Prognostic value of soluble ST2 biomarker in heart failure patients with obstructive sleep apnea syndrome
Authors: Kopeva K , Grakova EV , Yakovlev AV , Shilov SN , Yakovleva NF , Berezikova EN , Teplyakov AT 
Published: July 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.
Objective. To analyze the relationships between soluble ST2 (sST2) levels, apnea/hypopnea index (AHI) and echocardiographic parameters in heart failure patients with preserved ejection fraction (HFpEF) and to evaluate prognostic values of sST2 in the development of adverse cardiac events (ASE) during the 12-month follow-up period. Methods. A total of 86 men, median age of 62.0 (41.0; 78.0) years with obstructive sleep apnea syndrome (OSAS) and HF of NYHA class I-III with baseline LVEF of 60% [52; 65]% were enrolled in the study. The severity of obstructive breathing disorders during sleep was assessed by AHI. Serum levels of NT-proBNP and sST2 were measured using ELISA at baseline. Two-dimensional transthoracic echocardiography with assessment of right ventricular (RV) function and 6-minute walk test (6MWT) were performed at baseline. Results. The values of AHI significantly correlated with body mass index (r = 0.362), left atrial volume (r = 0.570), fractional change in the area of the RV (r=-0.527), RV myocardial function index (r=-0.377), NT-proBNP (r = 0.611), 6MWT (r=-0.511), RV anterior wall thickness (r = 0,472), while the levels of sST2 significantly correlated with LV remodeling parameters: LVEF (r =-0.301), end-systolic volume (r =0.453), end-diastolic volume (r =0.396), end-systolic dimension (r = 0.373), end-diastolic dimension (r =0.288). Based on ROC-analysis, sST2 ≥29.67 ng/mL (sensitivity 63.6%, specificity 73.6%, AUC = 0.645; p &lt; 0.0001) were identified as a cut-off values predicting the development of ACE. At 12 months of follow-up period all patients were divided into 2 groups according to cut-off values of sST2: group 1 (n = 29) comprised patients with sST2 ≥29.67 ng/mL, group 2 (n = 42) comprised patients with sST2 &lt;29.67 ng/mL. The median baseline values of sST2 were 41.39 [33.31; 50.99] ng/mL in group 1, and 22.18 [20.64; 25.5] ng/mL in group 2. The concentrations of NT-proBNP did not differ between the groups. During the 12-month follow-up period in group 1 the rate of ACE was 29.7% cases, and 5.2% in group 2, respectively. According to Kaplan-Meier analysis, a higher sST2 levels was associated with a higher frequency of ACE during 12 months of follow-up (р&lt;0.0001). Univariable and multivariable Cox regression analyses showed sST2 concentrations were significantly associated with ACE (odds ratio 2.25, 95%CI: 2.06 to 3.29, p &lt; 0.001), when adding AHI and LV myocardial mass index improved reclassification of risk stratification (odds ratio 3,28, 95%CI: 3,09 to 4,49, p &lt; 0.001, AUC of 0.945, percent of cases correctly classified of 90.14 %). However, NT-proBNP addition had a limited effect on risk stratification. Conclusion. Our data suggest that sST2 may be used as a diagnostic biomarker for prediction of ACE in patients with HFpEF and OSAS during the 12-month follow-up period. The combined evaluation of sST2, AHI and LV myocardial mass index values demonstrated higher diagnostic sensitivity and specificity for prediction of ACE.