Prognostic value of changes in high-sensitivity cardiac troponin T beyond biological variation in stable outpatients with cardiovascular disease: a validation study

Abstract

Objective: To evaluate the prognostic implications of longitudinal long-term changes beyond the biological variation of high-sensitivity cardiac troponin T (hs-cTnT) in outpatients with stable or asymptomatic cardiovascular disease (CV) and to assess possible differences in the prognostic value while using reference change value (RCV) and minimal important differences (MID) as metric for biological variation.

Methods: Hs-cTnT was measured at index visit and after 12 months in outpatients presenting for routine follow-up. The prognostic relevance of a concentration change of hs-cTnT values exceeding the biological variation defined by RCV and MID of a healthy population within the next 12 months following the stable initial period was determined regarding three endpoints: all-cause mortality (EP1), a composite of all-cause mortality, non-fatal myocardial infarction and stroke (EP2), and a composite of all-cause mortality, non-fatal myocardial infarction, stroke, hospitalization for acute coronary syndrome (ACS) or decompensated heart failure, and planned and unplanned percutaneous coronary interventions (PCI, EP3).

Results: Change in hs-cTnT values exceeding the biovariability defined by MID but not by RCV discriminated a group with a higher cardiovascular risk profile. Changes within MID were associated with uneventful course (NPV 91.6-99.7%) while changes exceeding MID were associated with a higher occurrence of all endpoints within the next 365 days indicating a 5.5-fold increased risk for EP 1 (p = 0.041) a 2.4-fold increased risk for EP 2 (p = 0.049) and a 1.9-fold increased risk for EP 3 (p < 0.0001).

Conclusions: In stable outpatients MID calculated from hs-cTnT changes measured 365 ± 120 days apart are helpful to predict an uneventful clinical course.

Clinical trials identifier: NCT01954303.

Keywords: Biological variation; Cardiovascular disease; High-sensitivity Troponin T; Outcomes; Outpatients.

Conflict of interest statement

M.B. reports grants and non-financial support from AstraZeneca, non-financial support from Brahms Thermo Fisher, outside the submitted work; E.G. reports grants, personal fees and non-financial support from Roche Diagnostics, grants, personal fees and non-financial support from AstraZeneca, grants, personal fees and non-financial support from Bayer Vital, grants, personal fees and non-financial support from Brahms Thermo Fisher, personal fees from Daiichi Sankyo, personal fees from Boehringer Ingelheim, outside the submitted work. M.M.-H., reports research support by the Medical Faculty of Heidelberg University, research support from Roche Diagnostics and BRAHMS Thermo Scientific, speaker honoraria from Roche Diagnostics, non-financial support by BRAHMS Thermo Scientific, Bayer Vital GmbH, Daiichi-Sankyo, Metanomics Health GmbH and Philips Electronics, outside the submitted work. All the other authors have nothing to disclose. HAK received honoraria for lecturers from Roche Diagnostics, AstraZeneca, Bayer Vital, Daiichi-Sankyo, and held a patent on cTnT that has expired. All the other authors have no conflicts of interest to declare.

© 2021. The Author(s).

Figures

Fig. 1

Study population

Fig. 2

Hazard ratios for the endpoint. All-cause mortality depending on hs-cTnT ≤ 14 ng/l on first visit, hs-cTnT  14 ng/l at first visit

Fig. 3

Kaplan–Meier survival curves for all-cause mortality depending on MID and RCV values within or out of reference