Introduction and Hypothesis: Relations between elevated circulating cardiac troponin I (cTnI) levels and adverse cardiac outcomes were established prior to the advent of methods to measure extremely low levels of cTnI. Recently developed ELISA assays/platforms with ultra-high sensitivity cTnI (u-hs-cTnI) allow accurate measurement in healthy subjects. We hypothesized that women have lower u-hs-cTnI levels than their male counterparts, and that levels would also differ by age.
Methods: Two healthy cohorts (200 women, 200 men) aged 18-97 years were analyzed in duplicate using the Quanterix cTnI assay on the Simoa HD-1 Analyzer. The u-hs-cTnI 99th percentiles were calculated as the upper limits considering a robust estimation against outliers with 90% confidence intervals
Results and Discussion: The LLOD of u-hs-cTnI assay was calculated to be 0.005pg/ml; we accurately quantified u-hs-cTnI in 93% of healthy individuals. The combined 99th percentile was calculated to be 7.94 pg/ml (90% Confidence Interval [CI], 5.47-10.52). Women had lower mean u-hs-cTnI concentrations than men and only at older age approached male levels (Figure). The sex-specific 99th percentile for female vs. male individuals are 4.89 pg/ml (90%CI, 3.71-6.25) and 10.49 pg/ml (90%CI, 5.19-15.06), respectively.
Conclusion: U-hs-cTnI is detectable in 93% of healthy individuals using the Quanterix ELISA platform. Women under the age of 40 years have significantly lower levels of u-hs-cTnI than their healthy male counterparts. U-hs-cTnI increases with age and levels in women become comparable to men only after age of 40 years. These findings have implications for use of u-hs-cTnI for risk stratification purposes.
Figure: Comparing u-hs-cTnI Concentration in Female vs Male and Different Age Groups. The log (u-hs-cTnI Concentration) response: Age 0.025 ± 0.00398, p< 0.001, and Sex 1.019 ± 0.24589, p< 0.001.