Endothelial dysfunction occurs in peripheral circulation patients with acute and stable coronary artery disease

Atherosclerosis is a diffuse, systemic process. In addition, acute coronary syndromes (ACS) are associated with inflammatory marker elevations that are hypothesized to affect the function of nonculprit coronary as well as peripheral vessels. We investigated whether femoral vascular reactivity and/or fibrinolytic capacity are impaired in ACS patients over and above any dysfunction associated with stable coronary artery disease. Patients undergoing diagnostic coronary angiography (n = 42 total, 14 patients/group) were recruited into three groups as follows: 1) stable coronary syndromes (SAP group), 2) ACS as defined by rest angina with ECG changes and troponin rise (ACS group), and 3) angiographically normal coronary arteries (control group). After diagnostic coronary angiography, femoral artery endothelial and smooth muscle function were assessed by infusing acetylcholine (ACh) and nitroglycerin (GTN), and tissue-type plasminogen activator (t-PA) release across the femoral circulation was measured as the difference between arterial and venous concentrations before and after ACh and GTN stimulation. There were no significant differences between groups in relevant baseline characteristics apart from significantly higher C-reactive protein levels and reduced net t-PA release in the ACS group at baseline (P < 0.05). The ACS and SAP groups had equivalent angiographic severity of coronary artery disease. Endothelium-dependent dilatation was significantly higher in control individuals (14.9 +/- 9.1%; P < 0.001) compared with either stable patients (2.3 +/- 8.1%) or those with unstable syndromes (2.6 +/- 8.9%, who were similar to each other; P = not significant). Although baseline t-PA release was impaired in the ACS patients (0.09 +/- 0.06 compared with 0.39 +/- 0.33 and 0.49 +/- 0.56 ng/ml; P = 0.03), stimulation of t-PA release by ACh and GTN occurred only in the control subjects and not in the ACS or SAP patients. Coronary artery disease is associated with impaired endothelium-dependent dilatation and impaired stimulation of t-PA release in the systemic circulation. These aspects of endothelial dysfunction, however, were equally severe in acute and chronic coronary syndrome patients.     

Mild inflammatory activation of mammary arteries in patients with acute coronary syndromes

Acute coronary syndromes (ACS) are characterized by multiple unstable coronary plaques and elevated circulating levels of inflammatory biomarkers. The endothelium of internal mammary arteries (IMA), which are atherosclerosis resistant, is exposed to proinflammatory stimuli as vessels that develop atherosclerosis. Our study investigated the IMA endothelial expression of inflammatory molecules in patients with ACS or chronic stable angina (CSA). IMA demonstrated normal morphology, intact endothelial lining, and strong immunoreactivity for glucose transporter 1. E-selectin expression was observed more frequently in IMA of ACS patiention than CSA patients (ACS 61% vs. CSA 14%, P = 0.01). High fluorescence for major histocompatibility complex (MHC) was significantly more frequent on the luminal endothelium (ACS 66.7% vs. CSA 17.6%, P = 0.001 for class I; and ACS 66.7% vs. CSA 6.2%, P = 0.0003 for class II-DR) and on the vasa vasorum (ACS 92.9% vs. CSA 33.3% and 7.7%, P = 0.0007 and P < 0.0001 for class I and class II-DR, respectively) of ACS patients than CSA patients. ICAM-1, VCAM-1, Toll-like receptor 4, tissue factor, IL-6, inducible nitric oxide synthase, and TNF-alpha expression were not significantly different in ACS and CSA. Circulating C-reactive protein [ACS 4.8 (2.6-7.3) mg/l vs. CSA 1.8 (0.6-3.5) mg/l, P = 0.01] and IL-6 [ACS 4.0 (2.6-5.5) pg/ml vs. CSA 1.7 (1.4-4.0) pg/ml, P = 0.02] were higher in ACS than CSA, without a correlation with IMA inflammation. The higher E-selectin, MHC class I and MHC class II-DR on the endothelium and vasa vasorum of IMA from ACS patients suggests a mild, endothelial inflammatory activation in ACS, which can be unrelated to the presence of atherosclerotic coronary lesions. These findings indicated IMA as active vessels in coronary syndromes.     

Troponin elevation in patients with various tachycardias and normal epicardial coronaries

Troponin elevation is usually synonymous with acute coronary syndrome (ACS). Although sensitive for ACS, the elevation of serum troponin, in the absence of clinical evidence of ischemia, should prompt a search for other etiologies of myocardial necrosis. In fact, elevated values of troponin are correlated with myocardial necrosis even though it does not discriminate the mechanism involved. We report a series of seven patients (age range 18-67 years), who presented with complaints of chest discomfort and were found to have regular supraventricular tachycardia (5 patients) and one patient each with atrial fibrillation and ventricular tachycardia. All these patients had elevated troponin I and underwent coronary angiography that revealed normal epicardial coronary arteries. This is first case series in which all patients underwent coronary angiography and none of the patients was hemodynamically unstable at the time of presentation. Patients with elevated troponin due to conditions other than ACS can receive inappropriate and delayed definitive diagnosis and treatment.     

Serum biomarker discovery related to pathogenesis in acute coronary syndrome by proteomic approach

Acute coronary syndrome (ACS) results from inadequate supply of blood flow from the coronary arteries to the heart or ischemia. ACS has an extremely high morbidity and mortality. The levels of biomarkers currently used for detection of ACS also increase in response to myocardial necrosis and other diseases and are not elevated immediately after symptoms appear, thus limiting their diagnostic capacity. Therefore, we aimed to discover new ACS diagnostic biomarkers with high sensitivity and specificity that are specifically related to ACS pathogenesis. Sera from 50 patients with ACS and healthy controls (discovery cohort) each were analyzed using mass spectrometry (MS) to identify differentially expressed proteins, and protein candidates were evaluated as ACS biomarkers in 120 people in each group (validation cohort). α-1-acid glycoprotein 1 (AGP1), complement C5 (C5), leucine-rich α-2-glycoprotein (LRG), and vitronectin (VN) were identified as biomarkers whose levels increase and gelsolin (GSN) as a biomarker whose levels decrease in patients with ACS. We concluded that these biomarkers are associated with the pathogenesis of ACS and can predict the onset of ACS prior to the appearance of necrotic biomarkers.     

急性冠脉综合征患者CD4~+T淋巴细胞亚群的变化及临床意义

目的:研究急性冠脉综合征(ACS)患者CD4+T淋巴细胞亚群的变化及临床意义。方法:收集2013年3月-2014年3月入住我院首次行冠脉成形术(PCI)治疗的ACS患者88例以及造影结果正常患者28例。分别于冠脉造影时取冠脉血流式细胞技术检测CD4+T细胞亚群Th1/Th2、Th17/Treg比例表达变化。结果:与对照组相比,ACS组患者冠脉血中Th1、Th17细胞占CD4+T淋巴细胞的百分比显著升高,而Th1、Treg细胞占CD4+T淋巴细胞的百分比显著降低,差异具有统计学意义(P0.05)。结论:ACS患者体内免疫反应增强,CD4+T淋巴细胞不同功能亚群均参与了动脉粥样硬化(AS)的发生发展,Th1、Th17可促进AS的进展和不稳定性,而Th1、Treg作用相反。     

Proteomic changes related to "bewildered" circulating platelets in the acute coronary syndrome

Acute coronary syndromes (ACS) are associated with platelet activation. The aim of the present study was to study the protein expression level associated with glycolysis, oxidative stress, cytoskeleton and cell survival in platelets obtained during an ACS. Platelets from 42 coronary ischemic patients, divided into patients admitted within 24 h after the onset of chest pain (ACS group; n=16) and patients with stable coronary ischemic disease (CAD, n=26), were analyzed using proteomics. The expression levels of proteins involved in cellular cytoskeleton (F‐actin capping, β‐tubulin, α‐tubulin isotypes 1 and 2, vinculin, vimentin and two Ras‐related protein Rab‐7b isotypes), glycolysis pathway (glyceraldehyde‐3‐phosphate dehydrogenase, lactate dehydrogenase and two pyruvate kinase isotypes) and cellular‐related antioxidant system (manganese superoxide dismutase) and even the expression and activity of glutathione‐S‐transferase were significantly reduced in platelets from ACS patients compared to CAD patients. Moreover, reduction in the expression of proteins associated with cell survival such as proteasome subunit β type 1 was also observed in ACS platelets compared with CAD platelets. Principal component and logistic regression analysis suggested the existence of factors (proteins) expressed in the platelets inversely associated with acute coronary ischemia. In summary, these results suggest the existence of circulating antioxidant, cytoskeleton and glycolytic‐“bewildered” platelets during the acute phase of a coronary event.     

Increased plasma levels of intermedin and brain natriuretic peptide associated with severity of coronary stenosis in acute coronary syndrome

Intermedin (IMD) is a newly discovered peptide with increased levels in plasma and cardiac tissue in mice with ischemia/reperfusion. Continuous administration of low dose IMD markedly elevated the mRNA abundance of myocardial BNP in rats. Plasma BNP levels may reflect the severity of degree of coronary stenosis in patients with acute coronary syndrome (ACS). However, the role of circulating IMD in coronary heart disease remains unclear. We aimed to examine the plasma content of IMD and brain natriuretic peptide (BNP) and its clinical significance in patients with ACS. We collected plasma samples from 41 patients with ACS and 31 controls and measured IMD and BNP levels by radioimmunoassay. The severity of coronary artery stenosis for patients with ACS was measured by coronary angiography. Plasma IMD and BNP levels were markedly higher in ACS patients than that in controls (P < 0.05). The increased plasma IMD and BNP were positively correlated with degree of coronary stenosis in ACS patients (r = 0.263 and r = 0.238, respectively, both P < 0.05). In addition, plasma levels of IMD were positively correlated with BNP levels.     

Levels of BNP and Stress Blood Glucose in Acute Coronary Syndrome Patients and Their Relationships with the Severity of Coronary Artery Lesion

This study aims to analyze the clinical significance of the measuring B-type natriuretic peptide (BNP) and stress glycemia in patients with acute coronary syndrome (ACS), and to investigate the relationships between the two biomarkers and the severity of coronary artery lesions. One hundred and five consecutive patients with ACS admitted for coronary artery angiography were divided into three clinical subgroups. These patients were then further assigned into either of three subgroups according to their Gensini score. Moreover, a group of patients with stable angina (SA) and those with no history of coronary disease served as controls. The patients’ BNP levels were analyzed on admission and their fasting blood glucose was measured the next morning. BNP and fasting blood glucose concentrations were highly elevated in patients with ACS irrespective of their subgroups compared to SA and control patients. This observation was statistically significant (P < 0.001). Further, the concentrations of BNP and fasting blood glucose between the three ACS subgroups were significantly different (P < 0.001) depending on the severity of the coronary artery disease. There is a positive correlation between levels of BNP and blood glucose concentration and Gensini score in ACS patients (r = 0.782, P < 0.05, r = 0.732, P < 0.05). BNP level and stress glycemia were significantly higher in ACS patients than those in SA and control groups. There is a correlation between BNP level and stress blood glucose concentration and the severity of coronary artery lesions. Combined analysis of BNP and stress blood glucose can be helpful and effective for risk stratification of patients with ACS after admission.     

冠脉PCI治疗后血浆脂蛋白相关磷脂酶A2与基质金属蛋白酶-9水平的变化及临床意义

目的:探讨冠脉经皮冠状动脉介入(PCI)治疗后血浆脂蛋白相关磷脂酶A2(LP-PLA2)与基质金属蛋白酶-9(MMP-9)水平的变化及其临床意义。方法:选择150例急性冠脉综合征(ACS)患者、128例稳定型心绞痛(SAP)患者及100例健康者分为作为ACS组、SAP组及对照组。比较三组入院时血浆MMP-9、LP-PLA2水平及ACS组经PCI治疗前后血浆MMP-9、LP-PLA2水平的变化。结果:与对照组比较,SAP组与ACS组的血浆MMP-9、LP-PLA2水平均明显增高(P0.05);与SAP组比较,ACS组明显增高(P0.05)。与术前比较,ACS组术后血浆MMP-9、LP-PLA2水平明显降低(P0.05)。MMP-9与LP-PLA2在ACS组血浆中呈显著正相关(r=0.617,P0.05),在SAP组与对照组中无相关性(P0.05)。结论:冠脉病变程度越严重,血浆MMP-9和LP-PLA2水平更高;PCI治疗后冠脉斑块趋于稳定,血浆MMP-9和LP-PLA2水平降低,且二者有相关性,提示MMP-9和LP-PLA2参与冠状动脉粥样硬化的发病与发展,且对预测ACS高危人群及评价疗效有一定的临床价值。     

Blood histamine is associated with coronary artery disease,cardiac events and severity of inflammation and atherosclerosis

Background : Mast cells are prevalent in the shoulder of unstable atheromas; cardiac mast cells secrete proteases capable of activating matrix metalloproteinases. Histamine is essential in the inflammatory cascade of the unstable plaque. Ascorbate depletion has been correlated with histaminemia which has been shown to impair endothelial-dependent vasodilation. This study evaluates whether oxidative stress as measured by isoprostanes (PGF_2α) coupled with an inflammatory state characterized by histaminemia predisposes patients to acute coronary syndrome (ACS).
Methods : Whole blood histamine, serum vitamin C, and serum PGF_2α levels were drawn on 50 patients with ACS as determined by standard diagnostic criteria, 50 patients with stable coronary artery disease (SCAD), and 50 age and sex matched normal controls (C).
Results : Data were analyzed by stepwise discriminant and Spearman's rank correlation coefficient. A significant relationship exists between histamine and PGF_2α. As PGF_2α rises above 60 pg/mL, an increase in histamine occurs in both the ACS and SCAD groups. A significant inverse relationship exists between ascorbate and histamine in the ACS versus C groups (P < 0.01) and the SCAD versus C groups (P < 0.01).
Conclusion : Histamine and isoprostane levels increase in SCAD and ACS patients. Mast cell activation and lipid oxidation generated during atherosclerosis manifest this inflammatory response. Accelerated isoprostane formation and depleted ascorbate paired with histaminemia is active in CAD and predispose patients to acute coronary syndrome. Blood histamine alone may be a better risk factor for coronary events, and a better prognostic indicator than CRP even when combined with lipid indexes.     

Phenotype commitment in vascular smooth muscle cells derived from coronary atherosclerotic plaques: differential gene expression of endothelial nitric oxide synthase

Unstable angina and myocardial infarction are the clinical manifestations of the abrupt thrombotic occlusion of an epicardial coronary artery as a result of spontaneous atherosclerotic plaque rupture or fissuring, and the exposure of highly thrombogenic material to blood. It has been demonstrated that the proliferation of vascular smooth muscle cells (VSMCs) and impaired bioavailabilty of nitric oxide (NO) are among the most important mechanisms involved in the progression of atherosclerosis. It has also been suggested that a NO imbalance in coronary arteries may be involved in myocardial ischemia as a result of vasomotor dysfunction triggering plaque rupture and the thrombotic response. We used 5' nuclease assays (TaqMan PCRs) to study gene expression in coronary plaques collected by means of therapeutic directional coronary atherectomy from 15 patients with stable angina (SA) and 15 with acute coronary syndromes (ACS) without ST elevation. Total RNA was extracted from the 30 plaques and the cDNA was amplified in order to determine endothelial nitric oxide synthase (eNOS) gene expression. Analysis of the results showed that the expression of eNOS was significantly higher (p<0.001) in the plaques from the ACS patients. Furthermore, isolated VSMCs from ACS and SA plaques confirmed the above pattern even after 25 plating passages. In situ RT-PCR was also carried out to co-localize the eNOS messengers and the VSMC phenotype. The eNOS gene was more expressed in ACS plaques and VSMCs cultured from them, thus indicating that: a) the expression of the most important differentiation markers is retained under in vitro conditions; and b) NO may play a pivotal role in coronary artery disease. Our findings suggest a new cell system model for studying the pathophysiology of unstable angina and myocardial infarction.     

血清MCP-1、RANTES及CysC联合检测对急性冠状动脉综合征的诊断价值

目的:探讨联合检测血清单核细胞趋化蛋白-1(MCP-1)、活化T细胞趋化因子(RANTES)及半胱氨酸蛋白酶抑制剂C(Cys C)对急性冠状动脉综合征(ACS)患者的早期诊断和预后评估价值。方法:选择200例于2012年10月到2013年10月在本院就诊的冠心病患者200例,其中ACS患者120例(为ACS组),另稳定型心绞痛(SAP)患者80例(SAP组),另选择同期40例健康人为对照组。115例患者有冠状动脉粥样硬化,其中40例钙化斑块组、42例纤维斑块组及33例软斑块组,进行CT检查;用双抗体夹心酶联免疫(ELISA)法检测患者血清MCP-1、RANTES、Cys C及高敏C反应蛋白(Hs-CRP)水平,并用logistic回归方程评价联合检测MCP-1、RANTES及Cys C预测ACS的效果。结果:与SAP组、对照组相比,ACS组患者MCP-1、RANTES、Cys-C、Hs-CRP、LDL-C及空腹血糖(FBG)浓度均明显升高(P0.05);HDL-C浓度明显降低(P0.05);与纤维斑块组、钙化斑块组相比,软斑块组MCP-1、RANTES及Cys-C浓度均明显升高(P0.05);与钙化斑块组相比,纤维斑块组MCP-1、RANTES及Cys-C浓度均明显升高(P0.05);联合检测血清MCP-1、RANTES、Cys-C预测ACS患者,阳性准确率为89.2%,阴性准确率为92.5%,综合准确率为90.8%,明显高于单纯Hs-CRP的检测方法(P0.05)。结论:血清MCP-1、RANTES及Cys C联合检测对急性冠状动脉综合征的诊断效果优于单纯检测Hs-CRP。该联合检测方法具有一定的临床应用价值。     

The nature of the problem: an overview of acute coronary syndromes and myocardial infarction

The leading cause of death worldwide is coronary heart disease (CHD). This often presents with atherosclerotic plaque rupture, leading to a partial or complete obstruction of coronary artery flow, and resulting ischemia or infarction of myocardial tissue. There are risk factors which can predict CHD risk, and the treatment of some risk factors can reduce the likelihood of developing an acute coronary syndrome (ACS). While the incidence of CHD may be decreasing in the developed world, significant increases are projected in the developing world. In addition to the immediate adverse events associated with ACS, these patients have long-term increases in morbidity and mortality, which make the worldwide epidemic of CHD a leading public health issue.     

Uric acid levels are associated with endothelial dysfunction and severity of coronary atherosclerosis during a first episode of acute coronary syndrome

The role of serum uric acid in coronary artery disease has been extensively investigated. It was suggested that serum uric acid level (SUA) is an independent predictor of endothelial dysfunction and related to coronary artery lesions. However, the relationship between SUA and severity of coronary atherosclerosis evaluated via endothelial dysfunction using peripheral arterial tone (PAT) and the reactive hyperhemia index (RHI) has not been investigated during a first episode of acute coronary syndrome (ACS). The aim of our study was to address this point. We prospectively enrolled 80 patients with a first episode of ACS in a single-center observational study. All patients underwent coronary angiography, evaluation of endothelial function via the RHI, and SUA measurement. The severity of the coronary artery lesion was assessed angiographically, and patients were classified in three groups based on the extent of disease and Gensini and SYNTAX scores. Endothelial function was considered abnormal if RHI?<?1.67. We identified a linear correlation between SUA and RHI (R² =?0.66 P <?0.001). In multivariable analyses, SUA remained associated with RHI, even after adjustment for traditional cardiovascular risk factors and renal function. SUA was associated with severity of coronary artery disease. SUA is associated with severity of coronary atherosclerosis in patients with asymptomatic hyperuricemia. This inexpensive, readily measured biological parameter may be useful to monitor ACS patients.     

2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: comments from the Dutch ACS working group

On behalf of the Dutch ACS working group, we discuss multiple recommendations which have been implemented in the 2015 ESC guidelines for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation.     

血浆B 型脑钠肽对急性冠脉综合征的病情影响及预后评估

目的:探讨血浆B型脑钠肽(BNP)对急性冠脉综合征的病情影响及预后评估的作用,为临床实践提供参考.方法:分别对30例健康体检者(对照组)和81例ACS患者(观察组)检测其入院24小时内的血浆BNP浓度,并在住院一周内行冠状动脉造影术,检查病变的冠脉支数.结果:观察组的血浆BNP浓度高于对照(P＜0.01),病变动脉支数与BNP水平呈正相关(P＜0.01).结论:BNP是急性冠脉综合征发病的重要因素,其水平高低可反映病情的严重程度,是预测病情和预后的重要指标.临床上应有效的监测BNP水平,对正确诊断和有效治疗急性冠脉综合征具有重要的意义.     

Retinol binding protein 4 levels relate to the presence and severity of coronary artery disease

BackgroundThe previous studies have showed that serum retinol binding protein 4 (RBP4) levels increase in metabolic disorders which are closely associated with cardiovascular diseases (CVD). However, the human studies investigating the role of RBP4 in CVD are conflicted. Therefore, we aimed to evaluate the relationship between RBP4 with the presence and severity of coronary artery disease (CAD) in this study.Methods55 patients with presenting acute coronary syndrome (ACS) and 43 control subjects who had various cardiovascular risk factors with normal coronary artery on coronary angiography were included in this study. The serum RBP4 concentrations were measured using ELISA method, clinically and anatomically score models were used to assess the severity of coronary lesion.ResultsSerum RBP4 levels were significantly higher in patients with ACS compared to the without ACS (68.40 ± 47.94 mg/L vs. 49.46 ± 13.64 mg/L; p = 0.014). RBP4 was correlated with GENSINI and SYNTAX I score (r = 0.286 p = 0.034; r = 0.403 p = 0.002 respectively). However, there was no relationship between RBP4 and GRACE score.ConclusionsThe serum RBP4 levels increase in patients with CAD and its increased levels may be correlated with CAD severity.     

Likelihood of acute coronary syndrome in emergency department chest pain patients varies with time of presentation

ABSTRACT: BACKGROUND: There is a circadian and circaseptal (weekly) variation in the onset of acute coronary syndrome (ACS). The aim of this study was to elucidate whether the likelihood of ACS among emergency department (ED) chest pain patients varies with the time of presentation. METHODS: All patients presenting to the Lund ED at Skane University Hospital with chest pain or discomfort during 2006 and 2007 were retrospectively included. Age, sex, arrival time at the ED and discharge diagnose (ACS or not) were obtained from the electronic medical records. RESULTS: There was a clear but moderate circadian variation in the likelihood of ACS among presenting chest pain patients, the likelihood between 8 and 10 am being almost twice as high as between 6 and 8 pm. This was mainly explained by a variation in the ACS likelihood in females and patients under 65 years, with no significant variation in males and patients over 65 years. There was no significant circaseptal variation in the ACS likelihood. CONCLUSIONS: Our results indicate that there is a circadian variation in the likelihood of ACS among ED chest pain patients, and suggest that physicians should consider the time of presentation to the ED when determining the likelihood of ACS.