Troponins in acute coronary syndromes

Delivering superior clinical specificity and sensitivity for myocardial necrosis, cardiac troponin has replaced creatine kinase-MB as the preferred biomarker for establishing the diagnosis of myocardial infarction. On the basis of expert recommendations, present convention sets the diagnostic decision-limit for each assay at the 99th percentile of troponin levels in an apparently healthy reference population. Owing to a lack of standardization between different assays, this level, corresponding to the 99th percentile, will vary depending upon the manufacturer. Among patients presenting with an acute coronary syndrome (ACS), even low-level elevations of cardiac troponin T or I are associated with higher risk of death and recurrent ischemic events compared with patients with a troponin level below the appropriate decision limit. Renal failure does not appear to diminish the prognostic value of troponins among patients with a high clinical probability of ACS. In addition, patients with elevated levels of troponin appear to gain the most benefit from more aggressive medical therapy with antithrombin and antiplatelet medications as well as an early invasive management strategy. Cardiac troponins offer extremely high tissue specificity but do not discriminate between ischemic and nonischemic mechanisms of myocardial injury; thus, presently the clinician must assess whether a patient's presenting symptoms are consistent with ACS. It is possible that future generations of troponin assays will detect specific post-translational modifications of troponins that may increase the analytic sensitivity for myocardial damage and offer insight into the timing and mechanism of myocardial injury.     

Troponins in patients with acute coronary syndromes: biologic,diagnostic, and therapeutic implications

The cardiac troponins have expanded the spectrum of detectable myocardial injury and enhanced the clinician's ability to identify patients with acute coronary syndromes who are at higher risk for death or recurrent ischemic events. Based on available data, it appears most likely that any reliably detected troponin elevation results from myocyte necrosis. This notion has served as the basis for the recent revision of diagnostic criteria for acute myocardial infarction based on cardiac troponin. Nevertheless, further research is necessary to conclusively refute the possibility that the release of cardiac troponins may also occur in the setting of reversible myocyte injury resulting from cellular ischemia. Such an investigation establishing biologic correlates of troponin elevation is likely to prove valuable in guiding diagnostic terminology as well as in therapy. For example, clinical research finding cardiac troponin elevation to be predictive of intracoronary throumbus and distal microvascular obstruction has been important to the evaluation of troponis for targeting powerful antiplatelet and antithrombin therapies. Whether related to irreversible or reversible injury, the cardiac troponins have blurred the traditional boundaries between unstable angina and myocardial infarction and have evolved as powerful tools for risk stratification and therapeutic decision-making.     

Inflammation in acute coronary syndromes

Extensive evidence supports a pathogenic role for both local and systemic inflammation in acute coronary syndromes. However, several important questions remain unanswered. Is the observed inflammatory process a precursor or a consequence of coronary plaque rupture? Is the inflammatory component of unstable coronary disease a potential therapeutic target? Finally, do infectious agents have a pathogenic role in coronary atherosclerosis and acute coronary syndromes?     

Echocardiography in acute coronary syndromes

Echocardiography including 2 Dimensional, Color Doppler, Tissue Doppler Imaging, Myocardial Contrast Echocardiography, Strain and Strain rate, etc are the most powerful modalities for the assessment of myocardial performance in patients with established orsuspected acute coronary syndrome and acute myocardial infarction with a high accuracy, sensitivity and specificity. Dobutamine Stress Echocardiography has tremendous potential of evaluating microcirculation impairment especially in diagnosing the extent of myocardial damage, reversibility component at rest and at the peak levels of stress with appropriate drugs, mechanical (percutaneous coronary intervention) or surgical intervention. Echocardiography and its newer modalities are therefore, promising and valuable tools for assessment of myocardial perfusion in the setting of myocardial infarction. This article provides an overview of clinical evidence supporting the efficacy of echocardiography and its newer modalities in assessment of myocardial function and performance. Timely effective evaluation of acute coronary syndrome and myocardial infarction by echocardiography and its newer modalities may help in early diagnosis,prognositification and warrant specific therapeutic intervention, thereby help in reducing morbidity and mortality.     

Statins in acute coronary syndromes

Statins are the main resource available to reduce LDL-cholesterol levels. Their continuous use decreases cardiovascular morbidity and mortality due to atherosclerosis. The administration of these medications demonstrated to be effective in primary and secondary prevention clinical trials in low and high risk patients. Specialists believe that a possible benefit of hypolipidemic therapy in preventing complications of atherosclerotic diseases is in the reduction of deposition of atherogenic lipoproteins in vulnerable areas of the vasculature. Experimental studies with statins have shown an enormous variety of other effects that could extend the clinical benefit beyond the lipid profile modification itself. Statin-based therapies benefit other important components of the atherothrombotic process: inflammation, oxidation, coagulation, fibrinolysis, endothelial function, vasoreactivity and platelet function. The demonstration of the effects that do not depend on cholesterol lowering or the pleiotropic effects of statins provides the theoretical basis for their potential role as adjunctive therapy in acute coronary syndromes. Retrospective analyses of a variety of studies indicate the potential benefit of statins during acute coronary events. Recent clinical studies have addressed this important issue in prospective controlled trials showing strong evidence for the administration of statins as adjunctive therapy in acute coronary syndromes.     

Hirudin in acute coronary syndromes

Acute coronary syndromes are a major cause of morbidity and mortality in Western societies. The term describes a spectrum from unstable angina, the recently defined non-Q wave infarction (the Non ST-Elevation Myocardial Infarction [NSTEMI]), to acute transmural myocardial infarction. With regard to treatment, a series of recently published studies compared the specific direct thrombin inhibitor hirudin with standard unfractionated heparin. Initial small studies showed promising results and led to the initiation of large-scale clinical trials addressing patients with acute coronary syndromes. However, in these studies, an unacceptably high incidence of serious hemorrhagic complications prompted safety boards to stop trials. In those studies carried out according to the protocol, no significant clinical benefit of hirudin over standard heparin was proved. Here, hirudin has been shown to be equivalent to unfractionated heparin for the treatment of unstable coronary syndromes with or without ST elevation and as an adjunct to percutaneous coronary balloon angioplasty. Because of its narrow therapeutic window between clinical benefit and increased bleeding hazards, hirudin should be used cautiously. For patients with heparin-induced thrombocytopenia, hirudin is accepted as an important therapeutic alternative.     

Glycemia in acute coronary syndromes

Diabetes is an established major factor of poor prognostis after an acute coronary syndrome. Recent studies have addressed the impact of abnormal glucose metabolism at the acute phase in patients without known diabetes. It has been found that abnormal glycemia regulation is more common than normal regulation in patients presenting with acute coronary syndrome, whatever the method used to evaluate blood glucose metabolism. High blood glucose at admission, whether fasting or not, are associated with worse outcome after an acute coronary syndrome, i.e. by increased mortality and development of severe heart failure. The prognosistic value of glycemia is valuable for both short and long term outcomes. Admission glycemia measurement allows therapeutic strategies at the acute phase. Fasting glycemia and oral glucose tolerance test performed during the hospital stay discloses valuable diagnostic information and provide useful tools for secondary prevention. Moreover, fasting glycemia is a more powerful predictor for short term outcome after myocardial infarction than admission glycemia. The mechanisms by which hyperglycemia deteriorates the cardiovascular prognosis, in particular for left ventricular dysfunction, are not fully understood. Stress hyperglycemia may be a marker of extensive cardiac damage, reflecting a surge of stress hormones such as catecholamines and cortisol that participate to insulinresistance and affect fatty acid and glucose homeostasis. Recent findings also argue for a direct deleterious effect of hyperglycemia on myocardium.     

Cytokines in acute coronary syndromes

The aim of this study was to show the presence of an imbalance between pro-inflammatory and anti-inflammatory mediators in patients affected by acute coronary syndromes (ACS). We evaluated the production in cultured and stimulated lymphomonocytes of interferon (IFN)gamma and tumor necrosis factor (TNF)alpha, which are well known to possess pro-inflammatory effects, and of interleukin (IL)10, which has been shown to have a protective anti-inflammatory activity, in two groups of 30 patients affected by acute myocardial infarction (AMI) and unstable angina (UA), compared with two equivalent groups of patients with stable angina (SA) and of healthy volunteers. We found a significant increase of IFNgamma and TNFalpha production (p<0.01) and a significant decrease of IL-10 production (p<0.01) in cultures of lymphomonocytes taken from patients with AMI and UA compared with SA patients and controls. No significant changes were found between AMI and UA patients and SA patients and controls. We conclude that a relevant imbalance in cytokine release is present in ACS, markedly favoring pro-inflammatory effects.     

Anticoagulant agents in acute coronary syndromes

There has been substantial interest in novel antiplatelet therapies; yet, despite a growing number of studies with novel anticoagulants, there have been few comprehensive reviews summarizing the data for anticoagulants in acute coronary syndromes. Large-scale trials have demonstrated the efficacy of novel procedural anticoagulants, such as selective Factor-Xa inhibitors and direct thrombin inhibitors. Moreover, with as many as 10% of patients with non-ST-segment elevation acute coronary syndrome experiencing recurrent ischemia or death in the first 30 days, there is continued interest in oral anticoagulants. The purpose of this review is to synthesize the evidence for current anticoagulants, including heparins and more recent Factor Xa inhibitors and direct thrombin inhibitors, as well as oral anticoagulants and newer agents in later phases of clinical testing.     

Marijuana use in acute coronary syndromes

Background: Cannabis is one of the most widely used illicit substances worldwide, and it has the highest prevalence among drugs used in Egypt. Objectives: The aims were to evaluate whether the use of cannabis is a risk factor of acute coronary heart disease in low-risk, young males and to compare the cardiac pathological changes between cannabis exposed and non-exposed ischemic patients. Methods: This was a cross-sectional study that was performed on 138 male patients, aged ≤ 40 years, with acute myocardial infarction who were admitted to the Cardiac Care Unit at the University Hospital. Urine samples were submitted for toxicological analysis using a homogenous enzyme immunoassay technique to determine the substance of use. The patients were divided into three groups: group 1 (n = 23), cannabis-positive only patients; group 2 (n = 28), patients positive for any other substance of use; and group 3 (n = 34), patients negative for any substance of use. Results: Smoking was prominent, whereas group 1 had no other risk factors. In groups 1 and 2, ST-segment elevation myocardial infarction (STEMI) was dominant, whereas no ST-segment elevation myocardial infarction (NSTEMI) was prominent in group 3. Ischemic resting wall motion abnormalities were presented in 47.8% of group 1 and in only 11.8% of group 3. None of group 1 had normal coronaries, whereas 14.3% of group 3 had normal coronaries. Significant changes in echocardiography and angiography were observed between group 1 and other groups. Conclusion: Cannabis smoking could be a potential risk factor for the development of cardiac ischemia.     

Immune response in acute coronary syndromes

Inflammatory response in the atherosclerotic lesions of coronary artery disease, mediated by cellular immune mechanisms is well appreciated. The significance of the immuno-inflammatory processes for the development of acute ischaemic sequelae of these lesions remains unsettled. Fifty patients of acute coronary syndromes were studied for complement components and immunoglobin levels by single radial immunodiffusion method. Twenty-eight patients of acute myocardial infarction showed significantly lower levels of complement components C3 and C4 at admission (C3--69.19 +/- 12.91 mg% compared to 82.40 +/- 9.26 mg% in controls, p < 0.01; C4--14.56 +/- 2.46 mg% compared to 18.53 +/- 2.69 mg% in controls, p < 0.01). Twenty-two patients of unstable angina did not show any significant change (C3--83.14 +/- 8.01 mg% and C4--19.07 +/- 4.47 mg%). Sixteen patients of acute myocardial infarction who were thrombolysed with streptokinase showed a steep rise in the levels of complement components immediately after thrombolysis (C3--69.19 +/- 12.91 mg% before and 100.56 +/- 17.09 mg% after thrombolysis, p < 0.001; C4--14.56 +/- 2.46 mg% before and 21.48 +/- 4.78 mg% after thrombolysis, p < 0.001). Plasma C3 and C4 levels in acute myocardial infarction showed no relationship with peak CPK levels. Plasma immunoglobulins remained unchanged in patients of acute coronary syndromes.     

Tissue factor in acute coronary syndromes

Thrombosis at the site of atherosclerotic plaque disruption is the principal cause of acute coronary syndromes. The severity of the clinical consequences is determined by the extent and the progression of the thrombus that are caused by local and systemic factors. In atherosclerotic lesions mediators induce tissue factor (TF) in macrophages, smooth muscle cells, and endothelial cells. Procoagulant microparticles in the lipid core further enhance the thrombogenicity of the plaque. In addition, in acute coronary syndromes circulating monocytes and microparticles express TF and, thereby, contribute to systemic procoagulant activity. As a regulatory mechanism surface-bound, endogenous tissue factor pathway inhibitor-1 (TFPI) inhibits TF activity by translocation of the quaternary complex TF-FVIIa-FXa-TFPI into glycosphingolipid-rich microdomains more efficiently than exogenously added TFPI. This inhibition occurs not only in endothelial cells but also on circulating monocytes and presumably microparticles. Because therapeutic thrombolysis in acute myocardial infarction degrades TFPI, a prothrombotic state due to unopposed TF activity may occur. Several studies have demonstrated a contribution of local and bloodborne TF to thrombus formation; a direct relationship with the clinical outcome, however, awaits further studies. This article discusses the current understanding of the role of TF and its regulation by TFPI in acute coronary syndromes.     

Dysglycemia in suspected acute coronary syndromes

BACKGROUND: Apart from diabetes itself, even minor glycometabolic dysregulation may be associated with an increased risk of cardiovascular disease. We analyzed the prevalence and predictive value of glycometabolic disturbances in patients with a suspected acute coronary syndrome (ACS). METHODS: In a prospective follow-up study, admission glucose and Hba1C levels in all consecutive patients with suspected ACS were measured. Dysglycemia was defined as a Hba1C of 5.6-6.1% with a non-fasting glucose above 7.8 mmol/L. Both predictors of glycometabolic disturbances and the predictive value of glycometabolic disturbances were studied. RESULTS: Of the 521 patients with a suspected ACS who were included in the study, 332 (64%) had an ACS and 189 (36%) had atypical chest pain. A total of 115 patients (22%) had diabetes and 65 (13%) had dysglycemia. Patients with diabetes or dysglycemia had an increased risk of a confirmed diagnosis of ACS (RR 2.3, 95% CI 1.5-3.4). Multivariate analyses did not change these findings. CONCLUSIONS: One in three patients with suspected ACS had a glucose metabolism disturbance. Glycometabolic disturbance was strongly associated with a confirmed diagnosis of ACS. Whether intensive treatment of patients with disturbed glucose metabolism may improve long-term prognosis needs to be assessed.     

Ethnic variations in acute coronary syndromes

Although it is very likely that ethnic variations in the incidence and, possibly, clinical outcome of acute coronary artery disease events exist, the causes for such differences are many and difficult to address fully, given the complex interplay of contributing factors.