Population differences and high-sensitivity troponin values: a narrative review

Abstract

Background and Objective: The 99th percentile upper reference limit (URL) of high-sensitivity troponin is used as a diagnostic threshold for acute myocardial infarction. It is not established if troponin differs across different populations. This narrative review discusses 99th percentile URLs of high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT) derived from healthy reference populations in different populations across different geographic locations. Methods: Articles investigating high-sensitivity troponin in healthy reference populations which reported sex-specific 99th percentile URLs, with a minimum of 800 subjects, and written in English were included. Besides more recent articles identified from PubMed and Google Scholar until December 2022, we included studies in the systematic review previously published by Kimenai in 2018 that met our inclusion criteria. Studies that did not use high-sensitivity troponin assays were excluded. Key Content and Findings: Nineteen articles (9 with hs-cTnT studies and 15 with hs-cTnI studies) were identified. The largest difference in hs-cTnT across studies was 19.6 ng/L, but very little difference was seen between similarly designed studies. The biggest difference in hs-cTnI (Abbott ARCHITECT STAT) was 22.9 ng/L. Expectedly, as hs-cTnI is not standardized differences exist between studies using different analytical platforms from different vendors. Reference cohort compositions and statistical treatment varied across all studies limiting comparison. Conclusions: Population differences in high-sensitivity troponin values do not appear to be very different across similarly studied populations for hs-cTnT in different countries. More differences are noted for hscTnI. Differences in 99th percentile hs-cTn URLs between populations are influenced by many variables including composition of the reference cohort and statistical methods employed. Male sex, increasing age, comorbidities such as subclinical heart disease, renal dysfunction and dysglycemia, and including outliers in analysis can raise hs-cTn 99th percentile URLs. Existing study designs investigating 99th percentile URLs of troponin have been heterogenous making it challenging to compare population differences in troponin concentrations. The jury is still out on whether troponin values differ across populations. Reference cohorts should include a representative distribution of the regional population composition in the applicable geographic area as recommended by expert committees.