Ultra-highly sensitive cardiac troponin I: Age and sex differences in healthy individuals

Associations between elevated circulating cardiac troponin I (cTnI) levels and adverse cardiac outcomes were established prior to the ability to measure extremely low levels of cTnI. Immunoassays that achieve precise ultra-highly sensitive quantification of cTnI (u-hs-cTnI) will allow accurate measurement in healthy subjects. We aimed to evaluate the distribution of u-hs-cTnI values measured by (Simoa HD-1 Analyzer, Quanterix Corporation, Lexington, MA) in healthy subjects and characterize relations to sex and age.

Two independent, healthy cohorts (total of 200 women, 200 men) aged 18-86 years were analyzed in duplicate using the u-hs-cTnI Immunoassay. The u-hs-cTnI 99th percentiles were calculated as the upper limits considering a robust estimation against outliers with 90% confidence intervals. The Quanterix immunoassay analytical performance was established and compared to an existing clinical assay (ARCHITECT STAT High Sensitivity Troponin I, Abbott Laboratories, Wiesbaden, Germany).

The lower limit of detection of the u-hs-cTnI assay was calculated to be 0.005 ng/L; we accurately quantified u-hs-cTnI in 95% of healthy individuals. The Quanterix immunoassay within overlapping concentrations correlated with the Abbott assay (R2 = 0.932). The calculated combined 99th percentile was 7.94 ng/L (90% Confidence Interval [CI], 5.47-10.52). Women had lower mean u-hs-cTnI concentrations than men under the age of 40 years. The sex-specific 99th percentile for female vs. male individuals was 4.89 ng/L (90%CI, 3.71-6.25) and 10.49 ng/L (90%CI, 5.19-15.06), respectively.

The Quanterix immunoassay provides precise quantification in 95% of healthy individuals. Women under the age of 40 years have significantly lower levels of u-hs-cTnI than men.