Proposition of reference tables for a novel hs-cTnT assay to define “normal” considering relevant determinants in the general population

Background High-sensitivity cardiac troponin (hs-cTn) is a well-established diagnostic and prognostic biomarker in various clinical settings. Despite high myocardial specificity, concentrations of hs-cTn are influenced by a variety of factors like age, sex, prevalent cardiovascular disease and renal function, complicating physicians’ interpretation of hs-cTn concentrations. Recently, a novel next-generation hs-cTnT assay with substantially improved analytical sensitivity has been developed, potentially enabling its routine use for prognostic purposes in the general population. However, data on reference values of hs-cTnT concentrations in the general population and in clinically relevant subgroups are still scarce. Purpose We aimed to establish clinically practical reference values for a novel hs-cTnT assay, accounting for key determinants in the general population. Methods Cross-sectional data from participants of the population-based was used for analyses. Residents, aged 45 to 79 years were identified through the registration office and enrolled for comprehensive examinations and medical history assessment, including measurement of 6th generation hs-cTnT. Uni- and multivariable linear regression models were used to evaluate the associations of sex, age, estimated glomerular filtration rate (eGFR) and prevalent cardiovascular disease (CVD) with log-transformed hs-cTnT concentrations. Further, reference tables displaying median hs-cTnT concentrations were generated to propose expected reference values in clinically relevant subgroups of the general population. Results In 15,351 patients (median age 60 years, 48.9% female), we observed hs-cTnT concentrations being significantly associated with sex, age, eGFR and CVD in uni- and multivariable analyses (Table 1). Median concentrations observed in females varied by factor 8 and ranged from 3.1 ng/L in patients <60 years, with normal renal function and no prevalent CVD to 24.5 ng/L in patients ≥70 years, eGFR <45ml/min/m² and known CVD. In male patients, median hs-cTnT concentrations also varied by factor 8 and ranged between 6 ng/L and 48 ng/L in the respective population subgroups (Table 2). Conclusion Sex, age, CVD and eGFR are independent and clinically relevant determinants of 6th generation hs-cTnT concentrations in the general population, substantially influencing median values across subgroups. Reference tables that account for these factors may help physicians interpret hs-cTnT results by contrasting observed with biologically expected hs-cTnT concentrations. This approach has the potential to enhance diagnostic and prognostic decision making, particularly in heterogeneous or diseased populations.