Background
Highly sensitive cardiac troponin T (hs-cTnT) plays an essential role in the diagnosis of myocardial injury. The upper reference limit of the respective assay (e.g. 14 ng/l for the Elecsys® assay) is generally applied, irrespective of age, sex, or kidney function. We aimed to identify age- and sex-adjusted upper reference limits in relation to renal function in a large population-based cohort without cardiovascular diseases.  

Methods
We included 5,428 subjects of the population-based LIFE-Adult cohort, free of cardiac diseases. Sex-related significant differences of hs-cTnT levels were analyzed in different age groups. We used Spearman’s rank correlation for correlation analyses of hs-cTnT serum concentrations and age or creatinine. Sex- and age-adjusted 99th percentiles for hs-cTnT in subjects with preserved renal function (eGFR ≥ 60/ml/min/1.73 m²) were obtained using NumPy’s percentile function.

Results
The hs-cTnT values were higher in men of all age groups (Figure 1). In both sexes, increasing age positively correlated with higher hs-cTnT values (ρ = 0.42 p < 0.001, Figure 1). Hs-cTnT weakly correlated with serum creatinine (ρ = 0.16 / 0.18 in women / men, p < 0.001 in both), which we found to be an age-related effect. The three-dimensional analysis of age, creatinine, and hs-cTnT showed no relevant additional effect of creatinine values of up to 150 µmol/l on hs-cTnT levels. We obtained age- and sex-adjusted upper reference limits (defined as 99th percentiles). In men aged above 60 and women above 70, the calculated 99th percentiles clearly exceeded the commonly applied threshold of 14 ng/l (Figure 1).

Conclusion
Age and sex have a major impact on the serum concentration of hs-cTnT, while kidney function does not. We propose to consider age- and sex-adjusted upper reference limits in the elderly.



Figure 1: Age-specific floating median (circles) and 99th percentile (squares) hs-cTnT values in females (red) and males (blue) with preserved kidney function. The ranges of 97th–99.4th hs-cTnT percentiles (smoothed with a window size of +/- 10 years per point) are highlighted in light red (females) and light blue (males). Hs-cTnT: highly sensitive troponin T.