Creation of a Universal Sample Bank for Determining the 99th Percentile for Cardiac Troponin Assays

Abstract

Background: International guidelines authored and endorsed by professional societies of cardiology, emergency medicine, and laboratory medicine are unanimous that the cutoff concentration for establishing a diagnosis of acute myocardial infarction be set at the 99th percentile of a healthy population. The establishment of the actual 99th percentile value is assay- and sample-dependent and is influenced by the population of individuals selected for testing. We created a sample bank that will enable manufacturers of troponin assays a consistent comparison of the 99th percentile. Methods: Participants were recruited from those attending the 2015 Annual Meeting of the AACC for the creation of a universal sample bank of apparently healthy individuals (free from uncontrolled diabetes, renal insufficiency, and heart disease). For those who met eligibility criteria and signed a written consent to participate, 60 mL blood was collected into 6 10-mL tubes each (2 serum, 3 heparin plasma, and 1 EDTA). Whole blood was tested for hemoglobin (Hb) A1c, and serum was tested for N-terminal pro–B-type natriuretic peptide (NT-proBNP) and creatinine. Results: There were a total of 764 individuals who consented during the AACC Annual Meeting. After this initial enrollment, it was determined that there was an insufficient number of male participants recruited. Under the same protocol and consent, blood from 131 additional males was collected at the University of Maryland. Samples were centrifuged, and 240 μL aliquots of the 2 serum, 3 heparin plasma, and 1 EDTA tubes were frozen at 70 °C within 2 h of collection. The labeled samples were divided into boxes containing 1 aliquot from each individual. Sets of these samples were made available for purchase to manufacturers of cardiac troponin assays. Eighty-eight samples were excluded from the database for having a high NT-proBNP (>300 ng/L), low estimated glomerular filtration rate (eGFR) (<60 mL/min/1.73 m2), high Hb A1c (≥6.5%), or preanalytical sample issues and consenting/ data issues. The final total was 808 individuals (402 females and 406 males; 60% Caucasian, 26% African or African American, 11% Asian or Pacific Islander, and 3% other). Conclusions: The creation of a bank of samples from healthy individuals enables a consistent comparison of the 99th percentile results from manufacturers of cardiac troponin assays.