Determination of high‐sensitivity cardiac troponin T upper reference limits under the improved selection criteria in a Chinese population

Abstract

Background:There is no common consensus on how to define the reference population for determination of high-sensitivity cardiac troponin (hs-cTn) upper reference limit (URL). This study aimed to establish 99th percentile URLs of hs-cTnT under both 2018 AACC/IFCC criteria and improved selection criteria for further judging whether two URLs are different. Methods:Applying the stratified cluster sampling protocol, this study took 1848 apparently healthy subjects in communities of Shenyang China as the screening objects.We first followed 2018 AACC/IFCC criteria using surrogate biomarker for diabetes, myocardial dysfunction, renal dysfunction, and electrocardiogram. Then, we followed improved selection criteria to exclude hypertension, overweight and obesity, and dyslipidemia by physical examination and laboratory screening. Accordingly, 99th percentile URLs of hs-cTnT were established. Results: If the 2018 AACC/IFCC criteria were applied, 99th percentile URLs (90% confidence interval) of hs-cTnT male, female, and total were 19 (17-20) ng/L, 16 (15-17) ng/L, and 18 (16-19) ng/L, respectively. If added a single supplementary selection criteria, 99th percentile URLs of hs-cTnT total reduced to 16 ng/L, 17 ng/L, and 16 ng/L, respectively. If the improved selection criteria were applied, 99th percentile URLs (90% confidence interval) of hs-cTnT male, female, and total were 18 (14-24) ng/L, 13 (11-16) ng/L, and 16 (13-17) ng/L, respectively. The 99th percentile URLs of hs-cTnT male were higher than those of female in every age group. Conclusions: Improved selection criteria through questionnaire survey, physical examination, and laboratory screening to further exclude hypertension, overweight and obesity, and dyslipidemia can avoid overestimation of the 99th percentile URL of hs-cTnT. K E Y W O R D S 99th percentile, high-sensitivity cardiac troponin T, reference population, selection criteria This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Clinical relevance of biological variation of cardiac troponins

“…Indeed, the 10% of cTnI values, measured with high-sensitivity methods in a large Italian population, are actually lower than 2 ng/L [19]. Considering the cTnT assay, about 20-25% of apparently healthy adult European and Chinese men and women [20][21][22] showed cTnT values ≤3 ng/L (i.e., the LoD of the method).…”

“…From a pathophysiological perspective, several authors have suggested that the circulating levels of hs-cTn measured in healthy adult subjects should be considered a reliable index of the physiological cardiomyocyte renewal [14][15][16][17][18][19][23][24][25], which is defined as the ability to replace loss of cardiomyocytes by new ones [26]. In particular, some recent clinical studies report that the 99th percentile URL values of hs-cTn methods are on average ranging from 13 to 47 ng/L [13,[17][18][19][20][21][22], corresponding to about 30-40 mg of cardiomyocyte renewal [17,23,24]. Accordingly, the mean hs-cTn concentrations of about 3-5 ng/L, typical of adult healthy subjects, are related to a myocardial volume ≤10 mg.…”

Influence of Age on the Diagnosis of Myocardial Infarction

“…Approaches to sequentially exclude patients from reference populations used to derive the 99th centile using such testing has been shown to affect the threshold level, in particular, in older patients. 8,38,39 Of note, the addition of comorbidities to our baseline model resulted in an improvement in model discrimination, suggesting that approaches which consider multiple individual patient factors could offer an alternative to threshold-based diagnosis. 40 One such example is the myocardial infarction 3 model that uses machine learning to provide individual probability estimates and has been shown to perform favorably in an observational study with superior specificity and PPV compared with universal thresholds.…”

“…Approaches to sequentially exclude patients from reference populations used to derive the 99th centile using such testing has been shown to affect the threshold level, in particular, in older patients. 8 , 38 , 39 …”

Determination of Age- and Sex-Specific 99th Percentile Upper Reference Limits for High-Sensitivity Cardiac Troponin I in Healthy Chinese Adults

“…Subjects who reported no cardiovascular disease or medication use performed an electrocardiogram (ECG), a physical examination, and laboratory testing. Exclusion criteria included pregnancy, a recent blood transfusion or blood donation, hypertension, individuals under 20 years old, HbA1c >6.5% (alternative biomarker of diabetes), eGFR ≤60 mL/min/1.73 m 2 (alternative biomarker of renal dysfunction), N-terminal-pro-B-type natriuretic peptide (NT-proBNP) >125 pg/mL (<75 years) or 450 pg/mL (≥75 years) (alternative biomarker of myocardial dysfunction), overweight or obesity (body mass index ≥25.0 kg/m 2 ), and the history of dyslipidemia or TG >2.3 mmol/L, total cholesterol >6.2 mmol/L, low-density lipoprotein >4.1 mmol/L, and high-density lipoprotein ≤1.0 mmol/L [ 11 ]. According to the principles of Helsinki declaration, this study was approved by the Ethics Committee of the First Hospital of Jilin University.…”