Predicting risk of major adverse cardiac events

Abstract

Measurement of circulating ST2 and natriuretic peptide (e.g., NT-proBNP) concentrations is useful for the prognostic evaluation of subjects, in particular for the prediction of adverse clinical outcomes, e.g., mortality, transplantation, and heart failure.

What is claimed is: 
     
         1 . A method for treating a subject comprising:
 determining a first level of soluble Growth Stimulation-Expressed Gene 2 (ST2) in a biological sample obtained from a subject at a first time point (ST2T0), a second level of soluble ST2 in a biological sample obtained from a subject at a second time point (ST2T1), and a level of natriuretic peptide (NP) in a biological sample obtained from a subject at the second time point (NPT1);   determining a MACE risk score (MACERS) for a subject utilizing, at least in part, a ratio of ST2T1 to ST2T0, in combination with a weighted logarithm of NPT1;   comparing the MACERS to a reference MACERS; and   selecting or modifying a treatment for the subject based on the comparison of the MACERS to the reference MACERS.   
     
     
         2 . The method of  claim 1 , wherein the logarithm of NPT1 includes a natural logarithm. 
     
     
         3 . The method of  claim 1 , wherein the MACERS is determined using the following formula:
   MACERS=(ST2T1/ST2T0)+α ln(NPT1),
   wherein the coefficient α is a weighting factor for the variable it acts on.   
     
     
         4 . The method of  claim 3 , wherein the coefficient α is about 0.33. 
     
     
         5 . The method of  claim 1 , wherein the NP is a brain-type natriuretic peptide (NT-proBNP). 
     
     
         6 . The method of  claim 1 , wherein the subject is already being treated and an alternative treatment is selected. 
     
     
         7 . The method of  claim 1 , wherein the subject is already being treated and the treatment is discontinued. 
     
     
         8 . The method of  claim 1 , wherein the treatment selected includes hospitalization or monitoring of the subject's cardiac status. 
     
     
         9 . The method of  claim 1 , wherein the subject is hospitalized and the subject is discharged. 
     
     
         10 . The method of  claim 1 , wherein the subject exhibits one or more non-specific symptoms. 
     
     
         11 . The method of  claim 1 , wherein the subject has a pulmonary disorder or a liver disorder. 
     
     
         12 . The method of  claim 1 , wherein the subject has been diagnosed with heart failure. 
     
     
         13 . The method of  claim 1 , wherein the biological sample obtained at the first time point or the biological sample obtained at the second time point comprises serum, blood, plasma, or urine. 
     
     
         14 . A method of identifying a subject for further diagnostic testing comprising:
 determining a first level of soluble Growth Stimulation-Expressed Gene 2 (ST2) in a biological sample obtained from a subject at a first time point (ST2T0), a second level of soluble ST2 in a biological sample obtained from a subject at a second time point (ST2T1), and a level of natriuretic peptide (NP) in a biological sample obtained from a subject at the second time point (NPT1);   determining a MACE risk score (MACERS) for a subject utilizing, at least in part, a ratio of ST2T1 to ST2T0, in combination with a weighted logarithm of NPT1;   comparing the MACERS to a reference MACERS; and   selecting a subject having an increase in the MACERS in comparison with the reference MACERS for further diagnostic testing.   
     
     
         15 . The method of  claim 14 , wherein the logarithm of NPT1 includes a natural logarithm. 
     
     
         16 . The method of  claim 14 , wherein the MACERS is determined using the following formula:
   MACERS=(ST2T1/ST2T0)+α ln(NPT1),
   wherein the coefficient α is a weighting factor for the variable it acts on.   
     
     
         17 . The method of  claim 16 , wherein the coefficient α is about 0.33. 
     
     
         18 . The method of  claim 14 , wherein the NP is brain-type natriuretic peptide (NT-proBNP). 
     
     
         19 . The method of  claim 14 , wherein the subject is undiagnosed. 
     
     
         20 . The method of  claim 14 , wherein the further diagnostic testing comprises imaging studies, cardiac catheterization, measuring lung function, or measuring renal function. 
     
     
         21 . The method of  claim 14 , wherein the further diagnostic testing comprises determining a level of one or more additional biomarkers selected from the group consisting of: cardiac troponin I, D-dimers, C-reactive protein, alanine transaminase, aspartate transaminase, alkaline phosphatase, bilirubin, interleukin-6, blood urea nitrogen, albumin, creatinine, bacterial endotoxin, creatinine clearance rate, and glomerular filtration rate. 
     
     
         22 . The method of  claim 14 , wherein the biological sample obtained at the first time point or the biological sample obtained at the second time point comprises serum, blood, plasma, or urine. 
     
     
         23 . A method of evaluating risk of death within a specific time period comprising:
 determining a first level of soluble Growth Stimulation-Expressed Gene 2 (ST2) in a biological sample obtained from a subject at a first time point (ST2T0), a second level of soluble ST2 in a biological sample obtained from a subject at a second time point (ST2T1), and a level of natriuretic peptide (NP) in a biological sample obtained from a subject at the second time point (NPT1);   determining a MACE risk score (MACERS) for a subject utilizing, at least in part, a ratio of ST2T1 to ST2T0, in combination with a weighted logarithm of NPT1;   comparing the MACERS to a reference MACERS;   determining a level of an adjunct biomarker in the biological sample obtained from the subject at the first time point or the biological sample obtained from the subject at the second time point; and   comparing the level of the adjunct biomarker to a reference level of the adjunct biomarker;   wherein the MACERS in comparison with the reference MACERS, and the level of the adjunct biomarker in comparison with the reference level of the adjunct biomarker is indicative of the subject's risk of death within a specific time period.   
     
     
         24 . The method of  claim 23 , wherein the logarithm of NPT1 includes a natural logarithm. 
     
     
         25 . The method of  claim 23 , wherein the MACERS is determined using the following formula:
   MACERS=(ST2T1/ST2T0)+α ln(NPT1),
   wherein the coefficient α is a weighting factor for the variable it acts on.   
     
     
         26 . The method of  claim 25 , wherein the coefficient α is about 0.33. 
     
     
         27 . The method of  claim 23 , wherein the NP is brain-type natriuretic peptide (NT-proBNP). 
     
     
         28 . The method of  claim 23 , wherein the reference MACERS is a MACERS of a subject or group of subjects having a low risk of a MACE within one year. 
     
     
         29 . The method of  claim 23 , wherein the specific time period is one year. 
     
     
         30 . The method of  claim 23 , wherein the subject exhibits one or more non-specific symptoms. 
     
     
         31 . The method of  claim 23 , wherein the subject has a pulmonary disorder or a liver disorder. 
     
     
         32 . The method of  claim 23 , wherein the subject has been diagnosed with heart failure. 
     
     
         33 . The method of  claim 23 , wherein the adjunct biomarker is selected from the group consisting of: cardiac troponin I, D-dimers, C-reactive protein, alanine transaminase, aspartate transaminase, alkaline phosphatase, bilirubin, interleukin-6, blood urea nitrogen, albumin, creatinine, bacterial endotoxin, creatinine clearance rate, and glomerular filtration rate. 
     
     
         34 . The method of  claim 23 , wherein the biological sample obtained at the first time point or the biological sample obtained at the second time point comprises serum, blood, plasma, or urine.