Dorien M Kimenai1, Ronald M A Henry2, Carla J H van der Kallen2, Pieter C Dagnelie3, Miranda T Schram2, Coen D A Stehouwer4, Jeroen D E van Suijlen5, Marijke Niens5, Otto Bekers1, Simone J S Sep2, Nicolaas C Schaper4, Marja P van Dieijen-Visser1, Steven J R Meex1. 1. Department of Clinical Chemistry, Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands. 2. Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands Department of Medicine, MUMC, Maastricht, The Netherlands. 3. Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands Department of Epidemiology, MUMC, Maastricht, The Netherlands School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands. 4. Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands Department of Medicine, MUMC, Maastricht, The Netherlands School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands. 5. Department of Clinical Chemistry, Gelre Hospital, Apeldoorn, The Netherlands.
Abstract
OBJECTIVE: The 99th percentile upper reference limit of high-sensitivity cardiac troponin (hs-cTn) from a healthy reference population is used for diagnosing acute myocardial infarction (AMI). Accepted current thresholds of hs-cTnT (Roche) and hs-cTnI (Abbott) are 14 and 26 ng/L, respectively. Since thresholds for hs-cTnT and hs-cTnI were derived from different reference cohorts it is unclear whether they are biologically equivalent. We directly assessed sex-specific and age-specific 99th percentile upper reference limits of hs-cTnT and hs-cTnI in a single reference cohort, to investigate whether current divergent thresholds of hs-cTnT and hs-cTnI stem from intrinsic assay differences or reflect cohort variation. METHODS: A healthy reference population was derived from a population-based cohort (the Maastricht Study: n=3451; age: 40-75 years). Individuals with diabetes mellitus, a history of cardiovascular disease, cardiac ischaemia on ECG, N-terminal pro-brain natriuretic peptide >125 ng/L or estimated glomerular filtration rate <60 mL/min/1.73 m(2) were excluded. Non-parametric analyses were performed to assess 99th percentile upper reference limits. RESULTS: 1540 individuals were included in the healthy reference population (age 57±8 years, 52.4% women). Overall 99th percentile upper reference limits of hs-cTnT and hs-cTnI were 15 and 13 ng/L, respectively. Upper reference limits were higher in men than women (hs-cTnT: 16 vs 12 ng/L), (hs-cTnI: 20 vs 11 ng/L) and increased with age. CONCLUSIONS: Direct comparison reveals numerically similar thresholds for hs-cTnT and hs-cTnI assays. This finding is in line with recently reported underdiagnosis of AMI with the current decision limit of 26 ng/L for hs-cTnI, especially among women. Downwards adjustment of the hs-cTnI threshold, differentiated for sex, would equalise clinical decision limits for both assays, and may prevent further underdiagnosis of AMI. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
OBJECTIVE: The 99th percentile upper reference limit of high-sensitivity cardiac troponin (hs-cTn) from a healthy reference population is used for diagnosing acute myocardial infarction (AMI). Accepted current thresholds of hs-cTnT (Roche) and hs-cTnI (Abbott) are 14 and 26 ng/L, respectively. Since thresholds for hs-cTnT and hs-cTnI were derived from different reference cohorts it is unclear whether they are biologically equivalent. We directly assessed sex-specific and age-specific 99th percentile upper reference limits of hs-cTnT and hs-cTnI in a single reference cohort, to investigate whether current divergent thresholds of hs-cTnT and hs-cTnI stem from intrinsic assay differences or reflect cohort variation. METHODS: A healthy reference population was derived from a population-based cohort (the Maastricht Study: n=3451; age: 40-75 years). Individuals with diabetes mellitus, a history of cardiovascular disease, cardiac ischaemia on ECG, N-terminal pro-brain natriuretic peptide >125 ng/L or estimated glomerular filtration rate <60 mL/min/1.73 m(2) were excluded. Non-parametric analyses were performed to assess 99th percentile upper reference limits. RESULTS: 1540 individuals were included in the healthy reference population (age 57±8 years, 52.4% women). Overall 99th percentile upper reference limits of hs-cTnT and hs-cTnI were 15 and 13 ng/L, respectively. Upper reference limits were higher in men than women (hs-cTnT: 16 vs 12 ng/L), (hs-cTnI: 20 vs 11 ng/L) and increased with age. CONCLUSIONS: Direct comparison reveals numerically similar thresholds for hs-cTnT and hs-cTnI assays. This finding is in line with recently reported underdiagnosis of AMI with the current decision limit of 26 ng/L for hs-cTnI, especially among women. Downwards adjustment of the hs-cTnI threshold, differentiated for sex, would equalise clinical decision limits for both assays, and may prevent further underdiagnosis of AMI. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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