Multimarker Risk Stratification

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 evaluating the risk of mortality for a subject within one year, the method comprising:
 determining a multimarker mortality risk score for a subject based upon:
 the age of the subject; 
 the level of ST2 in the subject, in combination with one or more of a natural logarithm of a level of a brain natriuretic peptide (BNP) in the subject; a level of troponin in the subject; a New York Heart Association (NYHA) score; a history of cardiovascular disease (CAD); a natural logarithm of a systolic blood pressure; a measure of renal function or a natural logarithm of a level of hemoglobin (Hgb), age; and 
   comparing the multimarker mortality risk score to a reference multimarker mortality risk score;   wherein the presence of a multimarker mortality risk score that is at or above the reference multimarker mortality risk score indicates that the subject has an increased risk of mortality within one year.   
     
     
         2 . The method of  claim 1 , wherein the risk score is determined using one of the following algorithms:
   AGE+ST2+ln_SBP+CAD+ln_NTpro-BNP  (9)
     AGE+ST2+ln_NTpro-BNP  (10)
     AGE+ST2+Troponin+NYHA  (11)
     AGE+ST2+[Troponin OR NYHA]  (12)
     AGE+ST2+[Troponin AND/OR NYHA]+ln_Hgb  (13)
     AGE+ST2+[Troponin AND/OR NYHA]+ln_Hgb  (14)
     AGE+ST2+[Troponin AND/OR NYHA]+ln_Hgb+ln_SBP  (15)
     AGE+ST2+[Troponin AND/OR NYHA]+ln_Hgb+ln_SBP+ln_NTpro-BNP  (16)
   
     
     
         3 . The method of  claim 2 , wherein the level of ST2 is determined and compared to a threshold and the presence of a level at or above the threshold is scored as “1” and the presence of a level below the threshold is scored as “0”. 
     
     
         4 . The method of  claim 3 , wherein the threshold is 35 or 50 ng/mL. 
     
     
         5 . The method of  claim 4 , wherein algorithm (1) or (2) is used and the threshold level of ST2 is 35 ng/ml. 
     
     
         6 . The method of  claim 4 , wherein algorithm (3) or (4) is used and the threshold level of ST2 is 50 ng/ml. 
     
     
         7 . The method of  claim 1 , wherein the subject has been diagnosed with heart failure. 
     
     
         8 . The method of  claim 1 , wherein the reference multimarker mortality risk score represents a score corresponding to a low risk of death within one year or within five years. 
     
     
         9 . The method of  claim 1 , wherein the sample comprises serum, blood, plasma, urine, or body tissue. 
     
     
         10 . The method of  claim 1 , wherein the subject has a BMI of 25-29, a BMI of ≧30, or renal insufficiency. 
     
     
         11 . The method of  claim 1 , further comprising discharging the subject or treating the subject on an inpatient basis based on the presence of an increased risk of mortality.