sST2 Predicts Outcome in CHF Beyond NT-proBNP and hs-TnT

Study Questions:

Does soluble suppression of tumorigenesis-2 (sST2) independently predict outcomes in patients with chronic heart failure (CHF)?

Methods:

Data from 4,268 patients from six cohorts in which N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), and sST2 were measured, were included in a meta-analysis to assess the independent prognostic value of sST2 in patients with CHF. Endpoints included all-cause death, cardiovascular death, and HF hospitalization. The optimal cutoffs for receiver-operating characteristic curves were established using Youden’s J statistics. Median biomarker levels were also considered as cutoffs. The patient risk for the three endpoints was expressed as relative risk. Cox regression analysis was performed to determine the prognostic value of biomarkers.

Results:

The majority of patients were male (75%), median age 68 years, and had HF of ischemic origin (65%); 87% had a left ventricular ejection fraction (LVEF) <40%. Median concentrations of hs-TnT, NT-proBNP, and sST2 levels were 18, 1,360, and 27 ng/ml, respectively. Patients with sST2 ≥27 ng/ml were older, more often men, and less likely to have ischemic HF or a preserved EF (p < 0.001). They also had a higher body mass index, higher frequency of diabetes, worse renal function, and higher NT-proBNP and hs-TnT concentrations (p < 0.001). All-cause death occurred in 31%, cardiovascular (CV) death in 22%, and HF hospitalizations in 24%. Patients with sST2 ≥ the median had an increased risk of all-cause death, CV death, and HF hospitalization by 100%, 50%, and 10%, respectively, compared to those with no biomarker ≥ the median. Having all three biomarkers ≥ the median was also associated with an increased risk of the endpoint, 850%, 640%, and 590%, respectively. The combination of sST2 and another biomarker ≥ the median had an intermediate risk profile, and the combination of sST2 and hs-TnT ≥ the median was associated with increased risk of all-cause death. The best sST2 cutoff for the prediction of all-cause and CV death, and HF hospitalization was 28 ng/ml. sST2 was independently associated with outcomes in models that included prognostically significant baseline characteristics as well as those with all three biomarkers. When all three biomarkers were included, the risk of all-cause death, CV death, and HF hospitalization increased by 26%, 25%, and 30%, respectively, per each doubling of sST2. sST2 was prognostically significant across multiple subgroups, except patients with preserved or mid-range EF.

Conclusions:

The authors concluded that sST2 is an independent predictor of all-cause and CV mortality and CV hospitalizations in patients with CHF, and adds to the predictive value of NT-proBNP and hs-TnT.

Perspective:

Biomarkers are useful in determining prognosis in HF patients. Prospective studies should be performed to evaluate the feasibility and cost-effectiveness of a panel of biomarkers in predicting outcomes and in guiding therapy in HF patients.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Biological Markers, Body Mass Index, Carcinogenesis, Cell Transformation, Neoplastic, Diabetes Mellitus, Heart Failure, Ischemia, Natriuretic Peptide, Brain, Renal Insufficiency, Risk Factors, Stroke Volume, Troponin T


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