Biochemical markers in acute coronary syndrome

For many years, cardiac markers have been used to assist cardiologists in the diagnosis and management of patients with cardiovascular disease. At first, enzyme activities of aspartate aminotransferase, lactate dehydrogenase and creatine kinase have been used in diagnosing patients with chest pain in order to differentiate those with acute myocardial infarction. In the field of cardiac markers, emphasis is currently put on the use of protein markers such as myoglobin, and cardiac troponin T or I. Troponins are very highly cardiac specific and their concentration in blood increase only from four to six hours after the onset of chest pain. Today we obligatorily use two markers, the first being the early one (myoglobin, isoform of creatine kinase), which is very sensitive and shows up in the circulation one to two hours after myocardial damage. Confirmation of myocardial damage can be obtained by definite markers (troponin I or T), which are highly specific of myocardial damage.     

The association of serum neutrophil markers and acute coronary syndrome

An association exists between chronic infection-induced inflammation, such as periodontitis, and acute coronary syndrome (ACS). We studied the association of serum neutrophil markers, myeloperoxidase (MPO), matrix metalloproteinase (MMP)-8, tissue inhibitor of metalloproteinase (TIMP)-1 concentrations and MMP-8/TIMP-1 ratio, with the risk of recurrent ACS. Radiographic periodontal status was recorded from 141 patients with acute non-Q-wave infarction or unstable angina pectoris, who participated in a double-blind, placebo-controlled study with clarithromycin for 3 months. Serum samples were collected within arrival to the hospital, at 1 week, 3 months and 1 year. Recurrent ACS events were registered during the 1-year follow-up. In the whole population, high serum MPO concentrations at 1 week (fourth quartile versus quartiles 1-3) were associated with the risk of recurrent ACS with a relative risk (RR) of 2.52 (95% CI, 1.277-4.980; P = 0.008). In patients without periodontal disease, high MPO concentration at 1 week and 1 year predicted recurrent ACS with RRs of 3.54 (1.600-7.831; P = 0.002) and 2.87 (1.171-7.038; P = 0.021), respectively. In the placebo group, but not in the clarithromycin group, high serum MMP-8/TIMP-1 ratio at 1 week predicted recurrent ACS with an RR of 3.23 (1.295-8.063; P = 0.012). Our results suggest that high serum neutrophil markers reflect increased risk of recurrent ACS, especially in patients without periodontal disease and not receiving antimicrobial medication.     

Arrhythmia in acute coronary syndrome

Specific features of most common arrhythmias and cardiac conduction disorders found in patients with acute coronary syndrome are described. The review is intended for physicians properly informed on the general principles of the diagnosis and treatment of cardiac arrhythmias, as a differentiated concise guideline on approaching these patients.     

Changes of monocyte subsets in patients with acute coronary syndrome and correlation with myocardial injury markers

Objective: To explore the changes of peripheral blood monocytes subsets in acute coronary syndrome (ACS) and its clinical significance. Methods: A total of 68 ACS patients and 27 healthy subjects (HS) were enrolled. Monocyte subset analysis was performed using flow cytometry: CD14++CD16-(Mon1), CD14++CD16+ (Mon2), and CD14+CD16++ (Mon3). Results: 1. The number of Mon1 and Mon3 were significantly increased in ACS patients compared with HS (P<0.05) and Mon2 decreased in ACS patients (P<0.05). 2. The number of Mon1, Mon2, Mon3 was positively correlated with WBC count (P<0.05). The Mon2% was negatively correlated with the serum levels of LDH, CK, CK-MB (P<0.05). The number of Mon1, Mon3 was positively correlated with the serum levels of LDH, CK, CK-MB (P<0.05). Conclusion: The changes in different subsets of monocytes may be associated with pathogenesis of ACS and myocardial injury. The findings might be useful in the assessment of myocardial injury.     

微颗粒与急性冠脉综合征

Coronary heart disease (CHD) is an important cause of death in the world. Among them, acute coronary syndrome (ACS) is a type of CHD that has a high mortality rate. Microparticles (MPs) are tiny particles formed in the process of cell activation and apoptosis, carrying specific markers of their mother cells. There is more and more evidence that MPs derived from endothelial cells, platelets, white blood cells and other cells are closely related to the formation of ACS. Through a variety of pathways, they take part in endothelial cell damage, vascular dysfunction, plaque erosion and rupture, and thrombosis. The findings of MPs enrich our knowledge about ACS, and may provide a new approach to the treatment of ACS.     

Clinical morphology of acute coronary syndrome

The paper describes acute coronary syndrome and gives its definition, classification and current possibilities of its clinical and morphological diagnosis. Emphasis is laid on the troponine test and clinicoinstrumental imaging of coronary arterial obstruction and myocardial ischemia. Data on the morphological criteria for vulnerable atherosclerotic plaque, different stages of ischemia and early myocardial necrosis are presented. Recommendations on establishing the postmortem diagnosis of acute coronary syndrome are given.     

白介素-18与急性冠状动脉综合征

动脉粥样硬化斑块的不稳定导致冠心病特殊疾病谱——急性冠状综合征的发生。炎症机制在动脉粥样硬化斑块的发生、发展中扮演重要角色。近年来，不断有研究证实前炎症因子白介素-18密切参与了此过程，并且与急性冠状动脉综合征的发生有着极强的关联。     

Antithrombotic treatment of acute coronary syndrome

After we have become aware that arteriosclerosis provokes thrombotic and thromboembolic process, which is the most common cause of occlusion of coronary arteries, in the past 30 years significant improvements have been made in antithrombotic treatment of acute coronary syndrome. Antithrombotic therapy of acute coronary syndrome has been explored in few directions. These are thrombolytic multidrug therapy, anticoagulant therapy with nonfractional and low molecular heparin, therapy with glycoprotein IIb/IIIa receptor antagonists and antiaggregation therapy with acetylsalicylic acid and tienopyrid. Research results and clinical experience point to a conclusion that antithrombotic therapy is the cornerstone in the mariagement of acute coronary syndrome. In this paper, results of major studies and main antithrombotic treatment guidelines in acute coronary syndrome accepted by international professional associations are presented.     

Antianginal and antiadrenergic therapy in acute coronary syndrome

In recent years cardiology has opened new chapters in the treatment of acute coronary syndrome (ACS). The acute therapeutic procedures include antianginal, anticoagulant and revascularization therapy. Optimal therapeutic procedure in ACS has two objectives: 1) quick removal of the factors causing ischemia, and 2) prevention of death or myocardial infarction, i.e. reinfarction. Nitrates have been present in pharmacotherapy for more than 150 years. They are used exclusively to efficiently suppress the symptoms, but there is no proof of their positive effect on the disease prognosis. The effect of nitrates is manifested as vasodilatation in the arterial, and particularly in the venous vascular basin (central and peripheral effects) thus increasing the capacity of venous blood. Besides the peripheral effect, nitrates have an important central effect, i.e. they dilate epicardial coronary arteries, both the healthy ones and those damaged by atherosclerosis, in this way increasing the collateral blood circulation. Organic nitrates, although the oldest antianginal drug, play one of the leading roels in the treatment of ACS even today. Beta-adrenergic blocking agents have been used since 1960 in the treatment of arterial hypertension, coronary disease and cardiac arrhythmias, and later their efficacy in the prevention of secondary myocardial infarction was noted. Beta blockers (BB) reduce heart rate, systemic blood pressure and myocardial oxygen requirements, reduce myocardial contractility, thus alleviating precordial pain in ACS, decreasing the rate of threatening infarction, and reducing ventricular arrhythmias. Numerous clinical studies have shown that BB in ACS improve the disease prognosis and play an important role in long-term secondary prevention after myocardial infarction. Antagonists of calcium channel blockers are a group of therapeutic agents successfully used in numerous cardiac and noncardiac indications. Potential benefits of calcium antagonists in ACS are the result of various combinations, such as dilation of coronary arteries and arterioles, reduction of heart rate and myocardial oxygen requirements, and beneficial effect on left ventricular function and elasticity. The use of calcium channel blockers in ACS reduces or prevents the symptoms and accompanying ischemia, but there is no evidence that these agents prolong survival in patients with heart failure. In recent years the treatment of an ACS has significantly changed owing to better understanding of the pathogenesis of the disease as well as progress in medicinal and interventional treatment. Antianginal therapy, which includes nitrates analgesics, calcium channel blockers and antiadrenergic therapy using beta-blockers in treatment of ACS, takes a significant place.     

Myocardial revascularization strategy in patients with acute coronary syndrome

Acute coronary syndrome (ACS) represents a spectrum of conditions caused by activated malignant coronary disease, with one of the following outcomes: stabilization, myocardial infarction or sudden death. The strategies of diagnostic procedures and treatment for ACS have been developed on the basis of differentiation between the two main groups of patients: those with unstable angina pectoris (UAP) and non-ST-segment elevation myocardial infarction (NSTEMI), and those with ST-elevation myocardial infarction (STEMI). The diagnosis and treatment of STEMI patients have both temporal and spatial limitations, where rapid identification and use of revascularization strategy, generally from 6 to not more than 12 hours, are the mainstay of the respective algorithm. In contrast to this, in UAP/NSTEMI patients the nature of the disease usually allows for more time for the diagnosis and choice of most appropriate therapy, whereas the chance of saving practically the entire myocardial area is much greater. Proposals of the possible algorithms for the procedures to be used in the diagnosis and management of ACS, based on the real possibilities available in the Republic of Croatia, and some our own results are presented in this review.     

Prognostic value of telomere length in acute coronary syndrome

Telomere and telomerase are involved in cellular and organismal ageing and have been related to human diseases. Coronary artery disease is one of the most common age-related health problems in developed countries. Nevertheless, the specific role of cellular ageing in this process is still unclear. In this study, we analyze the possible prognostic value of telomere length and telomerase polymorphisms in a population of 150 middle aged males (mean age 62 ± 7) admitted for acute coronary syndrome who were followed up for more than 600 days. Peripheral blood samples were obtained and relative and comparative qPCR was used to measure telomere length and real time PCR to study the polymorphisms. Two prognostic combined events were defined. Long telomere length was revealed as an independent predictor (protector) of combined event presentation during long term follow up in our patients.     

Argatroban in HIT type II and acute coronary syndrome

Prior to initiation of the ARG-911 and ARG-915 clinical trials, there was no optimal replacement for heparin anticoagulation in patients with heparin-induced thrombocytopenia (HIT) type II. These prospective, historical controlled studies were designed to determine the usefulness of argatroban, a direct thrombin inhibitor (DTI) that is not immunogenic and does not interact with heparin antibody, in answering this clinical need. Clinical outcomes (37-day period) for 568 argatroban-treated and 193 control patients demonstrated significantly reduced risks of the primary efficacy composite endpoint (all-cause death, all-cause amputation, new thrombosis) and the secondary endpoints (death due to thrombosis, new thrombosis) with argatroban. Argatroban patients also experienced a more rapid recovery of platelet count. Bleeding events were similar among both groups. It was concluded that argatroban anticoagulation, compared with historical controls, improves clinical outcomes without increasing bleeding risk in patients having HIT with or without thrombosis. Argatroban has since been approved in the US for both prophylaxis and treatment of thrombosis in patients with HIT. Argatroban has been used in percutaneous coronary interventions in patients with and without HIT, for peripheral vascular procedures in both large and small vessels in HIT patients, and as an adjunct to thrombolytic therapy for the treatment of AMI. Treatment success rates and the same or less bleeding was demonstrated with argatroban compared to heparin controls. These pilot studies suggest that argatroban will provide reliable anticoagulation during interventional procedures. A consistent safety profile of argatroban has been demonstrated in all studies to date. The main attributes of argatroban are its rapid onset of action, fast reversibility of its anticoagulant effect, inhibition of clot-bound thrombin, easily monitored by the aPTT and ACT and no dosage adjustment in renal-impaired individuals. These properties make argatroban a predictable and useful anticoagulant for HIT and non-HIT patients.     

Periodontopathogen- and host-derived immune response in acute coronary syndrome

Owing to molecular mimicry, periodontal pathogen carriage may result in a systemic cross-reactive immune response with the host. The analyses were performed to investigate if serum antibody levels to human heat shock protein 60 (HSP60) are associated with the antibody levels and salivary carriage of two periodontal pathogens, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, as well as with the dental status in patients with acute coronary syndrome (ACS). ACS patients (n = 141) were monitored at baseline when entering to hospital, and after 1 week, 3 months and 1 year. Periodontal status was recorded by dental radiographs, and A. actinomycetemcomitans and P. gingivalis were detected by PCR from saliva at baseline. Serum IgG and IgA antibody levels were determined at all time points. All antibody levels remained quite stable during the follow-up. Serum IgG-class antibody levels to A. actinomycetemcomitans and HSP60 had a strong positive correlation with each other at all time points (r～0.4, P < 0.05). Mean serum IgG antibody levels to HSP60 were significantly higher in the A. actinomycetemcomitans IgG- and IgA-seropositive than in the seronegative patients, but did not differ between the pathogen carriers compared to the non-carriers. HSP60 antibody levels did not differ significantly between the edentulous, non-periodontitis and periodontitis patients. Despite the observed cross-reactivity in the systemic IgG-class antibody response to HSP60 and A. actinomycetemcomitans, the pathogen carriage in saliva or the periodontal status did not affect the HSP60 antibody levels in ACS patients.     

血清同型半胱氨酸水平测定对急性冠脉综合征患者的临床意义

目的 测定急性冠脉综合征（ACS）患者血清中同型半胱氨酸（Hcy）的水平,探讨血清Hcy水平对ACS患者的临床意义.方法 入选2010年5月至2012年12月本院住院65例ACS患者,其中不稳定型心绞痛（UA）33例、急性心肌梗死（AMI）32例,同时入选稳定性心绞痛（SA）35例,并以32例健康体检者作为阴性对照组,测定各组血清Hcy水平,进行统计学分析.结果 血清Hcy水平,UA组（18.15±4.72）μmol/L、AMI组（21.62±5.56） μmol/L、SA组（16.03±3.16）μmol/L、对照组（9.86±2.53） μmol/L,UA及AMI组明显高于SA组及对照组（P＜0.05）;且AMI组显著高于UA组,各组间差异有统计学意义（P＜0.05）.结论 血清Hcy水平升高为ACS的危险因素,可作为反映ACS病情的指标.