Stable high-sensitivity cardiac troponin T levels and outcomes

Background: Many patients who seek medical attention because of chest pain in the emergency department (ED), without myocardial infarction (MI) as a final diagnosis, will have cardiac troponin (cTn) levels above the upper normal limit when measured with the high-sensitivity cardiac troponin T (hs-cTnT) assay. In patients with acute medical diseases other than MI which may affect hs-cTn levels, treatment strategies focus on underlying conditions. However, stable elevation of hs-cTnT levels not related to any acute medical condition indicates chronic myocardial injury, which is a rather newly recognized entity. Knowledge about the prognosis in chronic myocardial injury is limited. The aim of this thesis was to investigate the implications of detectable and elevated hs-cTnT levels in patients without MI.

Methods: The study population were patients with chest pain in the ED at Karolinska University Hospital from 2011 to 2014. The cohorts were identified in the local administrative database of all patients seeking medical attention in the ED, while additional data were retrieved from national patient registers. Study I was performed to investigate long-term outcomes in patients with stable hs-cTnT levels but no MI (n=19,460). Study II was performed to investigate how patients with chest pain and elevated hs-cTnT levels but no MI (n=1848) are investigated, treated, and followed-up, compared with patients with MI (n=927). Study III was performed to compare long-term prognosis in patients with stable hs-cTnT levels in study I (n=19,460) with patients with Non-ST-Segment Elevation Myocardial Infarction (NSTEMI) from the same original cohort of patients with chest pain in the ED (n=1269). Study IV was performed to investigate diurnal variation in admission hs-cTnT levels in patients with stable hs-cTnT levels in study I (n=19,460), i.e. if the time of the day needs to be considered when assessing hs-cTnT levels.

Results: In patients with stable hs-cTnT levels, a graded association was found between the hs-cTnT level and risk of death, MI and heart failure. Findings were consistent across all sub groups, e.g. in patients with and without established heart disease and chronic kidney disease. Only minimal diurnal variation in admission hs-cTnT levels, which disappeared after age-adjustment, was observed in these patients. Patients with chronic myocardial injury and hs-cTnT levels 10-29 g/l were found to have a similar long-term risk of death as patients with NSTEMI, while the risk was higher at hs-cTnT levels >30 ng/l. Patients with elevated hs-cTnT levels but no MI were found to infrequently undergo cardiac investigations, were rarely prescribed new cardiovascular medications, and were less likely to have a planned follow-up after discharge compared to patients with MI.

Conclusions: Patients with stable hs-cTnT levels have a high risk of premature death and cardiovascular disease, yet infrequently undergo cardiac investigations. This should merit further attention, as today there are no clinical guidelines for clinical management of these patients.

List of scientific papers

I. Stable high-sensitivity cardiac troponin t levels and outcomes in patients with chest pain. Andreas Roos, Nadia Bandstein, Magnus Lundbäck, Ola Hammarsten, Rickard Ljung, Martin J. Holzmann. Journal of the American College of Cardiology. 2017;70:2226-2236.
https://doi.org/10.1016/j.jacc.2017.08.064

II. Investigations, findings, and follow-up in patients with chest pain and elevated high-sensitivity cardiac troponin T levels but no myocardial infarction. Andreas Roos, Anton Hellgren, Farshid Rafatnia, Ola Hammarsten, Rickard Ljung, Axel C Carlsson, Martin J Holzmann. International Journal of Cardiology. 2017;232:111-116.
https://doi.org/10.1016/j.ijcard.2017.01.044

III. Relation of chronic myocardial injury and non-ST-segment elevation myocardial infarction to mortality. Andreas Roos, Ulrik Sartipy, Rickard Ljung, Martin J Holzmann. [Accepted]
https://doi.org/10.1016/j.amjcard.2018.09.006

IV. Diurnal variation in admission troponin concentrations in patients with chest pain in the emergency department. Andreas Roos, Martin J Holzmann. Clinical Biochemistry. 2018;54:18-24.
https://doi.org/10.1016/j.clinbiochem.2018.02.003