Analytical and assay issues for use of cardiac troponin testing for risk stratification in primary care

• Published in: Clinical biochemistry Vol. 46; no. 12; pp. 969 - 978
• Main Authors: Wu, Alan H.B., Christenson, Robert H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2013
• Subjects: Biological variation; Cardiac troponin; Chemistry Techniques, Analytical - methods; Humans; Immunoassay - methods; Myocardium - metabolism; Primary cardiovascular disease risk; Primary Health Care; Reversible injury; Risk Assessment; Standardization; Troponin - metabolism; II; ACC; RCV; ISO; CVA, CVI, CVG; ROC; Standardization; CK; SRM; Reversible injury; Biological variation; ESC; NACB; SI; Primary cardiovascular disease risk; AHA; Cardiac troponin; cTnI and cTnT; RM; AMI; SMCD; WHO; IFCC; International Organization for Standardization; CV(A), CV(I), CV(G); coefficient of variance analytical, intraindividual, and interindividual; National Academy of Clinical Biochemistry; standard reference material; creatine kinase; receiver operating characteristic; reference material; World Health Organization; cardiac troponin I and T; Standardization of Markers of Cardiac Damage; American College of Cardiology; International System of Units; index of individuality; American Heart Association; European Society of Cardiology; International Federation of Clinical Chemistry; reference change value; acute myocardial infarction
• ISSN: 0009-9120; 1873-2933; 1873-2933
• DOI: 10.1016/j.clinbiochem.2013.04.013

Cardiac troponin is the standard marker for diagnosis of acute myocardial infarction and risk stratification of patients who present to an emergency department with signs and symptoms of acute cardiac ischemia. Over the past few years, the analytical sensitivity of assays for cardiac troponin has improved significantly to the point where a detectable amount of troponin can be measured in essentially all healthy subjects. Recent studies have shown that use of a highly sensitive troponin assays may provide value to traditional markers of primary disease risk for patients, i.e., for those who have no history of heart disease. There are barriers to the adoption of cardiac troponin for screening high risk cohorts such as the elderly, diabetics and perhaps even the asymptomatic population. Strategies used for the assignment of cutoff concentrations in acute care, i.e., the 99th percentile, may not be appropriate for primary care as changes over baseline levels may provide more accurate information of risk than cross-sectional results. A review of biological variation has shown that cardiac troponin as a biomarker has low index of individuality, indicating that reference values are of little utility. Whether or not cardiac troponin can be released in reversible injury is a debate that could have significance for detecting minor myocardial injury. A major hurdle for use of troponin in primary care is the lack of assay standardization and nomenclature for the different generations of troponin assays. Standardization requires knowledge of what is released after cardiac injury and what the various cardiac troponin assays are measuring. Currently it is not clear if the cardiac troponin release after ischemic injury is identical to that in circulation of healthy individuals. This may affect the design of future assays and standardization approaches. There is potential that a marker of myocardial injury such as troponin can add to the value of existing indicators and biomarkers of cardiovascular disease risk. Additional analytical and clinical validations are needed to fully elucidate cardiac troponin metabolism and resolve ongoing clinical and laboratory issues. While these issues are directed to the use of troponin in primary care, most of these concepts are relevant to the use of troponin in acute coronary syndromes as well. •HS-troponin assays enable testing asymptomatic patients for heart disease.•Troponin release from the heart in healthy subjects has not been characterized.•Troponin has a low index of individuality thus reference values are not appropriate.•Standardization of troponin assays is essential in establishing baseline troponin.•Relabeling troponin assays and reporting units reduce confusion for its use.