Multi-Marker Strategy in Heart Failure: Combination of ST2 and CRP Predicts Poor Outcome

Abstract

Natriuretic peptides (BNP and NT-proBNP) are recognized as gold-standard predictive markers in Heart Failure (HF). However, currently ST2 (member of the interleukin 1 receptor family) has emerged as marker of inflammation, fibrosis and cardiac stress. We evaluated ST2 and CRP as prognostic markers in 178 patients with chronic heart failure in comparison with other classical markers such as clinical established parameters but also biological markers: NT-proBNP, hs-cTnT alone or in combination. In multivariate analysis, subsequent addition of ST2 led to age, CRP and ST2 as the only remaining predictors of all-cause mortality (HR 1.03, HR 1.61 and HR 2.75, respectively) as well as of cardiovascular mortality (HR 1.00, HR 2.27 and HR 3.78, respectively). The combined increase of ST2 and CRP was significant for predicting worsened outcomes leading to identify a high risk subgroup that individual assessment of either marker. The same analysis was performed with ST2 in combination with Barcelona score. Overall, our findings extend previous data demonstrating that ST2 in combination with CRP as a valuable tool for identifying patients at risk of death.

Fig 1. Kaplan Meier curves for all-cause mortality based on quartiles of ST2, hs-cTnT, NT-proBNP and CRP.

Fig 2. Correlation analysis between each biomarker included in this study.

Fig 3

Association of ST2 with CRP levels dichotomized as high or low according to the median of each biomarker (A) Correlation analysis with survival rate in %, (B) Adjusted hazard ratio of death according to combined criteria as median of ST2 and CRP and (C) Kaplan Meier curves for all-cause mortality according to combination of median of ST2 and CRP and (D) Reclassification of two years risk of death for all cause or cardiovascular (CV) mortality. NRI and IDI values were reported when CRP was added to the clinical model in combination with high level of ST2. NRI: net reclassification index; IDI: integrated discrimination index.

Fig 4

Association of ST2 with Barcelona score levels dichotomized as high or low according to the median of each biomarker (A) Correlation analysis with survival rate, (B) Adjusted hazard ratio of death according to combined criteria as median of ST2 and Barcelona score (C) Kaplan Meier curves for all-cause mortality according to combination of median of ST2 and Barcelona score and (D) Reclassification of two years risk of death for all cause or cardiovascular (CV) mortality. NRI and IDI values were reported when CRP was added to the clinical model in combination with high BCN value. NRI: net reclassification index; IDI: integrated discrimination index; BCN: Barcelona bio-heart failure risk calculator (BCN Bio-HF calculator).