High-sensitivity cardiac troponin testing for primary care: analytical assay considerations required before widespread implementation

For over 20 years, cardiac troponins T and I have been used as a biomarker for diagnosis of acute coronary syndromes (ACS) and risk stratification for future adverse cardiac events (1,2). Results of cardiac troponin testing produces higher clinical sensitivity and specificity than testing for the creatine kinase-MB (CK-MB) isoenzyme, and today, is recognized as the preferred marker for use in patients suspected of acute myocardial infarction (3). As with other clinical lab tests, the ones for cardiac troponin have undergone improvements over the years, especially with regards to analytical sensitivity and precision. This is reflected by the fact that using the first generation assay, it was not possible to reliably detect cardiac troponin in healthy subjects. As such, the cutoff was established at a troponin concentration that produced an acceptable assay precision, e.g., 10%, rather than the traditional approach of testing a reference population. With release of next generation assays, the 99th percentile upper limit of normal was used as the cutoff, as recommended by international cardiology guidelines. With each improvement in troponin assays, this cutoff for detecting myocardial injury has progressively been lowered. Today, with the commercial release of “high-sensitivity” (HS) assays, cardiac troponin can be detected in all subjects with precision below 10% (4), and the 99th percentile limit is typically between 10 and 20 ng/L. Use of HS troponins has enabled physicians to detect more patients who have myocardial injury, including those without ACS