Prognostic utility of a next-generation high-sensitivity cardiac troponin T assay compared to an established high-sensitivity cardiac troponin I assay in the general population
J Lehmacher, A Haack, N A Soerensen, B Toprak, A Petersmann, S Blankenberg, J T Neumann, R TwerenboldAbstract
Background
Accurate cardiovascular risk prediction in the general population is crucial for early identification of high-risk individuals. High-sensitivity cardiac troponin (hs-cTn) has emerged as a promising circulating biomarker by indicating early, subclinical end-organ damage and thereby providing incremental prognostic utility beyond traditional risk factors. Until recently, this was largely limited to hs-cTnI, as the available hs-cTnT assay lacked sufficient low-end analytical sensitivity. A next-generation hs-cTnT assay with markedly improved analytical performance now enables reliable quantification of hs-cTnT in the general population.
Purpose
To compare the prognostic utility of a novel hs-cTnT with an established hs-cTnI assay in a population-based cohort.
Methods
We analyzed participants aged 45-79 years. Baseline hs-cTn concentrations were measured using the next-generation hs-cTnT assay (6th Generation) and an established hs-cTnI assay in blood samples collected at time of study inclusion. Co-primary outcomes were all-cause mortality (ACM) and major adverse cardiovascular events (MACE), including incident myocardial infarction, coronary revascularisation, stroke and ACM. Prognostic associations of log-transformed hs-cTnT and hs-cTnI values were evaluated using Cox proportional hazard models unadjusted, adjusted for age and sex and additionally adjusted for traditional cardiovascular risk factors. Discriminative performance of hs-cTnT and hs-cTnI was assessed using time-dependent ROC analysis.
Results
A total of 14,361 individuals (median age 60 years, 48.9% female) with available follow-up information were included. Hs-cTnT was detectable above the assay-specific limit of detection in 98.9% of individuals, compared with 81.6% for hs-cTnI. During a median follow-up time of 4.4 (IQR, 3.0-5.8) years, 322 deaths and 730 MACE occurred. Both, hs-cTnT and hs-cTnI were identified as strong and independent predictors of ACM and MACE, even after adjustment for age, sex and traditional risk factors (Table 1). Standardized effect estimates (hazard ratio per 1 standard deviation of log-transformed hs-cTn) were consistently higher for hs-cTnT than hs-cTnI. Time-dependent AUC demonstrated superior discrimination of hs-cTnT compared with hs-cTnI for ACM and MACE up to five years. (Figure 1). For ACM, AUCs at 1 year were 0.795 for hs-cTnT versus 0.719 for hs-cTnI (p=0.042), and at 5 years 0.742 versus 0.703 at 5 years (p=0.0037).
Conclusion
In the general population, both the next-generation hs-cTnT and the established hs-cTnI assays provide strong, independent prognostic information beyond traditional risk factors. In direct comparison, hs-cTnT seems to offer superior risk discrimination for mortality and cardiovascular events than hs-cTnI. Future risk-prediction models should incorporate circulating biomarkers such as hs-cTn to enhance predictive accuracy.