Single-Molecule hsTnI and Short-Term Risk in Stable Patients With Chest Pain

Abstract

Background: Evaluation of stable symptomatic outpatients with suspected coronary artery disease (CAD) may be challenging because they have a wide range of cardiovascular risk. The role of troponin testing to assist clinical decision making in this setting is unexplored.

Objectives: This study sought to evaluate the prognostic meaning of single-molecule counting high-sensitivity troponin I (hsTnI) (normal range <6 ng/l) among outpatients with stable chest symptoms and suspected CAD.

Methods: Participants with available blood samples in PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) were studied, and hsTnI results were analyzed relative to the primary outcome of death, acute myocardial infarction (MI), or hospitalization for unstable angina by 1 year. The secondary outcome was the composite of cardiovascular death or acute MI.

Results: The study sample consisted of 4,021 participants; 98.6% had measurable hsTnI concentrations. The median hsTnI value was 1.6 ng/l. In upper hsTnI quartiles, patients had higher-risk clinical profiles. Higher hsTnI concentrations were associated with greater event probabilities for death, acute MI, or hospitalization for unstable angina. In multivariable models, hsTnI concentrations independently predicted death, acute MI, or hospitalization for unstable angina (hazard ratio: 1.54 per increase in log-hsTnI interquartile range; p < 0.001) and cardiovascular death or acute MI (hazard ratio: 1.52 per increase in log-hsTnI interquartile range; p < 0.001) and were particularly associated with near-term events, compared with longer follow-up.

Conclusions: In symptomatic outpatients with suspected CAD, higher concentrations of hsTnI within the normal range were associated with heightened near-term risk for death, acute MI, or hospitalization. (Prospective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550).

Keywords: chest pain; stable angina; troponin.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

FIGURE 1. Study Flow for the Present Analysis

Of an original 10,003 participants, 4,021 were included. hsTnI = high-sensitivity troponin I; PROMISE = Prospective Multicenter Imaging Study for Evaluation of Chest Pain.

FIGURE 2. Cumulative Hazard Curves Depicting Time-to-Events as a Function of hsTnI Quartiles at Presentation

(A) Death, acute myocardial infarction, or hospitalization for unstable angina at 1 year. (B) Cardiovascular death or acute myocardial infarction at 1 year. The insets detail outcomes to 3 years of follow-up. Outcomes are depicted to 12 months; insets demonstrate outcomes through complete follow-up of the PROMISE trial. Q = quartile; other abbreviations as in Figure 1.

CENTRAL ILLUSTRATION. Previous Data Suggest Concentrations of hsTnI Predict Presence and Severity of Underlying Coronary Artery Disease

In the present analysis, we found that high-sensitivity troponin I (hsTnI) concentrations predicted risk for incident death, myocardial infarction (MI), or hospitalization for unstable angina in a graded fashion. In adjusted analyses, high-sensitivity troponin I represented a strong independent predictor of these outcomes, and did so by predicting earlier rather than later events. These results suggest a possible role for measurement of troponin I using a very highly sensitive assay as a part of an overall strategy for evaluation of stable chest symptoms and possible coronary artery disease.