Increased Th1 activity in patients with coronary artery disease

BACKGROUND: Atherosclerotic lesions are mainly composed of macrophages and T lymphocytes. Specific T helper type 1 (Th1) cytokines and interferon gamma (IFN-gamma) inducible chemokines have been shown to be present in these lesions, modulating the local immunologic response. To explore whether this increase in Th1 activity could also be detected in circulating cells indicating a systemic activation, we studied the peripheral expression of Th1 cytokines and chemokines in patients with coronary artery disease and controls. METHODS AND RESULTS: Fifty patients with coronary artery disease (25 with unstable angina and 25 with stable angina) and 10 controls were studied. Serum interleukin (IL)-12 and IFN-gamma and the expression of IFN-gamma inducible chemokines IP-10, Mig and their receptor CXCR3 in peripheral cells were analyzed. Serum IL-12 and intracellular expression of IFN-gamma were significantly elevated in patients with unstable angina. An enhanced expression of IFN-gamma chemokines IP-10, Mig and CXCR3 in patients with stable angina was also observed. CONCLUSIONS: This study demonstrates an increased systemic inflammatory activity in patients with coronary heart disease with a predominant Th1 response, particularly in patients with unstable angina, suggesting an important role played by this polarization in plaque formation and rupture.     

Tissue factor, tissue factor pathway inhibitor and cytoadhesive molecules in patients with an acute coronary syndrome

The tissue factor plays a crucial role in initiating blood coagulation after plaque rupture in patients with acute coronary syndrome. It is abundant in atherosclerotic plaques. Moreover, P-selectin, some cytokines, endotoxin and immune complexes can stimulate monocytes and induce the tissue factor expression on their surface. The aim of the study was to compare plasma levels of the tissue factor, tissue factor pathway inhibitor, P-selectin, E-selectin and ICAM-1 in patients with acute myocardial infarction, unstable angina pectoris, stable coronary artery disease and normal control subjects. In addition, plasma levels of the tissue factor, tissue factor pathway inhibitor, P-selectin, E-selectin and ICAM-1 were measured in the blood withdrawn from the coronary sinus in a subgroup of patients with unstable angina pectoris and stable coronary artery disease in which the difference between concentrations in the coronary sinus and systemic blood was calculated. A significant increase in tissue factor pathway inhibitor plasma levels was detected in patients with acute myocardial infarction (373.3+/-135.1 ng/ml, p<0.01) and unstable angina pectoris (119.6+/-86.9 ng/ml, p<0.05) in contrast to the patients with stable coronary artery disease (46.3+/-37.5 ng/ml) and normal subjects (45.1+/-14.3 ng/ml). The plasma levels of tissue factor pathway inhibitor were significantly increased both in the coronary sinus and systemic blood in the patients with unstable angina pectoris. There was only a non-significant trend to higher plasma levels of the tissue factor in patients with acute myocardial infarction and unstable angina pectoris as compared to the patients with stable coronary artery disease and normal subjects, the values being 129.1+/-30.2 pg/ml, 130.5+/-57.8 pg/ml, 120.2+/-45.1 pg/ml and 124.9+/-31.8 pg/ml, respectively. Plasma levels of soluble P-selectin was only slightly, but non-significantly higher in patients with unstable angina pectoris and stable coronary artery disease (184.2+/-85.4 ng/ml and 201.6+/-67.9 ng/ml, respectively) than in patients with the acute myocardial infarction (157.4+/-88.4 ng/ml) or normal subjects (151.4+/-47.1 ng/ml). The difference in plasma levels of soluble ICAM-1 between the blood withdrawn from the coronary sinus and systemic circulation correlated significantly with the corresponding difference in plasma levels of soluble P-selectin and E-selectin. In conclusion, the tissue factor and the tissue factor pathway inhibitor play a crucial role in the initiation of arterial thrombosis. The tissue factor pathway inhibitor levels are increased both in the systemic blood and in the coronary sinus of patients with the acute coronary syndrome.     

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.     

血清IgE水平与冠心病的相关性分析

目的:探讨血清IgE水平与冠心病的相关性。方法:将我院收治的135例患者根据冠脉造影结果分为冠心病组(CHD)和非冠心病组(non-CHD),冠心病组根据临床症状分为稳定型心绞痛组(SAP)、不稳定型心绞痛组(UAP)和急性心肌梗死组(AMI),动脉堵塞程度用Gensini评分量化,采用SIMENS BNII全自动免疫散射比浊仪测定总IgE水平。比较CHD和non-CHD组患者及SAP、UAP和AMI组患者血清IgE水平的差异,并进一步分析血清IgE等级与冠心病Gensini积分的相关性。结果:non-CHD患者血清IgE水平(32.3(13.5,61)KU/L)明显低于CHD患者(69(26.4,169)KU/L)(P=0.001),UAP和AMI患者血清IgE水平(78.6(37.0,191.0)KU/L、118.5(75.3,148.1)KU/L)均显著高于SAP组(36.7(20.7,96.7)KU/L)(P=0.034和P=0.001),且多支血病变组患者血清IgE水平(67.2(30.9,249.0)KU/L)显著高于单支血管病变患者(34.6(18.1,59.0)KU/L)(P=0.039)。IgE水平根据四分位间距分为四个等级,随着IgE分级水平增加冠心病Gensini积分增加。结论:冠心病患者血清IgE水平升高,且与冠心病类型和血管堵塞程度都存在显著相关性,可能辅助冠心病的诊断及病情监测。     

尿微量蛋白联合血凝在冠心病诊断中的检测价值

目的:探讨尿微量蛋白联合血清纤维蛋白原在冠心病的诊断价值。方法:选取同期在我院治疗的24例稳定型心绞痛的患者,36例诊断为不稳定型心绞痛的患者和30例诊断为急性心肌梗死的患者,并选择同期30例来我院体检健康志愿者为对照组。分析以上4组患者发病时尿微量蛋白及血清纤维蛋白原的变化情况。结果:与对照组比,3个冠心病组的尿微量蛋白及血清纤维蛋白原的含量显著升高(P<0.05),与稳定型心绞痛组比,不稳定型心绞痛组的尿微量蛋白及血清纤维蛋白原的含量显著升高(P<0.05);与不稳定型心绞痛组比,急性心梗的尿微量蛋白及血清纤维蛋白原的含量显著升高(P<0.05)。3组病患的尿微量蛋白及血清纤维蛋白原之间呈正相关关系(r=0.852,P<0.05)。结论:心肌梗死和心绞痛患者尿微量蛋白及血清纤维蛋白原含量较健康成人含量高,提示尿微量蛋白及血清纤维蛋白原的含量有助于对心肌梗死和心绞痛的诊断,对急性心肌梗死的诊断价值较高。     

Elevated levels of matrix metalloprotein-3 in patients with coronary aneurysm: A case control study

BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of arterial aneurysms through increased proteolysis of extracellular matrix proteins. Increased proteolysis due to elevated matrix degrading enzyme activity in the arterial wall may act as a susceptibility factor for the development of coronary aneurysms. The aim of this study was to investigate the association between MMPs and presence of coronary aneurysms. METHODS: Thirty patients with aneurysmal coronary artery disease and stable angina were enrolled into study (Group 1). Fourteen coronary artery disease patients with stable angina were selected as control group (Group 2). MMP-1, MMP-3 and C-reactive protein (CRP) were measured in peripheral venous blood and matched between the groups. RESULTS: Serum MMP-3 level was higher in patients with aneurismal coronary artery disease compared to the control group (20.23 +/- 14.68 vs 11.45 +/- 6.55 ng/ml, p = 0.039). Serum MMP-1 (13.63 +/- 7.73 vs 12.15 +/- 6.27 ng/ml, p = 0.52) and CRP levels (4.78 +/- 1.47 vs 4.05 +/- 1.53 mg/l, p = 0.13) were not significantly different between the groups. CONCLUSION: MMPs can cause arterial wall destruction. MMP-3 may play role in the pathogenesis of coronary aneurysm development through increased proteolysis of extracellular matrix proteins.     

Abdominal fat and risk of coronary heart disease in patients with peripheral arterial disease

Objective: We investigated whether the presence of concomitant coronary heart disease (CHD) in patients with peripheral arterial disease (PAD) can be explained by intra‐abdominal fat accumulation and compared different measures of adiposity as predictors of CHD in patients with PAD. Research Methods and Procedures: Data were collected from patients enrolled in the Second Manifestations of ARTerial disease (SMART) study, an ongoing prospective cohort study of patients with manifest vascular disease or vascular risk factors at the University Medical Centre Utrecht. The current analysis includes 315 patients, mean age 59 ± 10 years, who had PAD with (n = 79) or without (n = 236) CHD. Parameters of adiposity were measured, and intra‐abdominal fat and subcutaneous fat were measured ultrasonographically. Metabolic syndrome was defined according to Adult Treatment Panel III. Results: The prevalence of metabolic syndrome was higher among patients with CHD (63%) than among patients without CHD (48%). All parameters of adiposity indicated more fat in patients with CHD, except for subcutaneous fat. Waist circumference was associated with 64% higher prevalence of CHD (confidence interval, 20% to 123%) per 1 standard deviation increase in waist circumference after adjustment for age and sex. The odds ratio for waist circumference remained virtually the same after additional adjustment for the components of the metabolic syndrome and smoking. Discussion: An increased waist circumference, a crude measure of intra‐abdominal fat, is associated with an increased risk of concomitant CHD in patients with PAD.     

糖化清蛋白、高敏C反应蛋白与冠心病临界病变患者冠脉斑块形态学特征的关系及对功能性心肌缺血的预测研究

摘要 目的：分析糖化清蛋白、高敏C反应蛋白与冠心病临界病变患者冠脉斑块形态学特征的关系及对功能性心肌缺血的预测价值。方法：选择自2020年1月至2022年6月我院经冠脉造影确诊的165例冠心病临界病变患者作为研究对象,分为不稳定型心绞痛组和稳定型心绞痛组。检测两组血清糖化清蛋白、高敏C反应蛋白表达水平,使用靶血管造影检测冠脉斑块形态学指标,Pearson相关性分析血清糖化清蛋白、高敏C反应蛋白与冠脉斑块形态学指标的关系,通过ROC曲线下面积（AUC）评价血清糖化清蛋白联合高敏C反应蛋白对功能性心肌缺血的预测价值。结果：不稳定型心绞痛组血清糖化清蛋白、高敏C反应蛋白表达水平均高于稳定型心绞痛组（P＜0.05）;不稳定型心绞痛组最小管腔直径、最小管腔面积均小于稳定型心绞痛组,直径狭窄率、管腔面积狭窄率、斑块面积均大于稳定型心绞痛组（P＜0.05）;在165例冠心病临界病变患者中,发生冠脉易损斑块53例;易损斑块组血清糖化清蛋白、高敏C反应蛋白表达水平均高于非易损斑块组（P＜0.05）;经Pearson相关性分析,冠心病临界病变患者血清糖化清蛋白、高敏C反应蛋白表达水平均与最小管腔直径、最小管腔面积呈负相关,与直径狭窄率、管腔面积狭窄率、斑块面积呈正相关（P＜0.05）;经ROC曲线分析,血清糖化清蛋白联合高敏C反应蛋白预测冠心病临界病变患者发生功能性心肌缺血的AUC为0.910。结论：糖化清蛋白、高敏C反应蛋白与冠心病临界病变患者冠脉斑块形态学特征密切相关,有助于评估冠脉斑块易损性,联合预测功能性心肌缺血的效能较好,值得临床予以重视应用。     

Diagnosis of Coronary Heart Diseases Using Gene Expression Profiling; Stable Coronary Artery Disease,Cardiac Ischemia with and without Myocardial Necrosis

Cardiovascular disease (including coronary artery disease and myocardial infarction) is one of the leading causes of death in Europe, and is influenced by both environmental and genetic factors. With the recent advances in genomic tools and technologies there is potential to predict and diagnose heart disease using molecular data from analysis of blood cells. We analyzed gene expression data from blood samples taken from normal people (n = 21), non-significant coronary artery disease (n = 93), patients with unstable angina (n = 16), stable coronary artery disease (n = 14) and myocardial infarction (MI; n = 207). We used a feature selection approach to identify a set of gene expression variables which successfully differentiate different cardiovascular diseases. The initial features were discovered by fitting a linear model for each probe set across all arrays of normal individuals and patients with myocardial infarction. Three different feature optimisation algorithms were devised which identified two discriminating sets of genes, one using MI and normal controls (total genes = 6) and another one using MI and unstable angina patients (total genes = 7). In all our classification approaches we used a non-parametric k-nearest neighbour (KNN) classification method (k = 3). The results proved the diagnostic robustness of the final feature sets in discriminating patients with myocardial infarction from healthy controls. Interestingly it also showed efficacy in discriminating myocardial infarction patients from patients with clinical symptoms of cardiac ischemia but no myocardial necrosis or stable coronary artery disease, despite the influence of batch effects and different microarray gene chips and platforms.     

Pregnancy-associated plasma protein A and proform eosinophilic major basic protein in the detection of different types of coronary artery disease

Kryptor system was proven to be a rapid, standard method for pregnancy-associated plasma protein A and proform eosinophilic major basic protein (PAPP-A/proMBP) complex detection in coronary artery disease (CAD). No age and/or gender differences in 51 controls and 110 stable coronary artery disease (SCAD) patients were found. SCAD patients did not differ from controls and no difference in PAPP-A/proMBP levels with regards to the number of affected vessels was found. In 21 unstable angina pectoris (UAP), in 35 without and 66 with ST elevation acute myocardial infarctions (NSTEMI, STEMI respectively) patients PAPP-A/proMBP levels were increased (P=0.004 and P<0.0005, respectively). PAPP-A/proMBP levels did not correlate with cardiac troponin I (cTnI) in STEMI and NSTEMI patients. PAPP-A/ proMBP increase was more frequent than cTnI (P=0.036) within the early phase of STEMI. In NSTEMI patients PAPP-A/proMBP positivity was present in 50 % of cTnI negative cases. Receiver operating characteristic (ROC) analysis revealed the highest diagnostic accuracy of PAPP-A/proMBP (0.919) in STEMI cTnI positive cases. The highest specificity/sensitivity PAPP-A/proMBP levels for particular acute coronary syndrome (ACS) types were 10.65-14.75 mIU/l. Combination of PAPP-A/proMBP with cTnI increases their diagnostic efficacy within the early phase of ACS. Our results suggest that PAPP-A/proMBP complex is involved in processes preceding vulnerable plaque development in ACS.     

The total peroxyl radical trapping potential in serum - an assay to define the stage of atherosclerosis

Lipid peroxides were identified among the factors that contribute to the atherosclerotic plaque formation in the arterial wall. We hypothesised that a correlation may exist between the content of antioxidant constituents in the serum and the gravity of atherosclerosis. To this purpose, we have determined the serum total peroxyl radical- trapping potential (TRAP), which is the combined capacity of all antioxidants to neutralize free radicals in serum and followed its variation in hyperlipemic animals in correlation with the stage of atherosclerosis. In addition, we compared TRAP values in the sera of coronary heart disease (CHD) patients, with or without type II diabetes mellitus. Results showed that after 18 weeks of hyperlipemic diet, the mean TRAP values measured in sera isolated from hyperlipemic hamsters exhibited an about 44% decrease, in good agreement with the increase of serum cholesterol and triglycerides. In the 3 groups of CHD patients, TRAP values decreased with about 10% in sera of stable angina patients, 20% in unstable patients, as compared with normal subjects. The lowest TRAP values were detected in the sera of patients with acute myocardial infarction. The results obtained for different experimental animals and for CHD patients sera indicate that the TRAP method, as adapted in our laboratory, is a reliable and reproducible assay, fit to be used in clinical studies as an ex vivo measurable parameter that correlates with the stage of the atherosclerosis.     

Toll-like receptor 4 expressions on peripheral blood monocytes were enhanced in coronary artery disease even in patients with low C-reactive protein

Toll-like receptors (TLRs) play important roles in the pathogenesis of atherosclerosis. On the other hand, serum high sensitivity C-reactive protein (hsCRP) is known as an independent coronary risk factor, but cardiovascular events do occur even in low hsCRP levels. We investigated whether the TLR4 expression levels on human peripheral blood monocytes were associated with serum hsCRP levels or the occurrence of coronary artery diseases (CAD). One hundred CAD patients and 100 non-CAD subjects were enrolled. There were 72 non-CAD subjects and 53 CAD patients with low serum hsCRP levels. Among the low-hsCRP subjects, the TLR4 expression levels were higher in CAD patients than in non-CAD subjects (P < 0.05, after being adjusted for other risk factors). Moreover, TLR4 expression levels in stable angina pectoris (SAP) patients were elevated compared with those in non-CAD subjects (P < 0.05), and those in acute coronary syndrome patients were higher than SAP patients even in low-hsCRP subjects (P < 0.01). In conclusion, the TLR4 expression levels on peripheral blood monocytes in CAD patients were higher than those in non-CAD subjects and correlated with disease activity, even in low-hsCRP subjects. The combined measurement of serum hsCRP and the TLR4 expression on peripheral blood monocytes, especially among low-hsCRP subjects, may become a new coronary risk marker.     

冠心病患者介入治疗前后血清IL-18、sCD40L 和hs-CRP 水平的 变化及其意义

目的:探讨冠心病患者血清白介素18(Interleukin-18,IL-18)、白细胞分化抗原40配体(CD40L)、及高敏C反应蛋白(hs-CRP)水平在经皮冠状动脉介入术治疗前后的变化和意义。方法:选择经冠状动脉造影确诊的冠心病患者85例,根据病变程度分为单支病变组(n=32)、双支病变组(n=28)和多支病变组(n=25),采用双抗体夹心ELISA法测定PCI术前术后血清IL-18、CD40L和hs-CRP水平。结果:血清IL-18水平测定结果:多支病变组高于双支病变组,双支病变组高于单支病变组;支架置入术后显著高于术前,差异均有统计学意义(P<0.01)。血清CD40L水平测定结果:多支病变组高于双支病变组和单支病变组,差异均有统计学意义(P<0.01),双支病变组与单支病变组间差异无统计学意义(P>0.05);支架置入术后较术前显著升高,差异有统计学意义(P<0.01)。血清hs-CRP水平测定结果:多支病变组高于双支病变组,双支病变组高于单支病变组;支架置入术后显著高于术前,差异均有统计学意义(P<0.01)。结论:冠心病患者血清IL-18、CD40L和hs-CRP与冠脉病变程度密切相关,介入治疗可使冠心病患者血清IL-18、CD40L和hs-CRP水平升高,监测血清中IL-18、CD40L和hs-CRP水平变化可了解治疗效果和炎症程度。     

Immune response to human embryonic stem cell-derived cardiac progenitors and adipose-derived stromal cells

Transplantation of allogeneic human embryonic stem cell-derived cardiac progenitors triggers an immune response. We assessed whether this response could be modulated by the concomitant use of adipose-derived stromal cells (ADSC). Peripheral blood mononuclear cells were collected from 40 patients with coronary artery disease (CAD) and nine healthy controls. Cardiac progenitors (CD15(+) Mesp1(+)) were generated as already reported from the I6 cell line treated with bone morphogenetic protein (BMP)-2. Adipose-derived stromal cells were obtained from abdominal dermolipectomies. We assessed the proliferative response of peripheral lymphocytes from patients and controls to cardiac progenitors cultured on a monolayer of ADSC, to allogeneic lymphocytes in mixed lymphocyte culture and to the T cell mitogen phytohemaglutin A in presence or absence of ADSC. Cardiac progenitors cultured on a monolayer of ADSC triggered a proliferation of lymphocytes from both patients and controls albeit lower than that induced by allogeneic lymphocytes. When cultured alone, ADSC did not induce any proliferation of allogeneic lymphocytes. When added to cultures of lymphocytes, ADSC significantly inhibited the alloantigen or mitogen-induced proliferative response. Compared to healthy controls, lymphocytes from patients presenting CAD expressed a decreased proliferative capacity, in particular to mitogen-induced stimulation. Adipose-derived stromal cells express an immunomodulatory effect that limits both alloantigen and mitogen-induced lymphocyte responses. Furthermore, lymphocytes from patients with CAD are low responders to conventional stimuli, possibly because of their age and disease-associated treatment regimens. We propose that, in combination, these factors may limit the in vivo immunogenicity of cardiac progenitors co-implanted with ADSC in patients with CAD.     

Lymphocyte DNA damage in patients with acute coronary syndrome and its relationship with severity of acute coronary syndrome

OBJECTIVE: The aim of this study was to investigate the association between lymphocyte DNA damage and acute coronary syndromes (ACS). METHODS: The study population contained 53 patients with ACS, 48 patients with stable angina and 35 voluntary healty subjects. DNA damage was assessed by alkaline comed assay in peripheral lymphocyte and plasma levels of total antioxidant capacity (TAC) were determined using a novel automated measurement method. RESULTS: In ACS patients, DNA damage was significantly higher than in patients with stable angina and control subjects (144+/-52 AU, 116+/-37, 68+/-34 AU; for three p<0.001, respectively). The TAC levels in patients with ACS were lower than the other groups (1.24+/-0.31 mmol Trolox equiv./l, 1.46+/-0.29 mmol Trolox equiv./l, p<0.05, respectively). DNA damage values in patients with acute miyocardial infarction were significantly higher than in patients with unstable angina (159.8+/-53.0 AU versus 131.8+/-48.4 AU; p<0.05, respectively). Lymphocyte DNA damage values in patients with ACS showed positive correlation with d-dimer (r=0.880, p<0.001) troponin I (r=538, p<0.001) and C-reactive protein (r=0.544, p<0.001) and negative correlation with TAC (r=-0.346, p=0.011). In multiple linear regression analysis, TAC (beta=-0.213, p=0.001) and d-dimer (beta=0.697, p<0.001) were independent predictors of DNA damage in patients with ACS. CONCLUSIONS:These findings indicate that lymphocyte DNA damage level increases in patients with ACS. Elevated DNA damage may be related with plaque instability and be useful for the identification of patients with acute coronary syndromes.     

Serum CD121a (Interleukin 1 Receptor,Type I): A Potential Novel Inflammatory Marker for Coronary Heart Disease

Inflammation is now believed to be responsible for coronary heart disease (CHD). This belief has stimulated the evaluation of various inflammatory markers for predicting CHD. This study was designed to investigate the association between four inflammatory cytokines (CD121a, interleukin [IL]-1β, IL-8, and IL-11) and CHD. Here, we evaluated 443 patients with CHD and 160 CHD-free controls who underwent coronary angiography. Cytokines were evaluated using flow cytometry, and statistical analyses were performed to investigate the association between cytokine levels and the risk of CHD. Patients with CHD had significantly higher levels of CD121a. The odds ratios for CHD according to increasing CD121a quartiles were 1.00, 1.47 [95% confidence interval (CI): 0.79–2.72], 2.67 (95% CI: 1.47–4.84), and 4.71 (95% CI: 2.65–8.37) in an age- and sex-adjusted model, compared to 1.00, 1.48 (95% CI: 0.70–3.14), 2.25 (95% CI: 1.10–4.62), and 4.39 (95% CI: 2.19–8.79) in a model that was adjusted for multiple covariates. A comparison of the stable angina, unstable angina, and acute myocardial infarction (AMI) subgroups revealed that patients with AMI had the highest CD121a levels, although IL-1β levels were similar across all groups. IL-8 levels were also increased in AMI patients, and IL-11 levels were higher in CHD patients than in non-CHD patients. Correlation analysis revealed a positive association between CD121a, IL-8, and the Gensini score. Together, the significant increase in CD121a levels among CHD patients suggests that it may be a novel inflammatory marker for predicting CHD.     

Polymorphisms in the NQO1, GSTT and GSTM genes are associated with coronary heart disease and biomarkers of oxidative stress

It was hypothesized that the presence of genetic polymorphisms that decrease activity of the detoxification enzymes glutathione-S-transferase (GST) and quinone oxido-reductase (NQO1) may contribute to heart disease and affect biomarkers of coronary health and oxidative stress. Sixty-seven patients with angiographically confirmed coronary heart disease (CHD) and 63 healthy controls were genotyped for polymorphisms in the GST isoforms Mu and Theta (GSTM and GSTT respectively) and NQO1. Participants' blood levels of homocysteine (Hcy), C-reactive protein (CRP), oxidized low density lipoprotein (LDL) and total antioxidant capacity (TAOX) were measured. TAOX levels were significantly lower in women than men (P < or = 0.001) and this finding was more marked in the control group (P < or = 0.001). Hcy levels were higher in CHD patients (P=0.003 vs. control) which was mostly attributed to female patients (P=0.034 case vs. control). GSTM polymorphisms were present with greater frequencies in CHD cases with the odds ratio (OR) for GSTM equal to 3.77 vs. control. CHD patients also have an increased incidence of both GSTM and GSTT null polymorphisms (OR=5.13). In contrast, NQO1 polymorphisms were protective in CHD patients (OR=0.18 vs. control), which when stratified for genotype was due to heterozygous individuals. Significantly higher C-reactive protein levels occurred in CHD patients with lower NQO1 activity (P=0.001), however, due to the large variations in CRP levels seen in CHD patients; the clinical importance of this difference is unclear. Smokers with the GSTM null polymorphism were more likely to have CHD than non-smokers expressing the GSTM null polymorphism (OR=3.54, P=0.079). We conclude that a lack of activity in the detoxification enzymes NQO1 and GSTM, and biomarker levels are strongly associated with coronary heart disease with sex as a mitigating factor.     

冠心病患者介入治疗前后血清IL-18、sCD40L和hs-CRP水平的变化及其意义

目的：探讨冠心病患者血清白介素18（Interleukin-18,IL-18）、白细胞分化抗原40配体（CD40L）、及高敏C反应蛋白（hs-CRP）水平在经皮冠状动脉介入术治疗前后的变化和意义。方法：选择经冠状动脉造影确诊的冠心病患者85例,根据病变程度分为单支病变组（n=32）、双支病变组（n=28）和多支病变组（n=25）,采用双抗体夹心ELISA法测定PCI术前术后血清IL-18、CD40L和hs-CRP水平。结果：血清IL-18水平测定结果：多支病变组高于双支病变组,双支病变组高于单支病变组;支架置入术后显著高于术前,差异均有统计学意义（P〈0.01）。血清CD40L水平测定结果：多支病变组高于双支病变组和单支病变组,差异均有统计学意义（P〈0.01）,双支病变组与单支病变组间差异无统计学意义（P〉0.05）;支架置入术后较术前显著升高,差异有统计学意义（P〈0.01）。血清hs-CRP水平测定结果：多支病变组高于双支病变组,双支病变组高于单支病变组;支架置入术后显著高于术前,差异均有统计学意义（P〈0.01）。结论：冠心病患者血清IL-18、CD40L和hs-CRP与冠脉病变程度密切相关,介入治疗可使冠心病患者血清IL-18、CD40L和hs-CRP水平升高,监测血清中IL-18、CD40L和hs-CRP水平变化可了解治疗效果和炎症程度。     

IL-17A facilitates platelet function through the ERK2 signaling pathway in patients with acute coronary syndrome

Background

Platelet aggregation mediated by inflammation played a critical role in the development of coronary heart diseases (CHD). Our previous clinical researches showed that Th17 cells and their characteristic cytokine IL-17A were associated with the plaque destabilization in patients with acute coronary syndrome (ACS). However, the potent effect of IL-17A on platelets-induced atherothrombosis remains unknown.

Methods and Results

In this study, we detected the plasma IL-17A levels and platelet aggregation in patients with stable angina (SA), unstable angina (UA), acute myocardial infarction (AMI) and chest pain syndrome (CPS). In addition, the markers of platelet activation (CD62P/PAC-1) and the mitogen-activated protein kinases (MAPKs) pathway were detected in platelets from ACS patients. We found that plasma IL-17A levels and platelet aggregation in patients with ACS (UA and AMI) were significantly higher than patients with SA and CPS, and the plasma IL-17A levels were positively correlated with the platelet aggregation (R = 0.47, P<0.01). In addition, in patients with ACS, the platelet aggregation, CD62P/PAC-1 and the phosphorylation of ERK2 signaling pathway were obviously elevated in platelets pre-stimulated with IL-17A in vitro. Furthermore, the specific inhibitor of ERK2 could attenuate platelet aggregation and activation triggered by IL-17A.

Conclusion

Our experiment firstly proved that IL-17A could promote platelet function in patients with ACS via activating platelets ERK2 signaling pathway and may provide a novel target for antiplatelet therapies in CHD.     

Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients

ObjectiveTo determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events.DesignCollaborative meta-analyses (systematic overviews).ResultsOverall, among these high risk patients, allocation to antiplatelet therapy reduced the combined outcome of any serious vascular event by about one quarter; non-fatal myocardial infarction was reduced by one third, non-fatal stroke by one quarter, and vascular mortality by one sixth (with no apparent adverse effect on other deaths). Absolute reductions in the risk of having a serious vascular event were 36 (SE 5) per 1000 treated for two years among patients with previous myocardial infarction; 38 (5) per 1000 patients treated for one month among patients with acute myocardial infarction; 36 (6) per 1000 treated for two years among those with previous stroke or transient ischaemic attack; 9 (3) per 1000 treated for three weeks among those with acute stroke; and 22 (3) per 1000 treated for two years among other high risk patients (with separately significant results for those with stable angina (P=0.0005), peripheral arterial disease (P=0.004), and atrial fibrillation (P=0.01)). In each of these high risk categories, the absolute benefits substantially outweighed the absolute risks of major extracranial bleeding. Aspirin was the most widely studied antiplatelet drug, with doses of 75-150 mg daily at least as effective as higher daily doses. The effects of doses lower than 75 mg daily were less certain. Clopidogrel reduced serious vascular events by 10% (4%) compared with aspirin, which was similar to the 12% (7%) reduction observed with its analogue ticlopidine. Addition of dipyridamole to aspirin produced no significant further reduction in vascular events compared with aspirin alone. Among patients at high risk of immediate coronary occlusion, short term addition of an intravenous glycoprotein IIb/IIIa antagonist to aspirin prevented a further 20 (4) vascular events per 1000 (P<0.0001) but caused 23 major (but rarely fatal) extracranial bleeds per 1000.ConclusionsAspirin (or another oral antiplatelet drug) is protective in most types of patient at increased risk of occlusive vascular events, including those with an acute myocardial infarction or ischaemic stroke, unstable or stable angina, previous myocardial infarction, stroke or cerebral ischaemia, peripheral arterial disease, or atrial fibrillation. Low dose aspirin (75-150 mg daily) is an effective antiplatelet regimen for long term use, but in acute settings an initial loading dose of at least 150 mg aspirin may be required. Adding a second antiplatelet drug to aspirin may produce additional benefits in some clinical circumstances, but more research into this strategy is needed.

What is already known on this topic

Antiplatelet therapy is effective for short term treatment of patients with suspected acute myocardial infarction and unstable anginaLong term treatment is beneficial for patients who have had a myocardial infarction, stroke, or transient ischaemic attackDaily aspirin doses of 75-325 mg are effective

What this study adds

Antiplatelet therapy protects against vascular events among patients with stable angina, intermittent claudication, and (if oral anticoagulants are unsuitable) atrial fibrillationAntiplatelet therapy can be started promptly during acute presumed ischaemic stroke and continued long termDaily aspirin doses of 75-150 mg seem to be as effective as higher doses for long term treatments (and clopidrogel is an appropriate alternative for patients with a contraindication to aspirin)Short term addition of a glycoprotein IIb/IIIa antagonist to aspirin prevents vascular events in patients having percutaneous coronary intervention and those with unstable angina but causes increased bleeding