Introduction
The 99th percentile upper reference limit (URL) of cardiac troponin (cTn) is diagnostic cutoff for myocardial infarction (MI). Several factors are known to lead to an increase in cTn including sex, kidney function, left ventricular function and various comorbidities. Similarly, studies have shown that cTn concentration of patients increase with age. However, the impact of age on the concentration of cTn in healthy individuals is unclear as several studies of healthy populations showed little to no impact of age.

Purpose
To determine the effect of age on the URL of cTn for the Danish population.

Methods
We invited active and retired blood donors with the aim of including 250 participants of each sex in each of four age groups, <50, 50–60, 60–70 and >70 years, for a total of about 2000 participants. cTn levels were measured by 4 cTn assays (Siemens Atellica and Vista cTnI, Roche cTnT and Abbott Alinity cTnI). The age specific URL were calculated using the non-parametric method. Quantile regression for the 99th percentile was adjusted for sex and creatinine concentration.

Results
A total of 2287 participants were sampled in the study, of which 4 (0.2%) were excluded due to a history of heart disease and 7 (0.3%) were excluded due to insufficient plasma for screening biomarkers. The median age was 58.6 (IQR 48.2–69.7), and 52.6% were female. Figure 1 shows the distribution of cTn concentrations in age intervals. There was a significant increase in cTn with age for all assays (all p<0.001). After adjusting for sex and creatinine concentration, increasing age was only significantly associated with cTnT (0.40 ng/L increase per year, p=0.03). Figure 2 panel A shows the age specific URL for each assay, where we observed a significant difference for cTnT with the URL increasing from 15.8 ng/L (90% CI 12.4–33.9 ng/L) for participants <50 years to 37.6 ng/L (90% CI 34.6–41.5 ng/L) for participants >70 years. The proportion of participants with concentrations above the manufacturers URL increased with age for cTnT from 1.5% in participants <50 years to 25.6% for participants >70 years (p<0.001), figure 2 panel B. This changed little when removing participants with decreased kidney function (eGFR <60 mL/min/1.73 m2) as 24.3% of the remaining participants >70 years had a cTnT above the URL.

Conclusions
The concentration of cTn increased with age for all assays. This was clearest for cTnT in which the 99th percentiles of participants were significantly different for participants age >70 years of whom a quarter had cTnT levels above the level for myocardial injury according to the manufacturer's URL.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): HelsefondenMauritzen La Fountaine Foundation