Changes in serial hsTnT associated with risk of subsequent CV events in stabilized ACS
The IMPROVE-IT trial showed that a single measurement of hsTnT levels 1 month after stabilization post-ACS was associated with the risk of subsequent CV events. Can serial assessment of hsTnT levels further refine risk stratification?
Association of serial high-sensitivity cardiac troponin T with subsequent cardiovascular events in patients stabilized after acute coronary syndrome: a secondary analysis from IMPROVE-ITLiterature - Patel SM, Qamar A, Giugliano RP, et al. - JAMA Cardiol. 2022 Dec 1;7(12):1199-1206. doi: 10.1001/jamacardio.2022.3627.
Introduction and methods
Background
Determination of high-sensitivity troponin-T (hsTnT) levels plays a role not only in the diagnosis of ACS, but also in risk stratification for secondary prevention in CVD [1-6]. For example, reclassification based on hsTnT levels may be useful to guide intensive blood pressure and lipid lowering [5,7]. In patients with DM and ischemic heart disease, small absolute changes in serial hsTnT provided incremental prognostic information [8]. However, data on the implications of such changes in patients with ACS are limited. A previous secondary analysis of the IMPROVE-IT trial showed that in these patients, a single measurement of hsTnT levels 1 month after stabilization post-ACS was associated with the risk of subsequent CV events [1].
Aim of the study
This secondary analysis of the IMPROVE-IT trial examined the association of changes in serial hsTnT with the risk of subsequent CV events in high-risk patients with stabilized ACS.
Methods
The IMPROVE-IT trial is an international, multicenter, double-blind RCT in which 18,144 patients with stabilized ACS were randomized to ezetimibe or placebo, in addition to simvastatin. Patients aged 50 years or older who had been hospitalized in the past 10 days because of STEMI, NSTEMI, or unstable angina were eligible to participate if they had at least 1 high-risk factor and LDL-c levels of 50-125 mg/dL (or 50-100 mg/dL for patients receiving chronic statin therapy), and were stabilized for at least 24 hours prior to randomization. This secondary analysis involved 6035 patients (24.6% female) in whom hsTnT levels were measured at 1 and 4 months. The median follow-up was 6 years.
Outcomes
The outcomes of interest were the composite of CV death, myocardial infarction, stroke, or hospitalization for HF, and the individual end point components.
Main results
- In most patients (68.2%), hsTnT levels remained stable over time (change <3 ng/L), whereas 19.2% and 12.6% of patients had absolute changes of 3 to less than 7 ng/L and ≥7 ng/L, respectively.
- After adjustment for clinical risk factors and stratification by hsTnT levels at 1 month, an absolute increase in hsTnT levels ≥7 ng/L was associated with a more than 3-fold increased risk of the composite outcome (aHR: 3.33; 95%CI: 1.99-5.57; P<0.001), whereas an absolute decrease ≥7 ng/L was associated with a similar to lower risk (aHR: 0.51; 95%CI: 0.26-1.03; P=0.06), compared with stable hsTnT levels.
- 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 the risk of the composite outcome (P trend <0.001); this graded association was consistent when stratifying by hsTnT levels at 1 month and for the individual end point components.
- A ≥50% increase in hsTnT levels was associated with an approximately 2-fold increased risk of the composite outcome (aHR: 2.09; 95%CI: 1.60-2.73; P<0.001), compared with stable hsTnT levels.
- When considered as a continuous variable, an increase or decrease in hsTnT levels was associated with higher or lower risk of the composite outcome, respectively (aHR: 1.50; 95%CI: 1.37-1.64 per doubling of hsTnT levels; P<0.001).
Conclusion
This secondary analysis of the IMPROVE-IT trial shows a graded association of changes in serial hsTnT levels with the risk of subsequent CV events in high-risk patients with stabilized ACS. This association is independent of hsTnT concentration at 1 month.
References
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2. Eisen A, Bonaca MP, Jarolim P, et al. High-sensitivity troponin I in stable patients with atherosclerotic disease in the TRA 2°P - TIMI 50 trial. Clin Chem. 2017;63(1):307-315.
3. Omland T, de Lemos JA, Sabatine MS, et al; Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) Trial Investigators. A sensitive cardiac troponin T assay in stable coronary artery disease. N Engl J Med. 2009;361(26):2538-2547.
4. Everett BM, Brooks MM, Vlachos HEA, Chaitman BR, Frye RL, Bhatt DL; BARI 2D Study Group. Troponin and cardiac events in stable ischemic heart disease and diabetes. N Engl J Med. 2015;373(7):610-620.
5. Marston NA, Bonaca MP, Jarolim P, et al. Clinical application of high-sensitivity troponin testing in the atherosclerotic cardiovascular disease framework of the current cholesterol guidelines. JAMA Cardiol. 2020;5(11):1255-1262.
6. Ruff CT, Giugliano RP, Braunwald E, et al. Cardiovascular biomarker score and clinical outcomes in patients with atrial fibrillation: a subanalysis of the ENGAGE AF-TIMI 48 randomized clinical trial. JAMA Cardiol. 2016;1(9):999-1006.
7. Pandey A, Patel KV, VongpatanasinW, et al. Incorporation of biomarkers into risk assessment for allocation of antihypertensive medication according to the 2017 ACC/AHA High Blood Pressure Guideline: a pooled cohort analysis. Circulation. 2019;140(25):2076-2088.