Association of Serial High-Sensitivity Cardiac Troponin T With Subsequent Cardiovascular Events in Patients
Siddharth M Patel1,2, Arman Qamar3, Robert P Giugliano1,2
1Thrombolysis in Myocardial Infarction Clinical Trials (TIMI) Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Insights
Changes in high-sensitivity troponin T (hsTnT) levels after acute coronary syndrome (ACS) predict future cardiovascular events. Rising hsTnT indicates significantly higher risk, while decreasing levels suggest similar or lower risk, aiding in patient stratification.
Area of Science:
- Cardiology
- Biomarker Research
- Clinical Trials
Background:
- Single high-sensitivity troponin (hsTn) measures link to cardiovascular events in chronic coronary syndromes.
- Limited data exist on serial hsTn changes and cardiovascular events in this population.
Purpose of the Study:
- To assess the association between changes in high-sensitivity troponin T (hsTnT) and subsequent cardiovascular events.
- To evaluate hsTnT changes in patients stabilized after acute coronary syndrome (ACS).
Main Methods:
- Secondary analysis of the IMPROVE-IT randomized clinical trial (N=6035).
- Measured hsTnT at months 1 and 4 post-ACS.
- Used landmark analyses to examine associations between hsTnT changes and composite cardiovascular outcomes.
Main Results:
- An absolute hsTnT increase of ≥7 ng/L was linked to a >3-fold higher risk of cardiovascular events (aHR, 3.33).
- Decreases in hsTnT of ≥7 ng/L showed similar or lower risk (aHR, 0.51).
- A stepwise association was observed between hsTnT change magnitude and future cardiovascular risk.
Conclusions:
- Serial hsTnT changes are associated with a gradient of cardiovascular event risk in stable post-ACS patients.
- Serial hsTnT assessment can refine risk stratification and potentially guide therapy decisions.
Importance:
Studies have demonstrated an association between single measures of high-sensitivity troponin (hsTn) and future cardiovascular events in patients with chronic coronary syndromes. However, limited data exist regarding the association between changes in serial values of hsTn and subsequent cardiovascular events in this patient population.
Objective:
To evaluate the association between changes in high-sensitivity troponin T (hsTnT) and subsequent cardiovascular events in patients stabilized after acute coronary syndrome (ACS).
Design, Setting, And Participants:
This is a secondary analysis from the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), a randomized clinical trial of ezetimibe vs placebo on a background of simvastatin in 18 144 patients hospitalized for an ACS across 1147 sites in 39 countries. The current biomarker substudy includes the 6035 participants consenting to the biomarker substudy with available hsTnT at months 1 and 4. Data were collected from October 26, 2005, through July 8, 2010, with the database locked October 21, 2014. Data were analyzed from February 28, 2021, through August 14, 2022.
Main Outcomes And Measures:
The outcomes of interest were cardiovascular death, myocardial infarction (MI), stroke, or hospitalization for heart failure (HHF). Associations of absolute and relative changes in hsTnT between month 1 and month 4 as a function of the starting month 1 hsTnT and the composite outcome were examined using landmark analyses.
Results:
Of 6035 patients in this analysis (median [IQR] age, 64 [57-71]), 1486 (24.6%) were female; 361 (6.0%) were Asian; 121 were (2.0%) Black; 252 (4.2%) were Spanish descent; 4959 were (82.2%) White; and 342 (5.7%) reported another race (consolidated owing to small numbers), declined to respond, or were not asked to report race owing to regulatory prohibitions. Most patients (4114 [68.2%]) had stable hsTnT values (change <3 ng/L), with 1158 (19.2%) and 763 (12.6%) having changes of 3 to less than 7 ng/L and 7 ng/L or more, respectively. After adjustment for clinical risk factors and stratification by the starting month 1 hsTnT level, an absolute increase in hsTnT of 7 ng/L or more was associated with a more than 3-fold greater risk of the composite outcome (adjusted hazard ratio [aHR], 3.33; 95% CI, 1.99-5.57; P < .001), whereas decreases of 7 ng/L or more were associated with similar to lower risk (aHR, 0.51; 95% CI, 0.26-1.03; P = .06) compared with stable values. There was a stepwise association moving from larger absolute decreases (aHR, 0.51; 95% CI, 0.26-1.03) to larger absolute increases (aHR, 3.33; 95% CI, 1.99-5.57) in hsTnT with future risk of the composite outcome (P trend <.001). A similar association was observed when analyzed on the basis of relative percent and continuous change.
Conclusions And Relevance:
Among stable patients post-ACS, changes in hsTnT were associated with a gradient of risk of subsequent cardiovascular events across the range of starting hsTnT values. Serial assessment of hsTnT may refine risk stratification with the potential to guide therapy decisions in this patient population.
Trial Registration:
ClinicalTrials.gov Identifier: NCT00202878.
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