Use of biomarkers in the assessment of the early transition from arterial hypertension to heart failure

Abstract

Methods and systems for diagnosing functional and/or structural abnormalities of the heart preceding heart failure, and for predicting the risk of developing heart failure, in a subject comprising measuring a cardiac troponin in a sample and comparing the measurement to a reference value. Other markers, including GDF15 and IGFBP7 are also measured in some embodiments.

What is claimed is: 
     
         1 . A method of diagnosing a heart functional or structural abnormality preceding heart failure in a subject, the method comprising the steps of:
 a) contacting, in vitro, a portion of a sample of the subject with an antibody having specific binding affinity for an epitope of a cardiac troponin marker or variant thereof, whereby a complex of the antibody and the cardiac troponin marker or variant thereof is formed;   b) calculating a concentration of the cardiac troponin marker or variant thereof in the sample based on an amount of complex formed in said step of contacting;   c) comparing the concentration of the cardiac troponin marker or variant thereof determined in said step of calculating with a cardiac troponin marker reference value; and   d) diagnosing a heart functional or structural abnormality preceding heart failure in the subject if the concentration of the cardiac troponin marker or variant thereof in the sample is greater than the cardiac troponin marker reference value.   
     
     
         2 . The method of  claim 1 , wherein the sample is selected from the group consisting of blood, serum and plasma. 
     
     
         3 . The method of  claim 1 , wherein the antibody comprises a detectable label. 
     
     
         4 . The method of  claim 3 , wherein the detectable label is one of a radioactive and a fluorescent label. 
     
     
         5 . The method of  claim 1 , further comprising the step of contacting, in vitro, a portion of the sample of the subject with a second antibody having specific binding affinity for a second epitope of the cardiac troponin marker or variant thereof, whereby a complex of the antibody, the cardiac troponin marker or variant thereof, and the second antibody is formed. 
     
     
         6 . The method of  claim 5 , wherein the second antibody comprises a detectable label. 
     
     
         7 . The method of  claim 6 , wherein the detectable label is one of a radioactive and a fluorescent label. 
     
     
         8 . The method of  claim 5 , wherein the cardiac troponin marker or variant thereof is cardiac troponin T marker or variant thereof. 
     
     
         9 . The method of  claim 8 , wherein the epitope of the cardiac troponin marker or variant thereof consists of amino acids 125-131 and the second epitope of the cardiac troponin marker or variant thereof consists of amino acids 136-147. 
     
     
         10 . The method according to  claim 1 , wherein the cardiac troponin marker or variant thereof is cardiac troponin I or a variant thereof. 
     
     
         11 . The method according to  claim 1 , wherein prior to performing steps a)-d), the subject is known to suffer from one of hypertension and diabetes. 
     
     
         12 . The method of  claim 1 , wherein the functional and/or structural abnormality is an increased septum diameter. 
     
     
         13 . The method of  claim 1 , wherein the cardiac troponin reference value is an amount at least 20% greater than a concentration of the cardiac troponing marker of a population of healthy individuals. 
     
     
         14 . The method of  claim 1 , wherein the antibody is bound to a solid phase and the second antibody is not bound to a solid phase. 
     
     
         15 . The method of  claim 1 , further comprising the steps of:
 contacting, in vitro, a portion of the sample of the subject with an antibody having specific binding affinity for an epitope of insulin-like growth factor-binding protein 7 marker or variant thereof, whereby a complex of the antibody and the insulin-like growth factor-binding protein 7 marker or variant thereof is formed;   calculating a concentration of the insulin-like growth factor-binding protein 7 marker or variant thereof in the sample based on an amount of complex formed in said step of contacting; and   comparing the concentration of the insulin-like growth factor-binding protein 7 marker or variant thereof to an insulin-like growth factor-binding protein 7 reference value,   
       wherein said step of diagnosing further comprises diagnosing a heart functional or structural abnormality preceding heart failure in the subject only if the concentration of the cardiac troponin marker or variant thereof in the sample is greater than the cardiac troponin marker reference value and the concentration of the insulin-like growth factor-binding protein 7 marker of variant thereof in the sample is greater than the insulin-like growth factor-binding protein 7 reference value. 
     
     
         16 . A device adapted for diagnosing a heart functional or structural abnormality preceding heart failure in a subject, the device comprising:
 means for determining an amount of a cardiac troponin marker of variant thereof in a sample from the subject,   implemented rules for comparing the determined amount of the cardiac troponin marker of variant thereof to a cardiac troponin marker reference value, the cardiac troponin marker reference value existing as a stored value; and   means for implementing the rules, wherein an amount of the cardiac troponin marker or variant thereof greater than the cardiac troponin marker reference value is indicative of a heart functional or structural abnormality preceding heart failure.   
     
     
         17 . The device of  claim 16 , wherein the sample is one of blood, plasma and serum. 
     
     
         18 . The device of  claim 16 , wherein said means for determining the amount of the cardiac troponin marker of variant thereof in the sample comprises an antibody having specific binding affinity for an epitope of the cardiac troponin marker of variant thereof. 
     
     
         19 . The device of  claim 18 , wherein said means for determining the amount of the cardiac troponin marker of variant thereof in the sample further comprises a second antibody having specific binding affinity for a second epitope of the cardiac troponing marker or variant thereof. 
     
     
         20 . The device of  claim 19 , wherein the epitope of the cardiac troponin marker or variant thereof consists of amino acids 125-131 and the second epitope of the cardiac troponin marker or variant thereof consists of amino acids 136-147.