Early troponin I in critical illness and its association with hospital mortality: a cohort study

Abstract

Background: Troponin I (TnI) is frequently elevated in critical illness, but its interpretation is unclear. Our primary objectives in this study were to evaluate whether TnI is associated with hospital mortality and if this association persists after adjusting for potential confounders. We also aimed to ascertain whether addition of TnI to the Acute Physiological and Chronic Health Evaluation II (APACHE II) risk prediction model improves its performance in general intensive care unit (ICU) populations.

Methods: We performed an observational cohort study with independent derivation and validation cohorts in two general level 3 ICU departments in the United Kingdom. The derivation cohort was a 4.5-year cohort (2010-2014) of general ICU index admissions (n = 1349). The validation cohort was used for secondary analysis of a prospective study dataset (2010) (n = 145). The primary exposure was plasma TnI concentration taken within 24 h of ICU admission. The primary outcome was hospital mortality. We performed multivariate regression, adjusting for components of the APACHE II model. We derived the risk prediction score from the multivariable model with TnI.

Results: Hospital mortality was 37.3% (n = 242) for patients with detectable TnI, compared with 14.6% (n = 102) for patients without detectable TnI. There was a significant univariate association between TnI and hospital mortality (OR per doubling TnI 1.16, 95% CI 1.13-1.20, p < 0.001). This persisted after adjustment for APACHE II model components (TnI OR 1.05, 95% CI 1.01-1.09, p = 0.003). TnI correlated most strongly with the acute physiology score (APS) component of APACHE II (r = 0.39). Addition of TnI to the APACHE II model did not improve discrimination (APACHE II concordance statistic [c-index] 0.835, 95% CI 0.811-0.858; APACHE II + TnI c-index 0.837, 95% CI 0.813-0.860; p = 0.330) or other measures of model performance.

Conclusions: TnI is an independent predictor of hospital mortality and correlates most highly with the APS component of APACHE II. It does not improve risk prediction. We would not advocate the adoption of routine troponin analysis on admission to ICU, and we recommend that troponin be measured only if clinically indicated.

Keywords: Critical care; Hospital mortality; Troponin.

Fig. 1

Flow of patients through study. GRI Glasgow Royal Infirmary, ICU Intensive care unit, TnI Troponin I

Fig. 2

Association between troponin I (TnI; in μg/L) and hospital mortality. a Univariate association (OR per doubling of TnI 1.16, 95% CI 1.13–1.20, p < 0.001). b Multivariate association between TnI and hospital mortality once added to the Acute Physiological and Chronic Health Evaluation II model (OR 1.05, 95% CI 1.01–1.09, p < 0.001)

Fig. 3

ROC curves: Acute Physiological and Chronic Health Evaluation (APACHE) (black solid line; concordance statistic [c-index] 0.847), APACHE + troponin (red dashed line; c-index 0.846) and troponin I (green dashed line; c-index 0.696)

Fig. 4

Sensitivity and subgroup analyses. OR of hospital mortality for doubling of TnI as a continuous variable for different subgroups after adjusting for the Acute Physiological and Chronic Health Evaluation II (APACHE II) risk prediction model. ‘Whole cohort categorical’ refers to TnI entered as a binary variable: TnI + ve vs TnI − ve using the threshold of the limits of detection (0.04). LL Lower limit of 95% CI, UL Upper limit of 95% CI, NYHA New York Heart Association cardiac disease class IV (APACHE II classification for severe cardiac disease)