新型心肌损伤标志物在胸痛患者早期诊断中的应用

急性冠状动脉综合征是一类心脏突发缺血性综合征。目前临床广泛使用的传统心肌损伤标志物如肌钙蛋白等在特异性、灵敏度以及信号时效性等方面存在局限性,致使急性胸痛患者误诊、漏诊或延误治疗而错过最佳抢救治疗时机。为此,研究人员近年来研究发现一些针对急性冠状动脉综合征患者具有早期诊断预测价值的新型心肌损伤标志物。本文将针对这些新型心肌损伤标志物在急性冠状动脉综合征患者早期诊断应用中的研究进展进行综述。     

急性冠状动脉综合征生物标志物的研究现状

随着冠心病发病率的逐年升高,人们对急性冠状动脉综合征生物标志物的研究也不断深入.目前临床上常用于诊断急性冠状动脉综合征的生物标志物有肌红蛋白、肌酸激酶同工酶、肌钙蛋白、高敏肌钙蛋白等.越来越多的生物标志物被发现可用于急性冠状动脉综合征的早期诊断、风险分层和预后评估.目前研究发现的心脏生物标志物按其产生机制和生理效应分为...     

Acute coronary syndrome: biochemical strategies in the troponin era

New biomarkers, such as cardiac troponins, have a major role to play for cost-effective management of individuals with acute chest pain and suspected coronary syndrome, and the laboratory is now poised to assume a vital role in assessing damage and determining prognosis. The redefined biochemical criterion proposed to classify acute coronary syndrome patients presenting with ischemic symptoms as patients with myocardial infarction is heavily predicated on an increased troponin concentration in blood. In an era of evidence-based medicine, we can no longer overlook the diagnostic and prognostic benefits provided by the measurement of these highly sensitive and specific proteins.     

Biomarkers in acute coronary syndrome and percutaneous coronary intervention

The universal definition of myocardial infarction has proved how important the role of biomarkers in the assessment of acute coronary syndrome (ACS) has become. As a result, management of patients with ACS today is more specific and personalized than ever, but there is still a lot of room for improvement. Unmet needs for a faster and more specific rule-in and rule-out of myocardial infarction, for a pronounced risk assessment allowing for standardized guidelines on personalized therapy and for an effective monitoring of our therapeutic efforts to guarantee an optimal risk-benefit turnout still require intensive biomarker research and clinical validation. This review addresses a set of cardiovascular biomarkers with different pathophysiological backgrounds and discusses their diagnostic, prognostic and therapeutic value in the setting of ACS and percutaneous coronary intervention (PCI). The article provides a review of the current knowledge and literature on biomarkers in ACS and PCI, discussing currently used biomarkers like cardiac troponin (cTN), high sensitive cardiac troponin (hscTn), natriuretic peptides (NPs) as well as promising future biomarkers like copeptin, choline and lipoprotein-associated phospholipase A2 (LP-PLA2). The review concentrates on the clinical application of these markers, evaluating not only their diagnostic and prognostic value but also their integrability into routine practice. There are currently a number of new biomarkers and new biomarker assays under investigation which give hope for a much improved diagnostic and risk stratification process. Large diagnostic clinical trials are still needed to evaluate their impact on ACS patient management and subsequent PCI in clinical practice.     

Cardiovascular outcome in hospitalized patients with minimal troponin I elevation and normal creatine phosphokinase

BACKGROUND: Among patients with acute coronary syndrome, elevated cardiac troponin and creatine phosphokinase MB fraction levels have both prognostic and diagnostic values. However, in hospitalized patients, cardiac biomarkers are measured in a variety of clinical situations including but not limited to acute coronary syndrome. Moreover, these patients may have elevated troponin levels with no increase in creatine phosphokinase MB fraction levels. OBJECTIVE: To evaluate the cardiovascular outcome of acutely ill, hospitalized patients with minimal troponin I increase with normal creatine phosphokinase MB fraction. METHODS: We identified 64 patients retrospectively from our database with minimal troponin I increase and normal creatine phosphokinase MB fraction hospitalized between November 1998 and April 2000. Discharged patients were questioned about re-hospitalization for myocardial infarction, unstable coronary syndrome, congestive heart failure and percutaneous coronary intervention by means of a structured questionnaire. For those patients who died during hospitalization, data were collected from hospital records. For patients who died at home or at a different institution, a surviving relative completed the questionnaire. Primary outcomes were death, myocardial infarction and the need for revascularization or re-hospitalization. RESULTS: Composite endpoint of death, myocardial infarction, percutaneous coronary intervention or coronary artery bypass grafting and re-hospitalization for cardiac cause occurred in 35.95% of patients within 1 year. CONCLUSIONS: There is a significant composite event rate of death, myocardial infarction or re-hospitalization for cardiac causes in acutely ill, hospitalized patients with normal creatine phosphokinase MB fraction and minimally elevated troponin I, regardless of the cause for hospitalization.     

Troponin in Cardiovascular Disease Prevention: Updates and Future Direction

Cardiac troponin has been well described as the preferred biomarker for diagnosis of myocardial infarction due to the high sensitivity and specificity for myocardial injury. Numerous other conditions apart from acute coronary syndrome can also lead to small elevations in troponin levels. However, the use of cTn as prognostic biomarker for the primary assessment of cardiovascular risk in asymptomatic patient has only recently been described. And with the development of newer generations of high-sensitivity cardiac troponin assays that can detect 10-fold lower concentrations of troponin, the potential value cTn in the prevention and management of asymptomatic cardiovascular disease has come to the fore. This review provides an overview of the transition of cardiac troponin as a marker of acute myocardial injury to one that detects sub-clinical injury. Evidence continues to show that high-sensitivity troponin is emerging as one of the most powerful prognostic biomarkers for the assessment of cardiovascular risk in the general population.     

Human heart-type fatty acid-binding protein as an early diagnostic and prognostic marker in acute coronary syndrome

Although heart-type fatty acid-binding protein (H-FABP) can be a marker of sarcolemmal injury due to acute myocardial ischemia, the diagnostic or prognostic value is not established in patients with acute chest pain. This multicenter prospective study aimed to determine the diagnostic and prognostic values of H-FABP in 133 patients presenting to an emergency room with suspected acute coronary syndrome (ACS) by comparing with those of conventional biomarkers. H-FABP and myoglobin had greater positive results than did creatine kinase-MB or troponin T. Receiver operating characteristics analysis revealed that H-FABP was the most reliable for detection of ACS and that H-FABP had the greatest sensitivities for identification of patients requiring emergency hospitalization, coronary angiography, and interventional therapy within 7 days among the biomarkers. Thus, H-FABP can be an early diagnostic and prognostic biochemical marker, particularly within the first 6 h from the onset of chest symptoms, in patients with chest pain at an emergency department.     

超敏肌钙蛋白在急性冠状动脉综合征中的临床应用

急性心肌梗死的早期诊断和及时进行再灌注治疗为降低死亡率的关键,故对因急性胸痛就诊的患者进行快速、正确的评估以及危险分层尤为重要;而评估心肌坏死的特异性生化标记物为急性心肌梗死诊断、监测病程与评价预后的主要指标之一。近期发展的超敏肌钙蛋白(hsTn)的检测技术可更精确地测定肌钙蛋白(cTn)的浓度并可检测99%健康人群以上的异常值,其不仅可提高急性心肌梗死的诊断率,亦可进一步进行危险分层,可用于急性冠状动脉综合征患者的长期风险评估。     

Cardiac troponin T in acute coronary syndrome with renal insufficiency

Cardiac troponin levels are frequently elevated in patients with chronic renal failure, hence diagnosis of myocardial necrosis is difficult. The prevalence of elevated serum troponin T was determined and its diagnostic value in acute coronary syndrome was assessed in patients with chronic renal insufficiency. A retrospective cross-sectional analysis was performed in 227 patients with chronic renal insufficiency and a diagnosis of unstable angina, non-ST or ST-segment elevation myocardial infarction. All patients had baseline serum troponin T levels measured at previous visits; the baseline troponin T level was raised in 53.3%. Cardiac troponin T levels did not correlate with creatinine levels, and were not affected by dialysis. Mortality after an acute coronary event was high (46.3%). Because of the elevated baseline cardiac troponin T levels, detection of acute coronary syndrome in patients with chronic renal failure requires evaluation of serial cardiac enzyme measurements and serial 12-lead electrocardiograms. Early and definitive cardiac interventions may contribute towards decreasing the mortality rate in this group of patients.     

Use and misuse of cardiac troponins in clinical practice

Cardiac troponins are very sensitive and specific markers of myocardial injury. Elevated troponin levels in the setting of acute coronary syndrome are diagnostic of acute myocardial infarction and provide guidance to clinicians with regard to appropriate use of intensive medical and revascularization therapies. However, elevated troponin levels are commonly seen in several noncoronary ischemia presentations and create considerable confusion among clinicians in these settings. In this review article, we discuss the utility of troponins in various clinical settings and present a "common sense" approach to interpreting troponin elevation outside the setting of acute coronary syndrome.     

Novel biomarkers for cardiovascular risk prediction

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. The primary prevention of CVD is dependent upon the ability to identify high-risk individuals long before the development of overt events. This highlights the need for accurate risk stratification. An increasing number of novel biomarkers have been identified to predict cardiovascular events. Biomarkers play a critical role in the definition, prognostication, and decision-making regarding the management of cardiovascular events. This review focuses on a variety of promising biomarkers that provide diagnostic and prognostic information. The myocardial tissue-specific biomarker cardiac troponin, high- sensitivity assays for cardiac troponin, and heart-type fatty acid binding proteinall help diagnose myocardial infarction (MI) in the early hours following symptoms. Inflammatory markers such as growth differentiation factor-15, high-sensitivity C-reactive protein, fibrinogen, and uric acid predict MI and death. Pregnancy-associated plasma protein A, myeloperoxidase, and matrix metalloproteinases predict the risk of acute coronary syndrome. Lipoprotein-associated phospholipase A2 and secretory phospholipase A2 predict incident and recurrent cardiovascular events. Finally, elevated natriuretic peptides, ST2, endothelin-1, mid-regional-pro-adrenomedullin, copeptin, and galectin-3 have all been well vali?dated to predict death and heart failure following a MI and provide risk stratification information for heart failure. Rapidly developing new areas, such as assessment of micro-RNA, are also explored. All the biomarkers reflect different aspects of the development of atherosclerosis.     

Outcomes of hospitalized patients with non-acute coronary syndrome and elevated cardiac troponin level

Objective

Cardiac troponin levels help risk-stratify patients presenting with an acute coronary syndrome. Although cardiac troponin levels may be elevated in patients presenting with non-acute coronary syndrome conditions, specific diagnoses and long-term outcomes within that cohort are unclear.

Methods

By using the Veterans Affairs centralized databases, we identified all hospitalized patients in 2006 who had a troponin assay obtained during their initial reference hospitalization. On the basis of the diagnostic codes of the International Classification of Diseases, 9th Revision, primary diagnoses were categorized as acute coronary syndrome or non-acute coronary syndrome conditions.

Results

Of a total of 21,668 patients with an elevated troponin level who were discharged from the hospital, 12,400 (57.2%) had a non-acute coronary syndrome condition. Among that cohort, the most common diagnostic category involved the cardiovascular system, and congestive heart failure (N = 1661) and chronic coronary artery disease (N = 1648) accounted for the major classifications. At 1 year after hospital discharge, mortality in patients with a non-acute coronary syndrome condition was 22.8% and was higher than in the acute coronary syndrome cohort (odds ratio 1.39; 95% confidence interval, 1.30-1.49). Despite the high prevalence of cardiovascular diseases in patients with a non-acute coronary syndrome diagnosis, use of cardiac imaging within 90 days of hospitalization was low compared with that in patients with acute coronary syndrome (odds ratio 0.25; 95% confidence interval, 0.23-0.27).

Conclusions

Hospitalized patients with an elevated troponin level more often have a primary diagnosis that is not an acute coronary syndrome. Their long-term survival is poor and justifies novel diagnostic or therapeutic strategy-based studies to target the highest risk subsets before hospital discharge.     

Troponins in acute coronary syndromes

Cardiac troponins have replaced creatine kinase-MB as the preferred biomarker for establishing the diagnosis of myocardial infarction (MI). Expert recommendations set the diagnostic decision-limit for each assay at the 99th percentile of troponin levels in an apparently healthy reference population, which due to a lack of standardization, 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 correlate with higher risk of death and recurrent ischemic events compared to patients with levels of troponin below the decision limit. Renal failure does not appear to diminish the prognostic value of troponins among patients with a high clinical probability of ACS. Moreover, patients with elevated levels of troponin derive the most benefit from more intense medical therapy with antithrombin and antiplatelet medications, as well as an early invasive management strategy. Whereas cardiac troponins are extremely specific for myocardial necrosis, they do not discriminate between ischemic and non-ischemic etiologies of myocardial injury. Clinicians must, therefore, determine whether a patient's presenting symptoms are consistent with ACS. Combining troponin with other cardiac biomarkers may offer complimentary information on the underlying pathobiology and prognosis in an individual patient. Future generations of troponin assays may detect specific posttranslational modifications of troponins that may increase the analytic sensitivity for myocardial damage and offer insight into the timing and mechanism of myocardial injury.     

An Update on Cardiac Troponins as Circulating Biomarkers in Heart Failure

Circulating troponins and natriuretic peptides are the only biomarkers specifically released from cardiac myocytes that can be determined with robust and sensitive analytical methods, even in healthy subjects. These intracellular proteins are released from reversibly or irreversibly damaged cardiac myocytes into the bloodstream by mechanisms that are not entirely clear. The recent introduction of a new generation of highly sensitive assays of cardiac troponin I or T has not only improved the early diagnosis of acute myocardial infarction but also suggested that there are several causes for troponin release other than acute coronary syndromes. Circulating troponins are elevated in patients with acute or chronic heart failure and are strongly associated with outcome, independently of natriuretic peptides, the benchmark biomarkers in heart failure. In the absence of further experimental evidences, the pathophysiologic basis for the elevation of circulating cardiac troponins in patients with stable chronic heart failure remains speculative.     

La troponine et les autres marqueurs de souffrance myocardique,quelle signification en médecine interne ?

PURPOSE: Troponin is now the gold standard for the diagnosis of myocardial infarction. Aiming at improving the management of a patient suspect of an acute coronary syndrome, this article will point the interpretation of troponin dosages according to the clinical presentation and concomitant diseases. ACTUALITIES: First, the interest of troponin dosage as compared with other markers of myocardial ischemia will be underlined. Then, the literature available about troponin in cardiovascular diseases but also in extracardiac diseases will be analysed. Finally, the difficulties of assay will be discussed. PERSPECTIVES: The availability of a sensitive and specific marker such as troponin is definitively a progress in the management of patients with an acute coronary syndromes. But it remains a biological contribution to the global management of the patient. It is important to know the causes susceptible to increase the levels of troponin to avoid a wrong interpretation of the dosage, leading to diagnostic but also therapeutic mistakes.     

Biomarcadores no troponínicos,complementarios, alternativos y presuntos,para el síndrome coronario agudo: nuevos recursos para los futuros instrumentos de cálculo del riesgo

Biomarkers, other than cardiac troponin, with potential sensitivity and selectivity that provide diagnostic and prognostic insights into the tissue–specific injury processes underlying acute coronary syndrome and their possible use in risk stratification algorithms are discussed. Such biomarkers may be useful as complementary or alternative to cardiac troponin (I or T) assays in early diagnosis of acute coronary syndrome, as well as for monitoring acute coronary syndrome progression and prognosis assessment. The information included in this article is based on a critical analysis of selected published biomedical literature accessible through the United States National Library of Medicine's MEDLINE-PubMed and Scopus search engines. The majority of articles cited in this review and perspective, except for a few historical publications as background, were published between January 2000 and December 2013.     

Clinical impact of the troponin 99th percentile cut-off and clinical utility of myoglobin measurement in the early management of chest pain patients admitted to the Emergency Cardiology Department

OBJECTIVE: To verify the clinical impact of different low cut-offs for troponin I/cardiac troponin I (99th percentile to 10% CV) and for myoglobin, in early risk stratification of patients with suspected acute coronary syndrome. METHODS: A total of 516 consecutive non-ST-elevation patients admitted to hospital were followed. The first measurement of cardiac markers was performed at the point-of-care in the Emergency Cardiology Department, using Stratus CS. The lowest cardiac troponin I concentration with a CV0.07 microg/l in the Emergency Cardiology Department (P>0.05). Using lowering cut-off values, the difference between the fraction of patients that was positive compared with the diagnosis according to European Society of Cardiology and American College of Cardiology criteria and had remained statistically significant (P<0.05) up to 0.03 microg/l (99th percentile upper reference limit) was considered (85 patients, 16.5%, n.s.). Relative operating characteristic analysis confirmed that the best clinical cut-off was related to the cardiac troponin I concentration that meets the 99th percentile upper reference limit. The diagnostic accuracy of myoglobin in detecting the minimum cardiac damage was significantly lower, independently from the cut-offs considered. CONCLUSION: The diagnostic accuracy in detecting myocardial damage early in the Emergency Cardiology Department improves when the 99th percentile is used as a decisional value of cardiac troponin I; the use of this cut-off makes the measurement of myoglobin unnecessary.     

The Troponin Complex: Discriminating the Signal from the Noise

Patients presenting to the emergency department with consideration of an acute coronary syndrome (ACS) are risk-stratified with sensitive troponin assays. Among many patients who present with symptoms other than chest pain, they are admitted for observation if the troponin assay is above the upper reference limit of that specific assay. With the advent of high-sensitivity troponin assays, it is estimated that the prevalence of admissions for secondary myocardial infarctions, termed type 2 myocardial infarctions and myocardial injury, will increase by 100%. This is a heterogeneous population, and although adverse outcomes such as readmission and death are high, outcome-based therapies with guideline-directed treatments have not been advanced in this subset. As such, the clinician is often confused about the optimal treatment at hospital discharge. More studies should address the value of specific known therapies in this cohort that have been shown to improve outcomes in patients with an acute coronary syndrome or type 1 myocardial infarction.     

Abnormal troponin I levels in acute pulmonary embolism without abnormal concentrations of D-dimer at admission

Serum troponin I is a sensitive indicator of myocardial damage but abnormal troponin I levels have been reported without acute coronary syndrome and without cardiac damage. It has been reported that right ventricular overload and hypoxia in acute pulmonary embolism may lead to right ventricular myocardium injury reflected by elevated cardiac troponin levels and that in patients with acute central sub-massive or non-massive pulmonary embolism, even mild increase in troponin I >0.03 mug/L may provide relevant short-term prognostic information independent to clinical, laboratory and echocardiographic data. It has also been reported that patients with acute small pulmonary embolism might present with relatively low concentrations of D-dimer and it might have implications regarding the diagnostic yield of D-dimer in patients who are suspected of having an acute pulmonary embolism. We present a case of abnormal troponin I levels without abnormal concentrations of D-dimer at admission in a 26-year-old Italian man with acute pulmonary embolism. Also this case focuses attention on the importance of a correct evaluation of abnormal troponin I levels and not elevated D-dimer levels in acute pulmonary embolism.     

Efficacy of myocardial contrast echocardiography in the diagnosis and risk stratification of acute coronary syndrome

We examined the hypothesis that myocardial contrast echocardiography (MCE) is superior to conventional electrocardiographic, echocardiographic, and troponin I criteria for the diagnosis of acute coronary syndrome. We prospectively enrolled 114 consecutive patients (60+/-10 years of age, 73 men) who presented to the emergency room with chest pain on exertion and at rest. Exclusion criteria included an age<40 years, presence of Q wave or ST-segment elevation, and a poor echocardiographic window. Echocardiography and MCE were performed to assess regional wall motion abnormalities (RWMAs) and myocardial perfusion defects by using continuous infusion of perfluorocarbon-exposed sonicated dextrose albumin. Acute coronary syndrome was confirmed in 87 patients. There were no deaths; 46 patients had acute myocardial infarction, and 41 patients required urgent revascularization. On multiple logistic regression analysis, myocardial perfusion defect (odd ratio 87, p<0.001) was the only independent variable for diagnosing acute coronary syndrome. Myocardial perfusion defect (odd ratio 21, p=0.001) and troponin I levels (odd ratio 3, p=0.009) were independent predictors for acute myocardial infarction. The sensitivity of myocardial perfusion defect for diagnosing acute coronary syndrome was 77%, which is significantly higher than the sensitivities of ST change, troponin I increase, and RWMA (28%, 34%, and 49%, respectively), with similar specificities of 85% to 96%. In conclusion, MCE is more sensitive than the currently used electrocardiographic and troponin I criteria, and evaluation of myocardial perfusion defect by MCE complements RWMA analysis by conventional echocardiography for accurate diagnosis of acute coronary syndrome.