Plasma 99th percentile reference limits for cardiac troponin and creatine kinase MB mass for use with European Society of Cardiology American College of Cardiology consensus recommendations

Background: The European Society of Cardiology/ American College of Cardiology (ESC/ACC) consensus document for definition of myocardial infarction (MI) is predicated on increased cardiac troponin or creatine kinase (CK) MB mass above the 99th percentile reference limit. The purpose of this study was to determine the plasma (heparin) 99th percentile reference limits for the leading in vitro diagnostic cardiac troponin and CKMB mass assays. Methods: Blood (heparin plasma) was obtained from healthy adults (n = 696; age range, 18-84 years) stratified by gender and ethnicity. Cardiac troponin I (cTnI) and T (cTnT) and CKMB mass concentrations were measured by eight assays. Reference limits were determined by nonparametric statistical Analysis. Results: Two cTnI assays demonstrated at least a 1.2- to 2.5-fold higher 99th. percentile for males vs females, with the mean concentrations significantly higher for males (P < 0.05). Two cTnI assays also demonstrated a 1.1- to 2.8-fold higher 99th percentile for blacks vs Caucasians, with the mean concentrations significantly higher for blacks (P = 0.05). There Was a 13-fold variance between the lowest measured 99th percentile (0.06 mug/L) and the highest (0.8 mug/L). All CKMB assays demonstrated a 1.2 to 2.6-fold higher 99th percentile for males vs females, with mean concentrations significantly higher for males (P <0.0001). Four CKMB assays also showed significantly higher (1.2- to 2.7-fold) mean concentrations for blacks (P <0.02) vs Caucasians. Conclusions: The heparin-plasma 99th percentile reference limits for cardiac troponin and CKMB mass provide an evidence base in support of the ESC, ACC, and American Heart Association guidelines for detection of myocardial injury. Selective gender and ethnic differences were demonstrated. These data allow clinicians, trialists, and epidemiologists a common point for operational use. (C) 2003 American Association for Clinical Chemistry.