Plasma-induced endothelial activation associated with incident atherosclerosis: prospective results from the Bruneck Study

BACKGROUND: Whether systemic inflammation is an epiphenomenon of atherosclerosis or whether it is part of the atherosclerosis causal pathway requires further study. DESIGN: As part of a prospective population survey on the course and aetiology of atherosclerosis, we investigated the effects of plasma on the endothelial monolayers inducing activation for leukocyte transmigration. METHODS: An age- and sex-stratified random sample of inhabitants of Bruneck (Italy) with and without atherosclerotic disease aged 50-69 years was selected. Carotid arteries were evaluated by duplex sonography at baseline (1990). Carotid arteries were re-evaluated for the development of new plaques 5 years later (1995). Frozen plasma samples from baseline were available for a random sample of 152 men. Monolayers of endothelial cells cultured in micropore filter insets were pre-treated with plasma, then normal human neutrophils were added to the endothelial cells and subsequent transmigration through the monolayers and micropore filters was measured. RESULTS: The endothelial monolayers were activated for transmigration of leukocytes more potently by plasma from participants with carotid artery plaques than participants without it. Increased endothelial activation with plasma at baseline was associated with the development of new atherosclerotic lesions during a period of 5 years. CONCLUSIONS: Plasma from individuals with prevalent atherosclerosis of the carotid arteries activates the endothelium for leukocyte transmigration, suggesting the presence of systemic pro-inflammatory mediators. In an epidemiological survey, follow-up data on new lesion formation after 5 years indicated that plasma-mediated endothelium activation for interaction with leukocytes precedes the development of atherosclerotic lesions.     

Oxidized phospholipids predict the presence and progression of carotid and femoral atherosclerosis and symptomatic cardiovascular disease: five-year prospective results from the Bruneck study.

OBJECTIVES: The purpose of this work was to determine the predictive value of oxidized phospholipids (OxPLs) present on apolipoprotein B-100 particles (apoB) in carotid and femoral atherosclerosis. BACKGROUND: The OxPLs are pro-inflammatory and pro-atherogenic and may be detected using the antibody E06 (OxPL/apoB). METHODS: The Bruneck study is a prospective population-based survey of 40- to 79-year-old men and women initiated in 1990. Plasma levels of OxPL/apoB and lipoprotein (a) [Lp(a)] were measured in 765 of 826 (92.6%) and 671 of 684 (98.1%) subjects alive in 1995 and 2000, respectively, and correlated with ultrasound measures of carotid and femoral atherosclerosis. RESULTS: The distribution of the OxPL/apoB levels was skewed to lower levels and nearly identical to Lp(a) levels. The OxPL/apoB and Lp(a) levels were highly correlated (r = 0.87, p < 0.001), and displayed long-term stability and lacked correlations with most cardiovascular risk factors and lifestyle variables. The number of apolipoprotein (a) kringle IV-2 repeats was inversely related to Lp(a) mass (r = -0.48, p < 0.001) and OxPL/apoB levels (r = -0.46, p < 0.001). In multivariable analysis, OxPL/apoB levels were strongly and significantly associated with the presence, extent, and development (1995 to 2000) of carotid and femoral atherosclerosis and predicted the presence of symptomatic cardiovascular disease. Both OxPL/apoB and Lp(a) levels showed similar associations with atherosclerosis severity and progression, suggesting a common biological influence on atherogenesis. CONCLUSIONS: This study suggests that pro-inflammatory oxidized phospholipids, present primarily on Lp(a), are significant predictors of the presence and extent of carotid and femoral atherosclerosis, development of new lesions, and increased risk of cardiovascular events. The OxPL biomarkers may provide valuable insights into diagnosing and monitoring cardiovascular disease.     

Impaired glucose tolerance, Type II diabetes mellitus and carotid atherosclerosis: prospective results from the Bruneck Study

Abstracts Aims/hypothesis. Cardiovascular disease is a well-known severe complication of impaired glucose tolerance and Type II (non-insulin-dependent) diabetes mellitus. The independent contribution of glucose intolerance to cardiovascular disease and the underlying pathogenic mechanisms are still, however, not clear.?Methods. In this prospective population-based study, 826 subjects aged 40–79 years underwent high resolution duplex ultrasound examinations of carotid arteries and extensive clinical and laboratory screenings for potential vascular risk factors at baseline and 5 years later. The ultrasound protocol involved measurements of maximum axial diameter of atherosclerotic plaques, if any, in common and internal carotid arteries on both sides and enable differentiation of two main stages in carotid artery disease, termed early non-stenotic and advanced stenotic atherosclerosis. Intima-media thickness was assessed at the follow-up examination.?Results. Type II diabetes and, to a lesser extent, impaired glucose tolerance were found to be statistically significant risk predictors of 5-year changes in carotid atherosclerosis. These associations were in part independent of other vascular risk factors typically clustering with glucose intolerance. Both impaired glucose tolerance and Type II diabetes mellitus were not independently related to early non-stenotic atherosclerosis. In contrast, Type II diabetes mellitus was the strongest single risk predictor of advanced stenotic atherosclerosis [odds ratio 5.0 (95 % confidence intervals 2.3–11.1)] and impaired glucose tolerance was of relevance as well [odds ratio 2.8 (1.2–6.4)] (p < 0.001).?Conclusion/interpretation. Impaired glucose tolerance and, to a greater extent, Type II diabetes were strong independent predictors of advanced carotid atherosclerosis in our prospective population-based study. [Diabetologia (2000) 43: 156–164] Received: 29 July 1999 and in revised form: 23 September 1999     

Distinct risk profiles of early and advanced atherosclerosis: prospective results from the Bruneck Study

Most epidemiological surveys on risk factors of atherosclerosis were cross-sectional in design and did not consider the existence of pathologically distinct processes. The Bruneck Study is a prospective survey in the general community (age range, 40 to 79 years). The baseline examination and first reevaluation were performed in the summers of 1990 and 1995 (participation, 92%; follow-up, 96%). Carotid atherosclerosis was monitored with high-resolution duplex ultrasound. Early (incidence and/or extension of nonstenotic lesions) and advanced (incidence and/or progression of stenosis >40%) stages of atherogenesis were differentiated. The risk profile of early atherogenesis consists of traditional risk factors, such as hypertension, hyperlipidemia, and cigarette smoking (pack-years), supplemented by a variety of less well-established risk conditions, including high body iron stores, hypothyroidism, microalbuminuria, and high alcohol consumption. In contrast, the risk profile of advanced atherogenesis includes markers of enhanced prothrombotic capacity, attenuated fibrinolysis, and clinical conditions known to interfere with coagulation: high fibrinogen, low antithrombin, factor V Leiden mutation, lipoprotein(a) >0.32 g/L, high platelet count, cigarette smoking, and diabetes. Hyperlipidemia and hypertension were of only minor relevance. These findings, along with the epidemiological features of advanced atherogenesis and emergence of an elevated fibrin turnover, suggest atherothrombosis to be a key mechanism in the development of advanced stenotic atherosclerosis. Supplementary 6-category logistic regression models illustrate the changing association between major risk predictors and atherosclerosis of increasing severity and substantiate appropriateness of the 40% threshold applied for the definition of advanced stenotic atherosclerosis. Atherosclerosis is a heterogeneous process that subsumes etiologically and epidemiologically distinct disease entities. The multifactorial etiology of atherosclerosis, which goes far beyond the traditional risk factors, has not yet achieved adequate attention in clinical practice and disease prevention.     

颈动脉粥样硬化与冠心病关系的研究

目的研究颈动脉粥样硬化与冠心病的关系。方法对301例冠状动脉造影的患者作双侧颈动脉超声检查，根据冠脉造影结果分为正常组及冠心病组，冠心病组根据冠状动脉病变支数再分为一支病变组，二支病变组，三支病变组3个亚组。测量颈总动脉后壁内中膜厚度(IMT)，斑块厚度，计算斑块积分及粥样斑块发生率。结果(1)冠心病组IMT，斑决积分及斑块发生率明显高于正常对照组(P＜0.01)。(2)随冠脉病变支数增加，斑块积分及IMT增加，亚组比较有显著性差异(P＜0.01)。(3)以IMT＞0.85mm和(或)出现粥样斑块预测冠心病，特异性75.3％，敏感性84.6％，阳性预测率88.4％。结论通过颈动脉超声检查可为冠心痛的诊断提供依据。     

颈动脉粥样硬化与冠心病关系的研究

目的:研究颈动脉粥样硬化与冠心病的关系。方法:对301例冠状动脉造影的患者作双侧颈动脉超声检查,根据冠脉造影结果分为正常组及冠心病组,冠心病组根据冠状动脉病变支数再分为一支病变组,二支病变组,三支病变组3个亚组。测量颈总动脉后壁内中膜厚度(IMT),斑块厚度,计算斑块积分及粥样斑块发生率。结果:(1)冠心病组IMT,斑块积分及斑块发生率明显高于正常对照组(P<0.01)。(2)随冠脉病变支数增加,斑块积分及IMT增加,亚组比较有显著性差异(P<0.01)。(3)以IMT>0.85mm和(或)出现粥样斑块预测冠心病,特异性75.3％,敏感性84.6％,阳性预测率88.4％。结论:通过颈动脉超声检查可为冠心病的诊断提供依据。     

颈动脉粥样硬化与冠心病的相关性研究

目的:探讨颈动脉粥样硬化与冠心病的相关性。方法:对84例拟诊冠心病的患者,行颈动脉超声和冠状动脉造影检查。结果:发现心绞痛组和心肌梗死组的颈动脉粥样硬化(AS)等级积分、Crouse积分和斑块数均明显高于非冠心病组(P<0.01和P<0.001),冠脉单支和多支病变组与非冠心病组的颈动脉粥样硬化指标亦有明显差异(<0.001和P<0.0001);冠脉造影积分和冠脉病变支数与颈动脉粥样硬化的等级积分、Crouse积分和斑块数均呈显著的正相关。颈动脉超声的敏感性为86.4％,特异性为64.0％,总的诊断符合率为79.8％。结论:测定颈动脉粥样硬化斑块的超声病理分型对冠心病的预测具有临床意义。     

High plasma levels of alpha- and beta-carotene are associated with a lower risk of atherosclerosis: results from the Bruneck study

BACKGROUND AND PURPOSE: A large number of studies have contributed to the hypothesis that carotenoids, vitamins A and E are protective against atherosclerosis by acting as antioxidants. The aim of this study was to assess the relationship between plasma levels of carotenoids (alpha- and beta- carotene, lutein, lycopene, zeaxanthin, beta-cryptoxanthin), vitamins A and E, and atherosclerosis in the carotid and femoral arteries. METHODS: This prospective and cross sectional study involved a randomly selected population sample of 392 men and women aged 45-65 years. Carotid and femoral artery atherosclerosis was assessed by high-resolution duplex ultrasound. RESULTS: alpha- and beta- carotene plasma levels were inversely associated with the prevalence of atherosclerosis in the carotid and femoral arteries (P=0.004) and with the 5-year incidence of atherosclerotic lesions in the carotid arteries (P=0.04). These findings were obtained after adjustment for other cardiovascular risk factors (sex, age, LDL (low density lipoproteins), ferritin, systolic blood pressure, smoking, categories of alcohol consumption, social status, C-reactive protein). Atherosclerosis risk gradually decreased with increasing plasma alpha- and beta-carotene concentrations (P=0.004). No associations were found between vitamin A and E plasma levels and atherosclerosis. CONCLUSIONS: This study provides further epidemiological evidence of a protective role of high alpha- and beta- carotene in early atherogenesis.     

应用彩色多普勒超声检测缺血性脑血管病与颈动脉粥样硬化的关系

目的探讨缺血性脑血管病与颈动脉粥样硬化病变之间的关系。方法对130例缺血性脑血管病患者进行颈动脉彩色多普勒超声检查，130例患者中56例短暂性脑缺血发作（TIA），74例脑梗死；42例非缺血件脑血管病患者为对照组。检测颈动脉内膜增厚及斑块形成等血管异常发牛率、斑块类型及斑块的分布情况。结果TIA组患者颈动脉内膜-中层厚度（IMT）增厚及颈动脉硬化斑块等异常检出率为73．2％（41／56），脑梗死组异常率为87．8％（65／74），对照组受检者异常率为28．6％（12／42），TIA组及脑梗死组与对照组比较差异有显著意义（P〈0．01）。脑梗死组患者脂质性斑块及混合性斑块的发生率高于TIA组。颈动脉硬化斑块最常见部位为颈总动脉分又处，其次为颈内动脉近段。左右侧差异无显著意义。结论颈动脉硬化与缺血性脑血管病有密切相关性，颈动脉超声有助于预测缺血性脑血管病的发病危险。     

No association between dehydroepiandrosterone sulfate and development of atherosclerosis in a prospective population study (Bruneck Study)

Antiatherogenic properties of dehydroepiandrosterone (DHEA) have been postulated for >40 years. Large-scale epidemiological studies on this important issue, however, are still sparse, and those available have yielded contradictory results. The Bruneck Study involved a large random sample of men and women aged 40 to 79 years that were enrolled in 1990 and reevaluated 5 years later. Baseline DHEA sulfate (DHEAS) levels were measured in 867 subjects after an overnight fast. Development and progression of carotid atherosclerosis was monitored by high-resolution duplex ultrasound. DHEAS levels declined with advancing age (29% and 44% per decade in men and women) and showed a complex sex-specific association with various vascular risk attributes and factors conferring protection against atherosclerosis. Age- and sex-adjusted DHEAS baseline levels did not differ between subjects with or without incident/progressive atherosclerosis (geometric mean 1161 versus 1253 microg/L). After adjustment for vascular risk factors and potential confounders, the odds ratio of incident/progressive atherosclerosis comparing a 50% increase in DHEAS levels was 0.99 (95% CI 0.89 to 1.11). Lack of an association between DHEAS and atherogenesis was confirmed in sex-specific and a variety of supplementary analyses. Statistical power would be high enough to detect differences in DHEAS between outcome categories as low as 15% (alpha=0.05). This prospective community-based study does not support a role for endogenous DHEA(S) in the development of human atherosclerosis.     

心血管疾病危险人群中微量白蛋白尿与颈动脉粥样硬化及外周动脉疾病的关系

目的评价存在心血管疾病危险因素但无明确心脑血管疾病的患者中,微量白蛋白尿(MA)与颈动脉粥样硬化(AS)及外周动脉疾病(PAD)的关系。方法采用横断面研究,277例住院有心血管疾病危险因素但无明确心脑血管疾病的患者,根据其尿白蛋白/肌酐(UACR)水平分为两组:微量白蛋白尿组(MA组,男:17 mg/g≤UACR≤250 mg/g;女:25 mg/g≤UACR≤355 mg/g)及不伴微量白蛋白尿组(NMA组,男:00.05)。结论心血管疾病高危患者中,伴MA者颈总动脉AS和PAD的危险性均增加,MA与颈总动脉AS的关系较与PAD的关系更加明显。     

脑梗死患者颈动脉病变与眼底动脉硬化的相关性分析

目的探讨脑梗死患者颈动脉病变与眼底动脉硬化的相关性。方法选择脑梗死患者177例,分别进行头颅CT或MRI、颈动脉超声和眼底照相检查,评价颈动脉内膜中层厚度、颈动脉狭窄及眼底动脉硬化分级。结果177例患者中,颈动脉无病变10例(5.6%),颈总动脉内膜中层厚度增厚22例(12.4%),任意颈动脉斑块形成121例(68.4%),颈动脉狭窄24例(13.6%)。正常35例(19.8%),眼底动脉硬化改变142例(80.2%),其中Ⅰ级69例(39.0%),Ⅱ级31例(17.5%),Ⅲ级42例(23.7%)。眼底动脉硬化与颈动脉内膜中层厚度、颈动脉狭窄相关(P<0.05),但眼底动脉硬化各单项指标与颈动脉内膜中层厚度和颈动脉是否狭窄无相关性(P>0.05)。结论眼底动脉硬化与颈动脉病变存在一致性,眼底照相可作为辅助方法帮助评价全身血管情况,协助颈动脉疾病的诊断。     

颈、股动脉粥样硬化超声标识与冠心病的关系研究

目的:利用高频超声研究颈、股动脉粥样硬化超声标识与冠状动脉粥样硬化的关系。方法:对91例冠状动脉造影受检者术前行双侧颈、股动脉超声检查,测定血管后壁内膜中层厚度(IMT)和斑块厚度,记录斑块数目,半定量估计斑块的严重程度。根据冠状动脉造影结果分为正常组和冠心病组。冠心病组分别按血管狭窄≥50%所累及主要病变血管支数分:单支病变、双支病变、3支病变,其中左主干累及定为双支病变。结果:随着冠状动脉病变程度的增加,颈、股动脉IMT值均增加,冠心病组与正常组比较差异有统计学意义(P<0.05);颈、股动脉斑块分级与冠状动脉病变血管支数分级间显著相关(P<0.05);股动脉斑块对冠心病预测的准确度(69.23%)高于颈动脉斑块(56.04%)。结论:颈、股动脉粥样硬化超声标识似用以预测冠心病的严重程度。     

Self-reported snoring and incident cardiovascular disease events: results from the Jackson Heart Study

Sleep and Breathing - Evidence suggests that snoring is associated with increased risk for cardiovascular disease (CVD) events such as myocardial infarction and stroke. Limited data exists...