The utility of inflammation and platelet biomarkers in patients with acute coronary syndromes

Introduction

Thrombotic and inflammatory mechanisms are involved in the pathophysiology of acute coronary syndrome (ACS). The aim of the study was the evaluation of inflammation (white blood cells count/WBC, C-reactive protein/CRP, interleukin-6/IL-6) and platelet (platelet count/PLT, mean platelet volume/MPV, large platelet/LPLT, beta-thromboglobulin/β-TG) biomarkers in the groups of ACS patients depending on the severity of signs and symptoms and compared to controls without coronary artery disease.

Thrombosis, physical activity, and acute coronary syndromes

Acute coronary syndromes (ACS) are common, life-threatening cardiac disorders that typically are triggered by rupture or erosion of an atherosclerotic plaque. Platelet deposition and activation of the blood coagulation cascade in response to plaque disruption lead to the formation of a platelet-fibrin thrombus, which can grow rapidly, obstruct coronary blood flow, and cause myocardial ischemia and/or infarction. Several clinical studies have examined the relationship between physical activity and ACS, and numerous preclinical and clinical studies have examined specific effects of sustained physical training and acute physical activity on atherosclerotic plaque rupture, platelet function, and formation and clearance of intravascular fibrin. This article reviews the available literature regarding the role of physical activity in determining the incidence of atherosclerotic plaque rupture and the pace and extent of thrombus formation after plaque rupture.     

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.     

Effects of Helicobacter pylori eradication on platelet activation and disease recurrence in patients with acute coronary syndromes

BACKGROUND: Platelet activation is consistently observed in animal models of Helicobacter pylori infection and could help to explain the alleged epidemiological association between H. pylori and coronary heart disease. MATERIALS AND METHODS: Ninety-two patients with recent acute coronary syndromes were enrolled. Helicobacter pylori-positive patients were randomized to receive a 7-day course of omeprazole, amoxycillin and metronidazole or placebos. Two months later, H. pylori status was reassessed and baseline parameters, including soluble P-selectin and platelet surface expression of CD62P, CD63 and CD41, were measured again. Patients were followed-up for 1 year or until death or readmission. RESULTS: No baseline differences were observed between H. pylori-positive and -negative cases. Among H. pylori-positive patients, 18 received placebo and 31 received active medication resulting in eradication in 21 cases. No differences were observed in inflammatory parameters or platelet activation markers between patients with persistent or resolved H. pylori infection. However, coronary events recurred at 6 and 12 months, respectively, in 35% and 55% of patients with persisting H. pylori infection compared with 10% and 25% of patients in whom H. pylori was either absent or eradicated (p = .01). Only final H. pylori status [RR 3.07 (95% CI 1.35-98)] and number of coronary risk factors [RR 2.58 (95% CI 1.51-4.41)] were independent predictors of recurrence. CONCLUSIONS: Infection with H. pylori does not induce significant platelet activation in patients treated for coronary disease. Helicobacter pylori-infected patients, however, may have an increased risk of recurrence of coronary events.     

Revascularization in the acute coronary syndromes

Coronary heart disease is the leading cause of death worldwide, and occurs when the coronary arteries are unable to supply adequate oxygenated blood to the myocardium, which in turn can lead to ischemia and infarction of myocardial tissue. There are three options for revascularization in the setting of acute coronary syndromes. In select patients, coronary artery bypass surgery remains an option. Thrombolytics were initially the mainstay of therapy, which has now shifted to angioplasty, with or without stents, when readily available. Revascularization has been demonstrated to improve patient outcomes, and has evolved rapidly in the recent past.     

Decreased plasma nociceptin/orphanin FQ levels after acute coronary syndromes

Foregoing researches made on the N/OFQ system brought up a possible role for this system in cardiovascular regulation. In this study we examined how N/OFQ levels of the blood plasma changed in acute cardiovascular diseases. Three cardiac patient groups were created: enzyme positive acute coronary syndrome (EPACS, n = 10), enzyme negative ACS (ENACS, n = 7) and ischemic heart disease (IHD, n = 11). We compared the patients to healthy control subjects (n = 31). We found significantly lower N/OFQ levels in the EPACS [6.86 (6.21-7.38) pg/ml], ENACS [6.97 (6.87-7.01) pg/ml and IHD groups [7.58 (7.23-8.20) pg/ml] compared to the control group [8.86 (7.27-9.83) pg/ml]. A significant correlation was detected between N/OFQ and white blood cell count (WBC), platelet count (PLT), creatine kinase (CK), glutamate oxaloacetate transaminase (GOT) and cholesterol levels in the EPACS group.Decreased plasma N/OFQ is closely associated with the presence of acute cardiovascular disease, and the severity of symptoms has a significant negative correlation with the N/OFQ levels. We believe that the rate of N/OFQ depression is in association with the level of ischemic stress and the following inflammatory response. Further investigations are needed to clarify the relevance and elucidate the exact effects of the ischemic stress on the N/OFQ system.     

不同剂量普伐他汀对急性冠状动脉综合症血脂及vWF因子的影响

目的：探讨不同剂量普伐他汀对早期急性冠状动脉综合症患者血脂及血浆vWF水平的影响。方法：将120例冠状动脉综合症患者随机分为：常规治疗组（30例）和普伐他汀治疗组（90例）。常规治疗组采用阿司匹林、硝酸酯类、血管紧张素转换酶抑制剂等,普伐他汀治疗组是在常规治疗基础上加用普伐他汀,按照普伐他汀的剂量又分为：10mg/d、20mg/d和40mg/d三组,持续用药4周。检测治疗前后患者的hs-CRP、HDL-C、LDL-C、TC、TG与vWF等因子水平的变化。选取30例健康人作为对照组。结果：与正常组或常规治疗组相比,急性冠状动脉综合症患者治疗4周后,普伐他汀组中患者的hs-CRP、LDL-C、HDL-C、TC、TG与vWF因子的水平变化的差异均有统计学意义（P＆lt;0.05）。在普伐他汀使用的三个剂量中,以20mg/d治疗组的治疗效果相对最好（P＆lt;0.05）,副作用相对较小。结论：常规药物联合中等剂量的普伐他汀治疗早期急性冠状动脉综合症可获得良好的疗效,且安全性高,值得推广。     

Differences in admission rates and outcomes between men and women presenting to emergency departments with coronary syndromes

Background

Previous studies examining sex-related differences in the treatment of coronary artery disease have focused on patients in hospital. We sought to examine sex-related differences at an earlier point in care — presentation to the emergency department.

Methods

We collected data on ambulatory care and hospital admissions for 54 134 patients (44% women) who presented to an emergency department in Alberta between July 1998 and March 2001 because of acute myocardial infarction, unstable angina, stable angina or chest pain. We used logistic regression and Cox regression analyses to determine sex-specific associations between the likelihood of discharge from the emergency department or coronary revascularization within 1 year and 1-year mortality after adjusting for age, comorbidities and socioeconomic factors.

Results

Following the emergency department visit, 91.3% of patients with acute myocardial infarction, 87.4% of those with unstable angina, 40.7% of those with stable angina and 19.8% of those with chest pain were admitted to hospital. Women were more likely than men to be discharged from the emergency department: adjusted odds ratio (and 95% confidence interval [CI]) 2.25 (1.75–2.90) for acute myocardial infarction, 1.71 (1.45–2.01) for unstable angina, 1.33 (1.15–1.53) for stable angina and 1.46 (1.36–1.57) for chest pain. Women were less likely than men to undergo coronary revascularization within 1 year: adjusted odds ratio (and 95% CI) 0.65 (0.57–0.73) for myocardial infarction, 0.39 (0.35–0.44) for unstable angina, 0.35 (0.29–0.42) for stable angina and 0.32 (0.27–0.37) for chest pain. Female sex had no impact on 1-year mortality among patients with acute myocardial infarction; it was associated with a decreased 1-year mortality among patients with unstable angina, stable angina and chest pain: adjusted hazard ratio (and 95% CI) 0.60 (0.46–0.78), 0.60 (0.46–0.78) and 0.74 (0.63–0.87) respectively.

Interpretation

Women presenting to the emergency department with coronary syndromes are less likely than men to be admitted to an acute care hospital and to receive coronary revascularization procedures. These differences do not translate into worse outcomes for women in terms of 1-year mortality.For patients experiencing a new-onset acute cardiac event, the emergency department is usually the point of first contact with the health care system. A fraction of patients presenting to the emergency department are admitted to an acute care hospital for treatment or continued observation. Given that decisions made in the emergency department govern not only immediate but also longer-term treatment and outcomes, it is imperative that these decisions be appropriate.The issue of gender bias in the treatment and outcomes of coronary artery disease has been examined extensively. The current guidelines of the American College of Cardiology and American Heart Association state that the treatment of acute coronary syndromes in women should be no different from that in men.^1,2 However, several studies have found evidence to the contrary. There is general consensus that the frequency of cardiac catheterization is lower among women and that they undergo fewer revascularization procedures.^3–11 Whether these lower rates are due to an inherent gender bias or indicate appropriate care continues to be debated.Most studies of gender bias in cardiovascular care have focused either on patients in an acute care facility or on selected patient populations, such as those who have undergone cardiac catheterization. The few studies that have examined sex-specific differences in treatment decisions earlier in the process of care (i.e., in the emergency department) have either been single-centre studies¹² or have involved clinical trial patients.¹³ Moreover, examination of sex-specific differences in cardiac care has traditionally been limited to more acute conditions, such as acute myocardial infarction and unstable angina.^{5,10,11,14–21} There is a need to expand our evaluation to a wider spectrum of coronary syndromes. We undertook the current study (a) to examine differences in rates of admission to acute care hospitals between men and women presenting to the emergency department with a main ambulatory care diagnosis of acute myocardial infarction, unstable angina, stable angina or chest pain and (b) to determine whether a patient''s sex is an independent predictor of 1-year treatment and outcomes in this cohort of patients.     

The relationship between trace elements and cardiac markers in acute coronary syndromes

Previous studies have demonstrated increased serum copper and iron levels and decreased selenium and zinc levels in patients with myocardial infarction. Furthermore, the prognostic value of the levels of trace elements in myocardial infarction has been stressed. We examined serum levels of Cu, Fe, Zn and Se, as well as glutathione peroxidase (GPx), a selenoenzyme with antioxidant properties, and C-reactive protein (CRP), a marker of inflammation, in acute coronary syndromes (ACS) regarding their relationship to cardiac troponins and creatine kinase-MB mass (CK-MBm), important prognostic markers. Serum trace elements, GPx activity and CRP were determined in 70 patients with ACS who were admitted within 12 h after the onset. Differences in these parameters were evaluated in three groups of patients divided according to the levels of cardiac markers: group III consisted of patients with high increases in cTnT, cTnI and CK-MBm (> or =0.9 ng/mL, > or =1.0 ng/mL, > or =30 ng/mL, respectively), patients with milder increases in these markers were included in groups II and I consisted of patients with values just above the upper reference limits. Serum Fe levels increased significantly in group II and even more prominently in group III compared to group I (p = 0.04, 0.002, respectively). There was no significant difference between groups II and III. The increase in serum Cu was significant in group III compared to both groups II and I (p = 0.04, 0.001, respectively). There was no significant difference between groups I and II regarding Cu and Zn. The decrease in serum Se and GPx levels was significant only between groups III and I (p = 0.004 for Se and p = 0.0001 for GPx). CRP levels showed a significant increase in group III compared to groups II and I (p = 0.03 and 0.001). CRP showed a significant positive and GPx a significant negative correlation to the cardiac markers cTnT, cTnI and CK-MBm. Cu was positively correlated to all cardiac markers, while the positive correlation between Fe and cardiac markers was significant only for cTnI. Both Zn and Se were negatively correlated to cTnT, and Se was also to cTnI. In conclusion, the increase in serum levels of Cu and Fe and the decrease in serum levels of Zn and Se in patients with higher levels of troponins and CK-MBm imply that trace element levels are related to the degree of myocardial damage and thus may play a role in the pathogenesis of ischemic heart disease. The strong correlations between cardiac markers and both CRP and GPx suggest that these parameters are promising prognostic factors in acute coronary syndromes.     

Platelet aggregation and antiplatelet agents in acute coronary syndromes

Antiplatelet agents are the cornerstone therapy of acute coronary syndromes. In the setting of ST elevation myocardial infarction, antiplatelet therapy prevent the prothrombotic effect of reperfusion therapy including thrombolysis and primary percutaneous coronary intervention. In non ST-elevation acute coronary syndromes, antiplatelet therapy prevent s complete coronary thrombotic occlusion and therefore the occurrence of ST elevation myocardial infarction. Antiplatelet agent benefit is related to the patient's risk profile. It is well established that combined antiplatelet therapy is the most effective in high risk patients. Several important issues have to be faced including the identification of non responders, dose adjustment and the management of temporary interruption of antiplatelet agents in stable coronary artery disease patients.     

C-Reactive protein reactions to glucose-insulin-potassium infusion and relations to infarct size in patients with acute coronary syndromes

Little is known about preoperative predictors of resource utilization in the treatment of high-risk patients with severe symptomatic aortic valve stenosis. We report results from the prospective, medical-economic “TAVI Calculation of Costs Trial”. In-hospital resource utilization was evaluated in 110 elderly patients (age ≥ 75 years) treated either with transfemoral (TF) or transapical (TA) transcatheter aortic valve implantation (TAVI, N = 83), or surgical aortic valve replacement (AVR, N = 27). Overall, 22 patient-specific baseline parameters were tested for within-group prediction of resource use. Baseline characteristics differed between groups and reflected the non-randomized, real-world allocation of treatment options. Overall procedural times were shortest for TAVI, intensive care unit (ICU) length of stay (LoS) was lowest for AVR. Length of total hospitalization since procedure (THsP) was lowest for TF-TAVI; 13.4 ± 11.4 days as compared to 15.7 ± 10.5 and 21.2 ± 15.4 days for AVR and TA-TAVI, respectively. For TAVI and AVR, EuroScore I remained the main predictor for prolonged THsP (p <0.01). Within the TAVI group, multivariate regression analyses showed that TA-TAVI was associated with a substantial increase in THsP (55 to 61 %, p <0.01). Additionally, preoperative aortic valve area (AVA) was identified as an independent predictor of prolonged THsP in TAVI patients, irrespective of risk scores (p <0.05). Our results demonstrate significant heterogeneity in patients baseline characteristics dependent on treatment and corresponding differences in resource utilization. Prolonged ThsP is not only predicted by risk scores but also by baseline AVA, which might be useful in stratifying TAVI patients. German Clinical Trial Register Nr. DRKS00000797     

Role of plaque inflammation in acute and recurrent coronary syndromes

Inflammation plays an important role in the initiation, development, progression and complications of atherosclerotic vascular disease. Our present knowledge of the elementary role of inflammation for the onset of plaque rupture in atherosclerotic coronary lesions primarily stems from autopsy studies. However, the introduction of directional coronary atherectomy catheters has provided a unique opportunity to directly investigate the role of inflammation in coronary syndromes. In this report we describe the role of coronary plaque inflammation, as determined by immunohistochemistry, on the presentation of coronary syndromes and on the clinical outcome following percutaneous interventions.     

Vitamin E modulation of C-reactive protein in smokers with acute coronary syndromes

Acute coronary syndromes are characterized by the expression of proinflammatory cytokines such as C-reactive protein (CRP). Sustained upregulation of inflammatory markers is associated with an adverse prognosis. Vitamin E is known to have significant anti-inflammatory properties and has been associated with a reduction in cardiovascular events in some studies of high-risk patients. The mechanism of benefit remains controversial. We conducted a randomized, double-blind placebo controlled trial of vitamin E 400 IU daily for 6 months in 110 patients with acute coronary syndromes. Serum samples were collected at enrollment and at 2, 4, and 6 months. CRP, interleukin-6 and the soluble cell adhesion molecules were measured. Vitamin E levels increased significantly in the treatment group (from 31 micromol/l at baseline to 51 micromol/l, p <.0001) and were unchanged in the placebo group (32 micromol/l at baseline to 34 micromol/l, p = NS). CRP levels fell in both the vitamin E group and the placebo group over the treatment period (from 17.2 +/- 2.9 to 6.1 +/- 0.8 mg/l and from 21.5 +/- 4.9 to 5.9 +/- 0.9 mg/l, p = NS for the difference between active and placebo groups). However, vitamin E treatment was associated with significantly lower 6 month CRP levels in smokers versus smokers on placebo (4.7 +/- 0.71 mg/l vs. 8.26 +/- 1.5 mg/l, p =.02). Vitamin E reduces CRP levels in smokers with acute coronary syndromes for up to 6 months after hospitalization.