High-Sensitivity Cardiac Troponin I Measurement for Risk Stratification in a Stable High-Risk Population

Study Questions:

Can a high-sensitivity cardiac troponin I (hs-cTnI) assay predict ischemic cardiovascular events in a stable high-risk population?

Methods:

Prior studies have focused primarily on early identification of acute coronary syndromes (ACS) using hs-TnI assays, with less information in stable coronary artery disease (CAD) patients. An investigational hs-TnI assay (Beckman Coulter) was used in 2,572 participants from the HOPE study. Enrollment criteria for this study included age ≥55 with a history of CAD, stroke, diabetes, or peripheral vascular disease and at least one additional CAD risk factor, and no heart failure. The derived receiver operating characteristic (ROC) curve cutoff and the 99th percentile for the hs-cTnI assay were calculated for the primary outcome (composite of myocardial infarction [MI], stroke, and cardiovascular death) at 4.5 years of follow-up. In addition, individual outcomes (MI, stroke, cardiovascular death) and the combined outcome (MI/cardiovascular death) were also assessed in models that included established risk factors, C-reactive protein, and NT-proBNP.

Results:

An hs-TnI concentration of 6 ng/L had the highest area under the curve by ROC curve analysis (50% of the study cohort), with 22% having a value >10 ng/L (99th percentile). Participants with hs-cTnI >6 ng/L were at higher risk for the primary outcome (hazard ratio [HR], 1.4; 95% confidence interval [CI], 1.1-1.8; p = 0.008, adjusted models). For individual outcomes, participants with hs-cTnI above ≥10 ng/L had higher risk for cardiovascular death (HR, 2.2; 95% CI, 1.3-3.5; p = 0.002) and MI (HR, 1.5; 95% CI, 1.1-2.1; p = 0.03), but not stroke (HR, 1.4; 95% CI, 0.8-2.5; p = 0.29, adjusted models). Addition of hs-cTnI to an established risk model with NT-proBNP increased the c-statistic for the combined outcome of MI/cardiovascular death (from 0.66 to 0.68; p = 0.02).

Conclusions:

The investigational Beckman Coulter hs-cTnI assay provides prognostic information for future MI and cardiovascular death, but not stroke, in a stable high-risk population.

Perspective:

This is another analysis, similar to the one done with hs-cTnT in the PEACE trial, showing the prognostic significance of hs-cTnI in defining risk in the HOPE trial cohort. Twenty-two percent of patients had values above the 99th% upper reference limit; however, even the tertile below that value was at significant increased risk despite extensive multivariate correction. These data add to the robust literature now extant indicating that hs-Tn assays will have a major role in predicting events in putatively stable individuals.

Keywords: Coronary Artery Disease, Stroke, Acute Coronary Syndrome, Myocardial Infarction, Troponin T, Peripheral Vascular Diseases, Biomarkers, Troponin I, Cardiology, Heart Failure, Peptide Fragments, Confidence Intervals, Diabetes Mellitus, Natriuretic Peptide, Brain


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