1.
Utility of traditional circulating and imaging-based cardiac biomarkers in patients with predialysis CKD.
Colbert, G, Jain, N, de Lemos, JA, Hedayati, SS
Clinical journal of the American Society of Nephrology : CJASN. 2015;(3):515-29
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Abstract
Cardiac biomarkers, such as cardiac troponin T (cTnT), brain natriuretic peptide (BNP), and N-terminal-pro-BNP (NT-pro-BNP), are commonly used to diagnose acute coronary syndrome and congestive heart failure exacerbation in symptomatic patients. Levels of these biomarkers are frequently chronically elevated in asymptomatic patients with ESRD who are receiving maintenance dialysis. Other imaging biomarkers commonly encountered in nephrologists' clinical practice, such as coronary artery calcium measured by computed tomography, left ventricular hypertrophy, and carotid intima-media thickness, are also frequently abnormal in asymptomatic patients with ESRD. This article critically reviews the limited observational data on associations between cTnT, BNP, NT-pro-BNP, coronary artery calcium, left ventricular hypertrophy, and carotid intima-media thickness with cardiovascular events and death in non-dialysis-dependent patients with CKD. Although sufficient evidence suggests that these biomarkers may be used for prognostication, the diagnostic utility of cTnT, BNP, and NT-pro-BNP remain challenging in patients with CKD. Decreased renal clearance may affect the plasma levels of these biomarkers, and upper reference limits were originally derived in patients without CKD. Until better data are available, higher cutoffs, or a rise in level compared with previous values, have been proposed to help distinguish acute myocardial infarction from chronic elevations of cTnT in symptomatic patients with CKD. Additionally, it is not known whether these biomarkers are modifiable and amenable to interventions that could change hard clinical outcomes in patients with CKD not yet undergoing long-term dialysis.
2.
Current trends in diagnostic biomarkers of acute coronary syndrome.
Moe, KT, Wong, P
Annals of the Academy of Medicine, Singapore. 2010;(3):210-5
Abstract
The diagnosis and management of patients with acute coronary syndrome (ACS) have evolved dramatically over the past decade. Biomarkers play an important role in the diagnosis of ACS, especially in unstable angina and non-ST-segment elevation myocardial infarction. Among these, cardiac troponin and creatine kinase appear to be the most sensitive and specific markers of myocardial injury. Recent studies have revealed several novel biomarkers. Elevated levels of C-reactive protein and interleukin-6 are strong independent markers of increased mortality among patients with ACS. However, the ideal biomarkers that offer early detection, risk stratification, selection of therapy, monitoring disease progression, and treatment efficacy remain to be elucidated. This review assesses limitations and contemporary needs for biomarkers in the context of diagnosis of ACS. It also discusses the newly developing technologies for novel biomarkers or novel biomarker protein signatures discovery, and importance of point-of-care testing for future management.
3.
Myocardial regulatory proteins and heart failure.
Adamcová, M, Stĕrba, M, Simůnek, T, Potácová, A, Popelová, O, Gersl, V
European journal of heart failure. 2006;(4):333-42
Abstract
Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) are considered to be the most specific and sensitive biochemical markers of myocardial damage. Troponins have been studied in a wide range of clinical settings, including heart failure; however, there are few data on the role of regulatory proteins in the pathogenesis of heart failure, although a few interesting hypotheses have been proposed. A considerable body of evidence favours the view that alteration of the myocardial thin filament is the primary event leading to defective contractility of the failing myocardium, while the changes in Ca(2+) handling are a compensatory response. A better understanding of the role of regulatory proteins under different physiological and pathological conditions could lead to new therapeutic approaches in heart failure. Recently, calcium sensitisation has been proposed as a novel method by which cardiac performance may be enhanced via an increase in the affinity of troponin C for calcium but without affecting intracellular calcium concentration. To date, the only calcium sensitizer used in clinical practice is levosimendan.
4.
Cardiac troponins in renal insufficiency: review and clinical implications.
Freda, BJ, Tang, WH, Van Lente, F, Peacock, WF, Francis, GS
Journal of the American College of Cardiology. 2002;(12):2065-71
Abstract
Patients with renal insufficiency may have increased serum troponins even in the absence of clinically suspected acute myocardial ischemia. While cardiovascular disease is the most common cause of death in patients with renal failure, we are just beginning to understand the clinical meaning of serum troponin elevations. Serum troponin T is increased more frequently than troponin I in patients with renal failure, leading clinicians to question its specificity for the diagnosis of myocardial infarction. Many large-scale trials demonstrating the utility of serum troponins in predicting adverse events and in guiding therapy and intervention in acute coronary syndromes have excluded patients with renal failure. Despite persistent uncertainty about the mechanism of elevated serum troponins in patients with reduced renal function, data from smaller groups of renal failure patients have suggested that troponin elevations are associated with added risk, including an increase in mortality. It is possible that increases in serum troponin from baseline in patients with renal insufficiency admitted to hospital with acute coronary syndrome may signify myocardial necrosis. Further studies are needed to clarify this hypothesis.
5.
Ingenuous interpretation of elevated blood levels of macromolecular markers of myocardial injury: a recipe for confusion.
Sobel, BE, LeWinter, MM
Journal of the American College of Cardiology. 2000;(5):1355-8
Abstract
Several assumptions about elevations of macromolecular markers of myocardial injury in blood require critical consideration. The dichotomy of modest, persistent elevations of troponins I and T as prognostic factors in patients with unstable angina and absent elevations of isoenzymes of creatine kinase is presently unexplained. Factors influencing the appearance of macromolecular markers of myocardial injury in blood are considered, including the need to estimate baseline values, to consider elevations as deviations from baseline rather than simply points within a distribution of baseline values in normal subjects, to recognize operative biochemical and physiologic determinants of marker release from injured myocytes and washout and to take into account the influence of apoptosis. Elucidation and consideration of mechanisms underlying the appearance of specific macromolecular markers in blood appear likely to improve diagnosis and explain the prognostic power of the troponins in patients with unstable angina. Detection of proteolytic breakdown products of troponins in blood is likely to explain the modest, persistent elevations seen in some patients with unstable angina and their prognostic implications.