Changes in serial hsTnT associated with risk of subsequent CV events in stabilized ACS
Association of serial high-sensitivity cardiac troponin T with subsequent cardiovascular events in patients stabilized after acute coronary syndrome: a secondary analysis from IMPROVE-IT
Introduction and methods
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 . 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 .
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.
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.
The outcomes of interest were the composite of CV death, myocardial infarction, stroke, or hospitalization for HF, and the individual end point components.
- 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).
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.