Endothelial microparticles correlate with endothelial dysfunction in obese women

CONTEXT: Cell-derived microparticles are supposed to be involved in atherogenesis. OBJECTIVE: This study aimed to evaluate circulating microparticles in obese women and their relation with anthropometric measures and endothelial dysfunction. DESIGN, SETTING, AND PARTICIPANTS: Forty-one obese [body mass index (BMI) > 30 kg/m(2)] women and 40 normal weight (BMI < 25 kg/m(2)) age-matched women were studied. Flow cytometry was used to assess microparticles by quantification of circulating endothelial microparticles (EMP, CD31+/CD42b-) and platelet microparticles (PMP, CD31+/CD42b+) in peripheral blood; endothelium-dependent flow-mediated vasodilation (FMD) was evaluated in the right brachial artery after reactive hyperemia. RESULTS: Compared with lean women, obese women presented significantly higher numbers of EMP and PMP, and reduced FMD. BMI did not correlate with either EMP (r = 0.02, P = 0.9) or PMP (r = -0.07, P = 0.645), whereas waist-to-hip ratio (WHR) showed significant correlation with both microparticles (r = 0.699, P < 0.001; r = 0.373, P = 0.016, respectively). Both EMP and PMP counts positively correlated with impairment of FMD in obese women. Multivariate analysis correcting for age, anthropometric indices, lipid parameters, and PMP identified EMP as the only independent predictor for impaired endothelial-dependent vasodilation (P = 0.003). CONCLUSIONS: EMP are elevated in obese women and independently involved in the pathogenesis of endothelial dysfunction. WHR is the anthropometric measure more closely related to EMP and endothelial dysfunction.     

High levels of circulating endothelial microparticles in patients with acute coronary syndromes

Background

Endothelial injury plays a critical role in coronary artery disease (CAD), but the assessment of this injury has been problematical. Recently, it has been shown in vitro that endothelial cells (ECs) release endothelial microparticles (EMPs) on activation or apoptosis and that an assay of EMPs can provide useful information on EC status in patients with thrombotic disorders. This study is aimed at assessing possible correlations between EMPs, which are markers of endothelial injury, and clinical subgroups of patients with CAD.

Methods

A prospective, case-controlled study was conducted on 84 patients with CAD and 42 control subjects to investigate EMP profiles. Included were 64 patients with acute coronary syndromes ([ACS], 38 with myocardial infarction [MI] and 26 with unstable angina [UA]) and 20 patients with stable angina (SA). EMPs in platelet-poor plasma were measured flow cytometrically with combinations of fluorescent antibodies (anti-CD31, -51, -42), allowing distinction of EMPs from platelet microparticles (PMPs). Clinical subgroups of patients were correlated with EMP and PMP levels in blood.

Results

Two species of EMPs (CD31+ and CD51+) were evaluated. Both were significantly higher in patients with CAD than in control subjects. CD31+ EMP was higher in ACS than SA. Among patients with first MI, CD31+ EMP was higher in patients with MI than in patients with UA and was significantly higher than in patients with recurring MI. CD51+ EMP did not discriminate ACS from SA. A simultaneous assay of PMP showed correlation between EMPs and PMPs. However, PMPs did not discriminate patients with SA from control subjects.

Conclusions

EMP assay appears promising for assessing EC injury in CAD.     

Percutaneous coronary intervention therapy improved prognosis of high-risk patients with acute coronary syndromes

Objective In this study, we evaluated the effects of pereutaneous coronary intervention (PCI) therapy on prognosis of high-risk patients with acute coronary syndromes(ACS). Methods From September, 2001 to July, 2002 we continuously observed 110 eases of ACS patients, including 70 cases of acute myocardial infarction (AMI)and 40 cases of anstable angin apeetoris(UAP).     

Endothelial dysfunction as a predictor of acute coronary syndromes

Endothelial dysfunction is a key early event in atherogenesis and is integral in the onset of acute coronary syndromes. Disruption of the normal endothelial functions leads to loss of vasomotor control, reduced production of nitric oxide, formation of a procoagulant surface, and promotion of inflammation. These events may lead to destabilization of atherosclerotic plaques and the onset of acute coronary syndromes. There are several direct and indirect ways of assessing endothelial dysfunction in vivo. Several of these measures of endothelial dysfunction have been shown to correlate with increased risk of adverse cardiovascular outcomes.     

内皮微粒与冠心病

完整的单层内皮细胞屏障在维持血管的正常结构、功能及抗粥样硬化中起着关键作用。内皮细胞通过释放抗凝、抗炎物质及扩张血管等作用起到抗动脉粥样硬化作用。当内皮细胞激活、损伤和（或）凋亡时,向细胞外释放内皮微粒（EMP）。EMP可以促进血栓形成和炎症反应,影响血管内皮功能,并且在动脉粥样硬化、冠心病、冠心病危险因素（如高血压、吸烟、代谢综合征和糖尿病）等状态下,其体内水平明显升高。     

Emerging importance of HDL cholesterol in developing high-risk coronary plaques in acute coronary syndromes

Cardiovascular disease is the principal cause of death in industrialized countries. Hyperlipidemia, with high low-density lipoprotein cholesterol and triglycerides, and low high-density lipoprotein cholesterol levels (<40 mg/dL in men and <45 mg/dL in women), is a known major cardiovascular risk factor. Statins are considered the most potent and effective agents to reduce low-density lipoprotein cholesterol, but they have a variable effect on high-density lipoprotein cholesterol and triglycerides. Different clinical trials with statins have shown a decrease in low-density lipoprotein cholesterol by 35% and a reduction of the incidence of coronary events by as much as 30%. However, 60 to 70% of events still occur, despite remarkable reduction of low-density lipoprotein cholesterol concentration. Recent National Cholesterol Education Program guidelines highlighted the importance of high-density lipoprotein cholesterol concentration in the prevention and treatment of cardiovascular disease. High-density lipoprotein cholesterol is considered an independent risk factor and has an inverse relation with coronary events. The association of low levels of high-density lipoprotein cholesterol with an increased incidence of cardiovascular events implies a critical role of high-density lipoprotein in the protection against atherosclerotic disease and in the progression of coronary atherosclerotic disease. High-density lipoprotein cholesterol appears to exert this protective effect through multiple mechanisms. High-density lipoprotein is not only involved in reverse cholesterol transport, but also prevents endothelial dysfunction; inhibits the homing of monocytes, apoptosis, platelet activation, and factor X activation; and has antioxidant properties. In this article the authors review the available experimental and clinical evidence supporting the importance of high-density lipoprotein cholesterol as a protective factor in coronary artery disease, and the strategies developed to increase high-density lipoprotein cholesterol.     

Multislice computed tomographic characteristics of coronary lesions in acute coronary syndromes.

OBJECTIVES: To evaluate the feasibility of noninvasive assessment of the characteristics of disrupted atherosclerotic plaques, the authors interrogated the culprit lesions in acute coronary syndromes (ACS) by multislice computed tomography (CT). BACKGROUND: Disrupted atherosclerotic plaques responsible for ACS histopathologically demonstrate large lipid cores and positive vascular remodeling. It is expected that plaques vulnerable to rupture should bear similar imaging signatures by CT. METHODS: Either 0.5-mm x 16-slice or 64-slice CT was performed in 38 patients with ACS and compared with 33 patients with stable angina pectoris (SAP) before percutaneous coronary intervention. The coronary plaques in ACS and SAP were evaluated for the CT plaque characteristics, including vessel remodeling, consistency of noncalcified plaque (NCP <30 HU or 30 HU 相似文献   

High yellow color intensity by angioscopy with quantitative colorimetry to identify high-risk features in culprit lesions of patients with acute coronary syndromes

High yellow color intensity (HYCI) regions of atherosclerotic plaque, determined by angioscopy with quantitative colorimetry, are associated with lipid cores underneath thin fibrous caps in ex vivo tissue samples. To determine whether HYCI regions of coronary plaque are associated with disruption or thrombus in living patients, quantitative colorimetry was applied to angioscopy, and the color of culprit lesions was measured in patients with acute coronary syndromes. In 46 patients with acute coronary syndromes (acute myocardial infarction, n = 14; unstable angina pectoris [UAP] with culprit thrombus, n = 16; and UAP without culprit thrombus, n = 16), the recorded angioscopic images of culprit lesions were analyzed using a quantitative colorimetric method based on the L*a*b* color space applied to angioscopy (positive b* = yellow color intensity). HYCI was defined as b* value >23. Plaque disruption was significantly more prevalent in 19 of 24 HYCI regions (79%) than in 9 of 22 non-HYCI regions (41%) (p = 0.007). Culprit HYCI regions were prevalent in patients with myocardial infarction (11 of 14 [79%]), followed by those with UAP with thrombus (9 of 16 [56%]) and UAP without thrombus (4 of 16 [25%]) (p = 0.01 for trend), and were significantly more prevalent in 66% of patients with myocardial infarction and UAP with thrombus compared with 25% of those with UAP without thrombus (p = 0.007). In conclusion, HYCI regions of coronary plaque may be indicative of high-risk lesions vulnerable to thrombosis. Coronary angioscopy with quantitative colorimetry could be used to study the association between high-risk coronary lesions and future cardiovascular events.     

急性冠脉综合征患者并发焦虑障碍与冠状动脉狭窄严重程度的相关性

目的:探讨急性冠脉综合征(ACS)患者并发焦虑障碍患者焦虑评分与冠状动脉狭窄严重程度的关系。方法:180例ACS患者采用Zung焦虑自评量表(SAS)测试评分,分为焦虑组和非焦虑组,并行冠状动脉造影检查及心脏彩超检查测左室射血分数(LVEF),对冠状动脉病变狭窄程度进行Gensini评分,分析SAS评分与ACS患者冠状动脉病变评分(Gensini评分)的关系。结果:根据SAS评分将ACS患者分为无焦虑组82例,焦虑组98例(轻度焦虑54例,中度30例,重度14例)。焦虑组冠状动脉病变评分(Gensini评分)为(36±22)分,显著高于无焦虑组Gensini评分(25±13)分(P<0.01)。SAS评分与冠状动脉病变Gensini积分呈正相关(r=0.36,P<0.01)。结论:ACS患者焦虑障碍程度与冠脉病变狭窄程度相关。     

Intravascular evaluation of coronary atherosclerotic lesions among Egyptian diabetic patients with acute coronary syndromes

Background

Coronary artery disease is one of the main causes of death in diabetes mellitus (DM). Egypt was listed among the world top 10 countries regarding the number of diabetic patients by the International Diabetes Federation (IDF).

Regional outcomes after admission for high-risk non-ST-segment elevation acute coronary syndromes

Purpose

An analysis of reginal variation across the United States in the treatment and outcomes of patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) has not been previously performed.

Subjects and Methods

We assessed contemporary practice and outcomes in 56,466 high-risk patients with NSTE ACS (positive cardiac markers and/or ischemic ST-segment changes) admitted to 310 hospitals across four defined regions in the United States from January 1, 2001, to September 30, 2003. Patient clinical characteristics, acute (<24 hours) and discharge medications, in-hospital procedures, and in-hospital case-fatality rates were evaluated.

Results

Statistically significant but clinically small differences in baseline characteristics including age, gender, rates of diabetes, hypertension, and smoking, as well as medical treatment, including a greater than 5% variation in acute use of beta-blockers, clopidogrel, and statins use, were noted across regions. Adjusted rates of revascularization were similar across regions. Overall in-hospital case-fatality rate was 4.1%, with the highest rates in the Midwest (4.6%) and the lowest in the Northeast (3.5%). Adjusted odds ratios (OR) (95% confidence interval [CI] for death were significantly higher in the Midwest (OR 1.42, CI 1.19-1.70), West (OR 1.40 CI 1.05-1.87), and South (OR 1.33, CI 1.08-1.62), compared with the Northeast.

Conclusions

Management of high-risk patients with NSTE ACS is relatively uniform across the United States. However, in-hospital case-fatality rates vary significantly by region, and the differences are not explained by adjustment for standard clinical variables.     

Alterations in serum neopterin correlate with thrombolysis in myocardial infarction risk scores in acute coronary syndromes

OBJECTIVES: Using serum neopterin as a marker of macrophage activation, we sought to examine the relationship between serum neopterin levels, thrombolysis in myocardial infarction (TIMI) risk scores, and how different treatments of acute coronary syndromes affect change in neopterin. METHODS: We examined serum neopterin concentrations at presentation and 72 h after treatment in 70 patients with acute coronary syndromes (35 with medical therapy, 25 with uncoated coronary stents, and 10 received rapamycin-eluting stents) using a commercially available immunoassay. Serum neopterin levels were determined for 36 patients with stable coronary artery disease. TIMI risk scores were calculated when appropriate (n=58). RESULTS: Serum neopterin had a strong correlation with the TIMI risk score on admission (P<0.0001). The mean baseline neopterin levels in patients with acute coronary syndromes stratified with TIMI scores between 1 and 7 were the following: patients with TIMI 1 scores had a level of 3.3+/-0.4 nmol/l, TIMI 2 patients 4.6+/-0.6 nmol/l, TIMI 3 patients 5.5+/-1.4 nmol/l, TIMI 4 patients 7.5+/-2.4 nmol/l, TIMI 5 patients 10.8+/-3.3 nmol/l, TIMI 6 patients 17.5+/-4.0 nmol/l, and TIMI 7 patients 23.0+/-7.1 nmol/l. Mean changes in serum neopterin were significantly higher for the uncoated stent group than for each of the other three groups (P<0.05). CONCLUSIONS: Serum neopterin concentrations have a high correlation with TIMI risk scores and may represent a marker useful in stratifying patients with acute coronary syndromes. Our results also suggest that the use of uncoated coronary stents results in macrophage activation not found with other treatment modalities.     

Endothelial microparticles exert differential effects on functions of Th1 in patients with acute coronary syndrome

Background

Endothelial microparticles (EMPs) can be involved in inflammatory process, blood coagulation, and regulation of vascular function. However, it remains unclear whether EMPs participate in the pathogenesis of ACS. The purpose of this study is to investigate the impact of EMPs on Th1/Th2 development and functions in vitro.

Methods

Eight-five patients were allocated into SAP group (n = 27), UAP group (n = 28), and AMI group (n = 30). Twenty hospitalized patients with normal coronary angiography were recruited as controls. The frequency of EMPs, IFN-γ, and IL-4 levels were measured, and the correlation between EMPs and Th1/Th2 cytokine was analyzed. PBMCs isolated from patients with ACS were treated in vitro with EMPs. This was followed by flow cytometry for Th1/Th2 counts, real-time PCR and western blotting for T-bet and GATA mRNA and protein expression, and ELISA for IFN-γ, TNF-α, IL-4, and IL-10.

Results

This study proved that the frequency of EMPs was significantly increased in ACS patients. There was a significant positive correlation between EMPs and IFN-γ. EMPs could significantly upregulate the differentiation and function of Th1 through increasing the expression of T-bet mRNA and protein. Furthermore, this study also indicated that EMP treatment in vitro could promote the expression of TNF-α, which exerts adverse effects on the pathogenesis and progression of atherosclerosis.

Conclusions

EMPs may be involved in the immune and inflammatory processes that take part in artery atherosclerosis and that they do so by regulating Th1/Th2 differentiation and function. They may play an important role in the pathogenesis of coronary atherosclerosis and plaque instability.     

Effect of abciximab on clinical and angiographic restenosis in patients with non-ST-segment elevation acute coronary syndromes

The ISAR-REACT 2 trial was designed to assess the effect of abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after a 600-mg loading dose of clopidogrel. The aim of the present study was to investigate the impact of abciximab on clinical and angiographic restenosis after coronary stenting in patients with acute coronary syndromes. The angiographic substudy included 1,544 patients from the ISAR-REACT 2 trial randomly assigned to abciximab (771 patients) or placebo (773 patients). All patients were scheduled for routine angiographic follow-up at 6 to 8 months after intervention. The primary end point was incidence of angiographic in-segment binary restenosis. The secondary end point was 1-year incidence of target-lesion revascularization. Binary restenosis was observed in 21.9% of patients in the abciximab group and 24.5% of patients in the placebo group (p=0.29). Percentages of in-stent (29+/-22% vs 33+/-24%; p=0.02) and in-segment (35+/-20% vs 38+/-21%; p=0.04) diameter stenoses were significantly lower in the abciximab group than the placebo group. There was a strong trend toward lower 1-year incidence of target-lesion revascularization in patients treated with abciximab than in patients treated with placebo (13.6% vs 16.8%; p=0.08). In conclusion, in patients with non-ST-segment elevation acute coronary syndromes undergoing early percutaneous coronary intervention with stenting after a 600-mg loading dose of clopidogrel, abciximab therapy may have a slight positive impact on the prevention of restenosis.     

Correlation of TIMI risk score with angiographic extent and severity of coronary artery disease in non-ST-elevation acute coronary syndromes

Aim of study

To determine whether the TIMI risk score correlates with the angiographic extent and severity of coronary artery disease in patients with non-ST-elevation acute coronary syndrome undergoing cardiac catheterization.

Patients and method

We conducted a retrospective review of 239 medical records of patients who underwent coronary angiography secondary to non-ST-elevation acute coronary syndrome between 2002 and 2006. Patients were classified into three groups according to TIMI risk score: TIMI scores 0 to 2 (group 1: n = 121), 3 to 4 (group 2: n = 100), and 5 to 7 (group 3: n = 18). We compared the coronary angiography findings of the three groups.

Results

Patients of group 1 had a greater likelihood of normal or non significant CAD than patients of group 2 (36.3 % vs 13 %, P < 0.001) and than patients of group 3 (36.3 % vs 0 %, P = 0.002). One-vessel disease was found more often in patients with TIMI score 0 to 2 than in patients with TIMI score 5 to 7 (28.9 % vs 0 %; P = 0.01), and in patients with TIMI score 3 to 4 than in those with score 5 to 7 (35 % vs 0 %, P = 0.006). However, 1-vessel disease was found in patients of group 1 as often as in patients of group 2. The frequency of two-vessel disease was similar whatever the level of TIMI score was low, intermediate or high. Three-vessel or left main disease was more likely found in patients of group 3 than in patients of group 2 (66.7 % vs 26 %; P = 0.01), and than patients of group 1 (66.7 % vs 13.2 %; P < 0.001). Chronic coronary occlusions and coronary calcifications were also more likely found in patients with TIMI score 5 to 7.

Conclusion

In patients with non-ST-elevation acute coronary syndrome undergoing cardiac catheterization, the TIMI risk score correlated with the extent and severity of coronary artery disease.     

替罗非班对高危非ST段抬高型急性冠脉综合征的疗效评价

目的 通过与常规治疗方案对比来评估替罗非班对高危非ST段抬高型急性冠状动脉（冠脉）综合征的疗效.方法 将自2012年2月至2013年10月在北京市大兴区人民医院就诊并诊断为高危非ST段抬高型急性冠脉综合征并符合纳入标准的患者226例随机分为替罗非班治疗的试验组和安慰剂治疗的对照组,其中试验组114例,对照组112例.分别在治疗后的第7、第14、第30和第90天（T1、T2、T3和T4）对观察指标进行测量并记录.研究的主要终点指标包括致命和非致命的心肌梗死,次要终点指标包括心脏原因以外的死亡和药物治疗无效的难治性心肌缺血.结果 与对照组相比,试验组主要终点事件的发生显著减少.试验组和对照组第7天时发生的主要终点事件分别是9和21例（P=0.039）;第14天分别是10和26例（P=0.021）;第30天分别是10和29例（P=0.019）;第90天分别是13和34例（P=0.012）.结论 研究结果证实替罗非班可以改善高危非ST段抬高型急性冠脉综合征患者的预后,疗效确切.