Predicting mortality and detecting severe disease

Abstract

Measurement of circulating ST2 and/or IL-33 concentrations is useful for the prognostic evaluation of subjects, in particular for the prediction of adverse clinical outcomes, e.g., mortality, and the detection of severe disease.

1 . (canceled) 
     
     
         2 . A method for evaluating the risk of death within 30 days for a subject having heart failure, and treating the subject, the method comprising:
 (a) determining a level of soluble ST2 in a biological sample from the subject;   (b) identifying a subject having a level of soluble ST2 that is equal or elevated as compared to a reference level of soluble ST2 as having an elevated risk of death within 30 days; and   (c) administering a treatment to the subject identified as having an elevated risk of death within 30 days, wherein the treatment is selected from the group consisting of inpatient treatment and cardiac catheterization.   
     
     
         3 . The method of  claim 2 , wherein the reference level of soluble ST2 is a threshold level. 
     
     
         4 . The method of  claim 2 , wherein the reference level of soluble ST2 is a level of ST2 present in a subject who has no disease or no acute disease. 
     
     
         5 . The method of  claim 2 , wherein the biological sample comprises serum, blood, or plasma. 
     
     
         6 . The method of  claim 2 , further comprising:
 determining the level of one or more adjunct biomarker(s) in the sample, wherein the one or more adjunct biomarker(s) is selected from the group consisting of troponin, brain natriuretic peptide (BNP), proBNP, NT-proBNP, atrial natriuretic peptide (ANP), NT-proANP, proANP, C-reactive peptide (CRP), and D-dimers; and   further identifying a subject having an elevated level of the one or more adjunct biomarker(s) in the sample as compared to a reference level(s) of the one or more adjunct biomarkers as having an increased risk of death within 30 days.   
     
     
         7 . The method of  claim 6 , wherein the one or more adjunct biomarker(s) is selected from the group consisting of: NT-proBNP and BNP. 
     
     
         8 . The method of  claim 2 , wherein the subject has a body mass index (BMI) of 25-29, a BMI of 30, or renal insufficiency. 
     
     
         9 . The method of  claim 2 , wherein step (a) comprises performing an immunoassay to determine the level of soluble ST2. 
     
     
         10 . The method of  claim 9 , wherein the immunoassay is an enzyme-linked immunosorbent assay (ELISA). 
     
     
         11 . The method of  claim 9 , wherein the immunoassay utilizes a monoclonal antibody. 
     
     
         12 . A method of evaluating the risk of death within 30 days for a subject having heart failure, and treating the subject, the method comprising:
 (a) determining a first level of soluble ST2 in a biological sample obtained from the subject at a first time point;   (b) determining a second level of soluble ST2 in a biological sample obtained from the subject at a second time point;   (c) identifying a subject having a second level of soluble ST2 that is equal or elevated as compared to the first level of ST2 as having an elevated risk of death within 30 days; and   (e) administering a treatment to the subject identified as having an elevated risk of death within 30 days, wherein the treatment is selected from the group consisting of inpatient treatment and cardiac catheterization.   
     
     
         13 . The method of  claim 12 , wherein at least two days pass between the first time point and the second time point. 
     
     
         14 . The method of  claim 12 , wherein the biological sample obtained from the subject at the first time point and the biological sample obtained from the subject at the second time point each comprise serum, blood, or plasma. 
     
     
         15 . The method of  claim 12 , further comprising:
 determining a first level of one or more adjunct biomarker(s) in the biological sample obtained from the subject at the first time point, wherein the one or more adjunct biomarker(s) is selected from the group consisting of troponin, brain natriuretic peptide (BNP), proBNP, NT-proBNP, atrial natriuretic peptide (ANP), NT-proANP, proANP, C-reactive peptide (CRP), and D-dimers;   determining a second level of one or more adjunct biomarker(s) in the biological sample obtained from the subject at the second time point, wherein the one or more adjunct biomarker(s) is selected from the group consisting of troponin, brain natriuretic peptide (BNP), proBNP, NT-proBNP, atrial natriuretic peptide (ANP), NT-proANP, proANP, C-reactive peptide (CRP), and D-dimers; and   further identifying a subject having an elevated second level of the one or more adjunct biomarker(s) in the sample as compared to the first level of the one or more adjunct biomarker(s) of the one or more adjunct biomarkers as having an increased risk of death within 30 days.   
     
     
         16 . The method of  claim 13 , wherein the one or more adjunct biomarker(s) is selected from the group consisting of: NT-proBNP and BNP. 
     
     
         17 . The method of  claim 12 , wherein the subject has a body mass index (BMI) of 25-29, a BMI of ≥30, or renal insufficiency. 
     
     
         18 . The method of  claim 12 , wherein step (a) and step (b) comprises performing an immunoassay to determine the first level and second level of soluble ST2, respectively. 
     
     
         19 . The method of  claim 17 , wherein the immunoassay is an enzyme-linked immunosorbent assay (ELISA). 
     
     
         20 . The method of  claim 19 , wherein the immunoassay utilizes a monoclonal antibody.