Sex- and age-specific distribution of a next-generation high-sensitivity cardiac troponin T assay compared to established high-sensitivity cardiac troponin T and I assays in the general population

Background High-sensitivity cardiac troponin (hs-cTn) is a well-established diagnostic biomarker in the acute setting. Its use for prognostic purposes in the general population, however, is constrained by limited analytical sensitivity, particularly for hs-cTnT. A novel, 6th generation hs-cTnT assay with markedly enhanced sensitivity now enables reliable quantification of very low troponin concentrations, potentially supporting broader application in population-based settings. To define normal ranges and support clinical interpretation, robust data on age- and sex-specific hs-cTn distributions in the general population are essential but still lacking. Purpose To characterize the sex- and age-specific distribution of a novel hs-cTnT assay in the general population and compare it with established hs-cTnT and I assays. Methods We analyzed cross-sectional data from individuals aged 45-79 years enrolled in the population-based Hamburg City Health Study. Hs-cTn was retrospectively measured in baseline blood samples using a novel, 6th generation hs-cTnT assay, and established 5th generation hs-cTnT and 5th generation hs-cTnI assays. For all three assays, sex- and age-specific percentile distributions were calculated. In addition, age-specific reference percentile curves for the 6th generation hs-cTnT assay were generated separately for women and men. Uniform and sex-specific 99th percentiles were determined both in the unselected cohort and after applying the International Federation of Clinical Chemistry (IFCC)-recommended selection criteria, strictly excluding all individuals with any signs of cardiovascular risk factors or disease. Results In 15,351 individuals (median age 60 years, 48.9% female), 6th generation hs-cTnT assay detected concentrations above the limit of detection in 98.9% of individuals, compared with 75.8% (5th generation hs-cTnT) and 81.6% (5th generation hs-cTnI). Median 6th generation hs-cTnT concentration was 7 ng/L (IQR 4-11) in the overall population and significantly lower in women (median 5 ng/L, IQR 3-8) than in men (median 9 ng/L, IQR 6-14, p<0.001, Table 1). A J-shaped increase of hs-cTn with higher age was observed (Figure 1). The overall 99th percentile for the 6th generation hs-cTnT assay was 49 ng/L (34 ng/L in women, 58 ng/L in men). Only 26% of the population fulfilled the IFCC criteria, in which hs-cTnT levels were generally lower and the uniform 99th percentile was 28 ng/L (16 ng/L in women, 32 ng/L in men), closely matching the ones provided by the manufacturer (27 ng/L overall, 18 ng/L in women, 32 ng/L in men). Conclusion A novel hs-cTnT assay enabled quantification of hs-cTn in nearly 99% of the general population. Concentrations of hs-cTn vary strongly by sex and age. Sex- and age-specific reference percentile curves help to define “normal”, biologically expected values and may improve clinical interpretation of hs-cTn for diagnostic and prognostic use.