronary intervention. J Intern Med 2007; 262 : 659–667. Objectives. Few studies have investigated the composition of unstable coronary plaques in vivo in humans. The aims of this study were to investigate if substances released from plaques during percutaneous coronary intervention (PCI) under distal protection could give information about plaque composition and also indicate possible biomarkers in plasma that may be used to identify patients at risk. Methods and results. Twenty patients with acute coronary syndromes undergoing PCI with distal protection were included. Plasma samples were taken before, during, and after the PCI in the aortic root, locally in the culprit vessel and intravenously. Plasma was analysed for possible markers of plaque instability. During PCI, local increases were observed for matrix metalloproteinase 9 (MMP‐9), protein (P < 0.001) as well as activity (P < 0.001), interleukin 6 (IL‐6; P < 0.01) and oxidized low‐density lipoprotein (oxLDL; P = 0.01) in the culprit coronary artery. A systemic inflammatory response was also seen with increased levels of IL‐10, MMP‐3, serum amyloid A and C‐reactive protein, but with no increase in MMP‐9. Conclusions. Our study shows that local sampling of blood under distal protection may be used to analyse coronary plaques and to identify biomarkers for unstable plaques. Our results suggest that MMP‐9 is a potential biomarker, and that IL‐6, MMP9 and possibly oxLDL are released from plaques.     

Serum levels of matrix metalloproteinase‐9, tissue inhibitors of metalloproteinase‐1 and their ratio are associated with impaired lung function in the elderly: A population‐based study

Background and objective: Matrix metalloproteinases (MMP) and their inhibitors, tissue inhibitors of metalloproteinases (TIMP), regulate homeostasis and turnover of the extra cellular matrix. The aim of this study was to investigate the associations of serum MMP‐9 and TIMP‐1 with lung function. Methods: Spirometry was performed in a population‐based sample of 888 subjects aged 70 years. Serum MMP‐9 and TIMP‐1 concentrations were measured by ELISA. Results: Lower FEV₁ values were associated with higher serum levels of MMP‐9 (P = 0.001) and TIMP‐1 (P < 0.001), and a higher ratio of MMP‐9 to TIMP‐1 (P = 0.02). These associations were significant after adjustment for gender, weight, height, BMI, current smoking, pack years of smoking and the time for which samples were frozen. After stratification for gender, the associations between FEV₁ and MMP‐9, TIMP‐1, and their ratio, were significant in men but not in women. Conclusions: Lower FEV₁ was significantly but weakly associated with higher serum levels of MMP‐9, TIMP‐1 and a higher MMP‐9/TIMP‐1 ratio. This association was stronger in men than in women, suggesting a possible role for extracellular matrix remodelling in the development of impaired lung function. These associations may also partly explain the association between low FEV₁ and cardiovascular disease.     

Elevated Circulating Osteoprotegerin Levels in the Plasma of Hemodialyzed Patients With Severe Artery Calcification

We studied the correlations between circulating osteoprotegerin (OPG) level and radial artery calcification (RAC) assessed histologically and carotid artery intima‐media thickness (CCA‐IMT). Moreover, we studied the relationship between OPG levels and all‐cause and cardiovascular (CV) mortality during a 5‐year observation period. The study comprised 59 CKD patients (36 hemodialyzed (HD), 23 predialysis). The biochemical parameters included: creatinine, calcium, phosphate, intact parathormone, C‐reactive protein, interleukin‐6, tumor necrosis factor receptor II (TNFRII), transforming growth factor‐β, hepatocyte growth factor, fibroblast growth factor 23, osteonectin (ON), osteopontin, osteoprotegerin, and osteocalcin. CCA‐IMT and the presence of atherosclerotic plaques was assessed by ultrasound. Fragments of radial artery obtained during creation of HD access were prepared for microscopy and stained for calcifications with alizarin red. RAC was detected in 34 patients (58%). In multiple regression adjusted for dialysis status, TNFRII, ON and Framingham risk score (FRS) were identified as the independent predictors of OPG. Serum OPG above the median value of 7.55 pmol/L significantly predicted the presence of RAC in simple logistic regression (OR 5.33; 95%CI 1.39–20.4; P = 0.012) and in multiple logistic regression adjusted for FRS, dialysis status and CCA‐IMT values (OR 6.56; 95%CI 1.06–40.6; P = 0.036). OPG levels above the median were associated with higher CCA‐IMT values (1.02 ± 0.10 vs. 0.86 ± 0.13; P < 0.001) and predicted the presence of atherosclerotic plaques in carotid artery (OR 14.4; 95%CI 2.84–72.9; P < 0.001), independently of FRS, dialysis status and RAC. In this study, elevated serum OPG levels correlated with higher CCA‐IMT, the presence of atherosclerotic plaques and the severity of the RAC independently of each other. During follow‐up, 25 patients (42%) died, including 21 due to CV causes. In multiple Cox regression, OPG above the median predicted overall survival independently of dialysis status, Framingham risk score, CCA‐IMT above the median value, and the presence of atherosclerotic plaques in CCA, but not independently of RAC. We postulate that circulating OPG may play a dual role as a marker for both medial arterial calcification and atherosclerosis, hence it seems to be a valuable tool for assessing CV risk in patients with CKD. OPG might be an early indicator of all‐cause mortality in CKD patients with advanced medial arterial calcification.     

Carotid and femoral atherosclerosis, cardiovascular risk factors and C-reactive protein in relation to smokeless tobacco use or smoking in 58-year-old men

Objectives. To examine the associations between smokeless tobacco use, smoking, cardiovascular risk factors, inflammation and ultrasound-assessed measures of atherosclerosis in the carotid and femoral arteries. Subjects. The study was performed in a population-based sample of clinically healthy men (n = 391) all 58 years old. Exclusion criteria were cardiovascular or other clinically overt diseases or continuous medication with cardiovascular drugs. Methods. The habits of smoking and oral moist snuff use were assessed by questionnaires. C-reactive protein (CRP) was assessed by high sensitive enzyme-linked immunosorbent assay (ELISA). Intima-media thickness (IMT) in the carotid bulb, the common carotid artery and the common femoral artery and plaque occurrence were measured by ultrasound. Results. The use of oral moist snuff was associated with serum triglycerides and waist-hip ratio (WHR), but not with CRP or ultrasound-assessed measures of subclinical atherosclerosis. Smoking, on the other hand, was associated with CRP, the components in the metabolic syndrome and IMT as well as plaques in the carotid and femoral arteries. In comparison to never-smokers the current smokers had higher values of WHR, triglycerides, C-reactive protein and IMT in carotid bulb and femoral artery. Ex-smokers were in general more obese and had a femoral IMT that was in-between that of never-smokers and current smokers. Conclusions. Tobacco smoking, but not oral moist snuff use, was associated with carotid and femoral artery IMT, and increased levels of CRP. Current smoking was also associated with abdominal obesity. Ex-smokers though, are generally more obese. Smoking was also associated with hyperinsulinaemia, dyslipidaemia and high blood pressure, i.e. the metabolic syndrome. The inhaled smoke from the combustion of tobacco seems to be an important aetiological factor in the atherosclerotic process.     

A myocardial infarction genetic risk score is associated with markers of carotid atherosclerosis

Abstract. Hamrefors V, Hedblad B, Engström G, Almgren P, Sjögren M, Melander O (Lund University, Malmö, Sweden). A myocardial infarction genetic risk score is associated with markers of carotid atherosclerosis. J Intern Med 2012; 271 : 271–281. Objective. To assess whether or not a genetic risk score that was previously shown to be associated with myocardial infarction (MI) and coronary artery disease (CAD) is also associated with markers of carotid atherosclerosis. Design. A total of 4022 middle‐aged subjects from the general Swedish population were genotyped and individually assigned a genetic risk score based on 13 single‐nucleotide polymorphisms (SNPs), previously associated with MI and CAD. The genetic score (Score‐MI) was then related to carotid bulb intima–media thickness (IMT), common carotid artery (CCA) IMT and to the occurrence of carotid plaques in the study population. Results. Score‐MI was associated with IMT of the bulb (P < 0.001) and the CCA (P < 0.001) in unadjusted analyses, and with IMT of the bulb after adjustment for cardiovascular risk factors (P = 0.003). The effect size of Score‐MI on IMT of the bulb was similar to that of LDL cholesterol. After adjustment for cardiovascular risk factors, Score‐MI was also associated with the occurrence of carotid plaques (odds ratio per quintile of Score‐MI = 1.11; 95% confidence interval 1.04–1.18; P = 0.001). In addition to SNPs with known effects on LDL levels, Score‐MI showed nominal associations with increasing systolic blood pressure and decreasing C‐reactive protein levels. Conclusions. This genetic risk score was independently associated with carotid bulb IMT and carotid plaques, providing evidence of an association with early markers of atherosclerosis. This might imply that the genetic MI risk conferred by the score is related to early atherosclerosis and that the risk score may identify at an early stage candidates at risk of developing intermediate phenotypes of atherosclerosis. Further studies should test whether or not assessing the genetic score could be valuable for early treatment decisions in these subjects.     

Serum Homocysteine,MTHFR Gene Polymorphism,and Carotid Intimal-Medial Thickness in NIDDM Subjects

We assessed the contribution of serum homocysteine levels, an independent risk factor for vascular disease, and of the methylenetetrahydrofolate reductase (MTHFR) C677T mutation to the variability of carotid intimal-medial thickness (IMT) in patients with non–insulin-dependent diabetes mellitus (NIDDM). Ninety-five patients (33 males and 62 females, mean age 53 ± 10 years) without nephropathy or other vascular complications were enrolled. Fasting total serum homocysteine and other biochemical analytes were measured. The MTHFR polymorphism was determined by the polymerase chain reaction. Common carotid IMT and plaques or stenoses in the carotid district were measured by ultrasonography. Serum total homocysteine concentrations were higher in subjects with the mutant (Val/Val) genotype than in those with the Ala/Val plus Ala/Ala genotypes (P = 0.02). On univariate analysis, carotid IMT was significantly associated with age, body mass index (BMI), systolic blood pressure, and total cholesterolemia. No significant association was found between IMT and serum homocysteine or the MTHFR polymorphism, although a slightly greater IMT was observed in the homozygous Val genotypes. On multiple regression analysis, only age and BMI were independently associated with IMT and explained about 40% of IMT variability. The results did not change when the analysis was restricted to the subgroups with or without atherosclerotic plaques in the carotid district. In 95 Italian NIDDM patients without nephropathy, neither basal levels of serum total homocysteine nor the MTHFR C677T polymorphism predicted significant changes in common carotid intimal-medial thickness.     

Plasminogen activator inhibitor-1 and carotid intima-media thickening in patients with newly detected primary hypertension

OBJECTIVE: To investigate the correlation between ultrasonographically evaluated intima-media thickness (IMT) of common carotid artery (CCA) and cardiovascular risk factors for subjects with newly detected, uncomplicated and untreated primary hypertension. METHODS: The study population consisted of 200 subjects (123 men and 77 women, aged 46+/-7.5 years). Blood pressure was measured in the clinical setting and by 24 h noninvasive ambulatory monitoring. Fasting levels of blood glucose, plasma lipids and lipoproteins, fibrinogen and plasminogen activator inhibitor (PAI)-1 were measured. Ultrasound examination included measurement of far-wall intima-media complex of CCA and morphologic evaluation of occurrence of plaques in carotid and femoral bifurcations. RESULTS: The prevalence of greater than normal IMT (mean IMT > or =0.80 mm) was 22%. Significant univariate correlations to the dichotomy between normal and greater than normal mean IMT were detected for age, smoking, level of LDL cholesterol, level of PAI-1 and total ultrasonographic score. Multivariate logistic regression analysis confirmed the associations between greater than normal mean IMT and plasma concentrations of LDL cholesterol and PAI-1 as well as total ultrasonographic score. CONCLUSION: Greater than normal IMT of CCA was more strictly related to other cardiovascular risk factors than it was to blood pressure and was strongly associated with the occurrence of atherosclerotic plaques in carotid and femoral arteries. The role of PAI-1 in intima-media thickening that is emerging suggests that fibrinolytic balance is an important determinant of vessel-wall homeostasis in hypertensive patients.     

Serum osteoprotegerin is inversely associated with carotid plaque echogenicity in humans

Osteoprotegerin (OPG) is a member of the tumour necrosis factor superfamily involved in the regulation of bone metabolism and vascular calcification. High serum values of OPG are associated with cardiovascular disease in humans. The purpose was to investigate serum OPG levels in subclinical carotid atherosclerosis and the relation between OPG levels and plaque morphology. OPG levels were compared in 29 persons with echogenic carotid plaques, 30 persons with echolucent plaques and 41 persons without carotid plaques, all recruited from a population health study. Computerized assessment of plaque echogenicity was done by use of the gray scale median (GSM). Participants with echogenic carotid plaques had lower serum OPG level (1.23 ng/ml; 1.02-1.48) (geometric mean; 95% CI) than persons with echolucent plaques (1.76 ng/ml; 1.46-2.14) and those without plaques (1.89 ng/ml; 1.60-2.21). OPG and PTH were independently related to GSM. A significant trend for decrease in GSM across quartiles of OPG was found (p=0.003) which remained significant even after adjustment for PTH and smoking. The present study demonstrates lower serum OPG levels in persons with subclinical echogenic carotid plaques and identified an inverse relation between serum OPG and plaque echogenicity. The findings support the concept that OPG may play an important role in arterial calcification.     

Interleukin 6 is associated with subclinical atherosclerosis: a link with soluble intercellular adhesion molecule 1

BACKGROUND: Among the markers of inflammation, a cytokine, interleukin (IL)-6, promotes the expression of intercellular adhesion molecule 1 (ICAM-1), C-reactive protein (CRP) synthesis, and leads to a series of procoagulant actions with potential major implications on the progression of atherosclerosis. AIM OF THE STUDY: To analyse in a population-based study, the relationship between IL-6 and atherosclerotic lesions and the role of serum ICAM-1 and CRP on this relationship. POPULATION: Among 1015 individuals randomly recruited between 1995 and 1997 in Haute-Garonne, a French region with a low cardiovascular risk, 953 subjects with complete data for all measurements were analysed. Common carotid intima-media thickness (IMT) and the presence of plaques in the carotid and femoral arteries were assessed by ultrasonography. RESULTS: Quartiles of IL-6, serum ICAM-1 and CRP were positively associated with plaques and IMT. After adjustment for traditional risk factors, IL-6 (P < 0.001) and serum ICAM-1 (P < 0.002) remained positively associated with plaques but not CRP (P = 0.20). Neither IL-6, nor serum ICAM-1, nor CRP were independently associated with IMT. When serum ICAM-1 was entered into the model in addition to traditional risk factors and IL-6, the percentage of variance in the number of plaques explained by the model did not increase significantly. CONCLUSION: IL-6 levels are associated with subclinical atherosclerotic lesions independently of traditional risk factors; the influence of IL-6 on ICAM-1 secretion may play a role in this association. These results argue the interest of IL-6 in the stratification of cardiovascular risk.     

老年男性高血压患者睾酮水平与颈动脉内膜-中层厚度的相关性研究

目的探讨老年男性高血压患者的血浆睾酮（T）水平与颈动脉内膜-中层厚度（IMT）的相关性。方法选取90例老年男性原发性高血压患者,根据有无颈动脉粥样硬化斑块,分为有斑块组（n=56）和无斑块组（n=34）;另选取80例健康老年男性作为对照组。检测所有受试对象的血浆T水平、颈动脉IMT,分析指标间的相关性。结果有斑块组收缩压（SBP）、舒张压（DBP）、IMT水平均高于无斑块组和对照组（P〈0.05或P〈0.01）,而血浆T水平均低于这2组（P〈0.05或P〈0.01）;老年男性高血压患者血压、血浆T水平与颈动脉IMT之间均具有相关性,血浆T水平与SBP、DBP、IMT均呈负相关（P〈0.01）。结论老年男性高血压患者的T水平与动脉粥样硬化程度呈负性相关,其血浆T水平可为疾病评估、激素替代治疗等提供理论参考依据。     

Low testosterone levels are associated with carotid atherosclerosis in men

Objective. To study the relationship between endogenous sex hormone levels and intima‐media thickness (IMT) of the carotid artery measured by ultrasonography. Design. Population‐based cross‐sectional study. Methods. Sex hormone levels measured by immunoassay, anthropometric measurements and IMT was studied in 1482 men aged 25–84 years participating in the 1994–1995 Tromsø study. The data were analysed with partial correlation, multiple linear regression and logistic regression analysis. Results. Linear regression models showed that total testosterone and sex hormone‐binding globulin levels, but not calculated free testosterone, serum oestradiol or dehydroepiandrosterone sulphate levels were inversely associated with the age‐adjusted IMT (P = 0.008 and P < 0.001 respectively). These associations were independent of smoking, physical activity, blood pressure and lipid levels, but were not independent of body mass index (BMI). Excluding men with cardiovascular disease (CVD) did not materially change these results. In a logistic regression model adjusted for the confounding effect of CVD risk factors, men with testosterone levels in the lowest quintile (<9.0 nmol L^?1) had an independent OR = 1.51 (P = 0.015) of being in the highest IMT quintile. Conclusions. We found an inverse association between total testosterone levels and IMT of the carotid artery in men that was present also after excluding men with CVD, but was not independent of BMI. The clinical relevance of this, however, is uncertain and needs to be investigated in a clinical setting.     

Simultaneous up-regulation of matrix metalloproteinases 1, 2, 3, 7, 8, 9 and tissue inhibitors of metalloproteinases 1, 4 in serum of patients with chronic obstructive pulmonary disease

Background and objective: Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) have been implicated in chronic obstructive pulmonary disease (COPD) pathogenesis. However, the majority of studies have focused on single MMP, and there is limited information on parallel expression of MMP and their antagonists TIMP. We, therefore, investigated the serum profile of MMP 1–3, 7–9, 12 and 13, and TIMP 1–4 in COPD patients. Methods: Serum MMP 1–3, 7–9, 12 and 13, and TIMP 1–4 were measured in 74 COPD patients and 20 control subjects by multiple microsphere technology. Results: MMP 1–3 and MMP 7–9 were elevated in COPD patients compared with control subjects (P= 0.001–0.043). The increased concentrations of MMP 1, 8 and 9 paralleled GOLD stage (P= 0.002–0.007). TIMP 1 and 4 concentrations were elevated in COPD (P < 0.001). MMP 1, 8 and 9, and TIMP 1 and 4 serum levels in COPD non‐smokers were higher than in control non‐smokers (P= 0.002–0.025). MMP 12 and 13 levels were undetectable in our serum samples. Conclusions: This study provides further evidence for increased MMP 1, 7–9, and TIMP 1 serum levels in COPD, and demonstrates for the first time serum elevation of MMP 2 and 3, and TIMP 4. The finding that circulating TIMP 4 levels are increased in COPD and the observed relationship between serum levels of MMP 1, 8 and 9, and GOLD stage requires verification in an expanded patient cohort.     

Echogenic carotid plaques are associated with aortic arterial stiffness in subjects with subclinical carotid atherosclerosis

A better understanding of the interrelationships between the structure and function of the large arteries would lead to optimize cardiovascular disease prevention strategies. In this study, we investigated the relationships of aortic arterial stiffness assessed by carotid-femoral pulse-wave velocity (PWV), with carotid plaque echogenicity assessed by B-mode ultrasound. We analyzed 561 subjects (without coronary heart disease or stroke) who were volunteers for free health examinations (age, 58.3+/-10.8 years; 32.6% women). Extracranial carotid plaque echogenicity was graded from 1 (plaque appearing black or almost black) to 4 (plaque appearing white or almost white) according to the Gray-Weale classification. Plaques of grades 1 and 2 were defined as echolucent plaques, and plaques of grades 3 and 4 were defined as echogenic plaques. Fifty-one subjects (9.1%) had echolucent carotid plaques, 109 (19.4%) had echogenic plaques, and 401 (71.5%) had no plaques. Subjects with echogenic plaques had higher PWV mean (12.9+/-2.8 m/s) compared with those without plaques (11.1+/-2.3 m/s, P<0.001) and compared with those with echolucent plaques (11.3+/-2.3 m/s, P<0.01). The PWV means in subjects without plaques and those with echolucent plaques were similar and not statistically different (P=0.55). When multivariate adjustment for major known cardiovascular risk factors was performed, these results were not markedly modified. Similar patterns of results were also observed in many subgroups according to age, gender, and hypertensive status. This study provides the first evidence that echogenic but not echolucent carotid plaques are associated with aortic arterial stiffness. This association applies to individuals with normal blood pressure and those with elevated blood pressure. Assessment of the joint and interaction effects of plaque morphology and arterial stiffness on the occurrence of cardiovascular events would permit a better identification of high-risk subjects.