Impact of High-Sensitivity Troponin I Testing with Sex-Specific Cutoffs on the Diagnosis of Acute Myocardial Infarction

Abstract

BACKGROUND: High-sensitivity cardiac troponin I (hscTnI) assays show sex-dependent differences in the 99th percentile of healthy populations, with concentrations in women approximately 50% lower. The adoption of sex-specific cutoffs seems appropriate, although it is not yet clear what effect these will have on acute myocardial infarction (AMI) diagnosis and management. METHODS:We conducted a retrospective pre-and postchangeover analysis of troponin I testing in the 6 months before and after moving from the contemporary Abbott Architect TnI assay (cTnI) to hs-cTnI at 2 tertiary centers in Australia and New Zealand. The cTnI cutoff was 30 ng/L for both sexes, whereas a female-specific cutoff of 16 ng/L was adopted upon changeover to hsTnI. RESULTS:Changeover from the cTnI assay to the hs-cTnI assay increased the number of female patients with increased troponin I concentrations at both sites (from 29.7% to 34.9% and from 22.4% to 30.8%; P Ͻ 0.001). There was no statistically significant change in the number of men with increased concentrations in the same time period (P ϭ 0.09). The increased percentage of women with increased troponin I was not associated with an increase in the number of women with AMI diagnoses at either center. Angiographic data available from 1 center showed no change in the percentage of angiograms performed in women. CONCLUSIONS:Although increasing the proportion of women with increased troponin I, adopting sex-specific cutoffs with the hs-cTnI assay did not lead to an increase in AMI diagnoses in females, or in the number of women undergoing angiography. © 2016 American Association for Clinical ChemistryCardiac troponins are the preferred biomarkers for the detection of myocardial injury, and a rise and/or fall above the 99th percentile is an integral part of the universal consensus definition for diagnosis of acute myocardial infarction (AMI) 8 (1 ). In recent years, technical improvements have led to the development of highsensitivity assays that are capable of measuring low concentrations of cardiac troponin with high precision. With such assays, we are now able to measure cardiac troponin in the serum of healthy individuals, including children, who have no evidence of cardiovascular disease (2-4 ). The advent of high-sensitivity assays has uncovered sexspecific differences in circulating cardiac troponin concentrations that were formerly unrecognized because previous assays could not measure cardiac troponin with sufficient precision at or below the 99th percentile. It is now clear that the 99th percentile is substantially lower in females than it is in males (2,(5)(6)(7). Accordingly, several laboratories have implemented sex-specific reference intervals for cTnI, although the clinical impact is as yet unclear.The revelation of sex-dependent differences in circulating cardiac troponin raises several questions regarding the interpretation of cardiac troponin in women, and its possible downstream clinical effects. These are particularly pertinent given the large body of evidence suggest...

Rapid and safe discharge from the emergency department: A single troponin to exclude acute myocardial infarction

“…This assay has a limit of detection of 1.9 ng/L, and a coefficient of variation of 12.6% has been reported at 3.5 ng/L . We used the 99th sex specific percentile of ≥16 ng/L for women and ≥26 ng/L for men that reflects the agreed Australian reference intervals based on local and international reference data …”

“…12 We used the 99th sex specific percentile of ≥16 ng/L for women and ≥26 ng/L for men that reflects the agreed Australian reference intervals based on local and international reference data. 13,14 The primary exposure variable of interest was an initial very low troponin (HsTnI <5 ng/L) with a subsequent second troponin measurement that was abnormal (defined as ≥16 ng/L for women or ≥26 ng/L for men). Individual chart review of patients with the exposure variable involved assessment of presenting symptoms, initial ECG interpretation, cardiac risk factors, provocative cardiac stress tests, angiograms, PCI, CABG, and whether antiplatelet/anticoagulant medication was commenced at discharge.…”

Establishing consensus-based, assay-specific 99th percentile upper reference limits to facilitate proper utilization of cardiac troponin measurements

“…Clinical validation of the Abbott hs-cTn assay sex-specific decision limits was reported in a retrospective crossover study of two hospitals in Australia and New Zealand [43]. The audit included a number of statistics ranging from frequency of testing, rate of hs-cTnI elevation, rate of MI diagnosis and rate of angiography.…”

Point: The Use of Sex-Specific Cutpoints for High-Sensitivity Cardiac Troponin Assays

“…This study provides important insights about the clinical impact of sex-specific ranges (12 ). However, owing to absence of long-term outcome data, it remains unclear if changes in medical therapy occurred and if improved risk assessment had prognostic benefits for women.…”

“…The first report about the true clinical impact of the clinical use of sex-specific ranges in patient care has only recently been published (12 ). In accordance with guideline-recommendations (3)(4)(5), several laboratories have implemented sex-specific ranges for cardiac troponin I (cTnI).…”