Methods of Treating Cardiovascular Diseases and Predicting the Efficacy of Exercise Therapy

Abstract

Methods of treating a subject having a cardiovascular disease, selecting a therapy for a subject having a cardiovascular disease, identifying a subject having a cardiovascular disease that will benefit or not benefit from exercise therapy, determining whether a subject having a cardiovascular disease should begin, continue, not begin, discontinue, or avoid exercise therapy, determining whether a subject having a cardiovascular disease should continue, discontinue, or avoid exercise therapy, reducing the risk of an adverse outcome (e.g., death) in a subject having a cardiovascular disease, and predicting the efficacy of exercise therapy in a subject having a cardiovascular disease. These methods include determining a level of soluble ST2 in a subject.

What is claimed is: 
     
         1 . A method of treating a subject having a cardiovascular disease, the method comprising:
 a) determining a level of soluble ST2 in a biological sample from the subject;   b) identifying a subject that has a decreased level of soluble ST2 in the biological sample compared to a risk or efficacy reference level of soluble ST2; and   c) selecting the identified subject for exercise therapy.   
     
     
         2 . A method of treating a subject having a cardiovascular disease, the method comprising:
 a) determining a level of soluble ST2 in a biological sample from the subject;   b) identifying a subject that has an elevated level of soluble ST2 in the biological sample compared to a risk or efficacy reference level of soluble ST2; and   c) instructing the identified subject not to begin, to discontinue, or to avoid exercise therapy.   
     
     
         3 . A method of selecting a therapy for a subject having a cardiovascular disease, the method comprising:
 a) determining a level of soluble ST2 in a biological sample from the subject, and   b) comparing the level of soluble ST2 in the biological sample to a risk or efficacy reference level of soluble ST2,   wherein a decreased level of soluble ST2 in the biological sample compared to the risk or efficacy reference level indicates that the subject should begin or continue exercise therapy, and an elevated level of soluble ST2 in the biological sample compared to the risk or efficacy reference level indicates that the subject should not begin or should discontinue exercise therapy.   
     
     
         4 . A method of identifying a subject having a cardiovascular disease that will benefit from exercise therapy, the method comprising:
 a) determining a level of soluble ST2 in a biological sample from the subject, and   b) selecting a subject that has a decreased level of soluble ST2 in the biological sample compared to an efficacy reference level of soluble ST2,   wherein the selected subject is identified as a subject that will benefit from exercise therapy.   
     
     
         5 . A method of identifying a subject having a cardiovascular disease that will not benefit from exercise therapy, the method comprising:
 a) determining a level of soluble ST2 in a biological sample from the subject, and   b) selecting a subject that has an elevated level of soluble ST2 in the biological sample compared to an efficacy reference level of soluble ST2,   wherein the selected subject is identified as a subject that will not benefit from exercise therapy.   
     
     
         6 . A method of determining whether a subject having a cardiovascular disease should begin, continue, not begin, or discontinue exercise therapy, the method comprising determining a level of soluble ST2 in a biological sample from the subject, wherein a decreased level of soluble ST2 in the biological sample compared to a risk or efficacy reference level of soluble ST2 indicates that the subject should begin or continue exercise therapy, and an elevated level of soluble ST2 in the biological sample compared to a risk or efficacy reference level of soluble ST2 indicates that the subject should not begin or discontinue exercise therapy. 
     
     
         7 . A method of determining whether a subject having a cardiovascular disease should discontinue or continue exercise therapy, the method comprising:
 a) determining a level of soluble ST2 in a biological sample from the subject at a first time point before or after the start of exercise therapy; and   b) determining a level of soluble ST2 in a biological sample from the subject undergoing exercise therapy at a second time point after the start of exercise therapy and after the first time point,   wherein an elevation in the level of soluble ST2 in the biological sample at the second time point compared to the level of soluble ST2 in the biological sample at the first time point indicates that the subject should discontinue exercise therapy, and a decrease in the level of soluble ST2 in the biological sample at the second time point compared to the level of soluble ST2 in the biological sample at the first time point indicates that the subject should continue exercise therapy.   
     
     
         8 . A method of reducing the risk of an adverse outcome in a subject having a cardiovascular disease, the method comprising:
 a) determining a level of soluble ST2 in a biological sample from the subject;   b) identifying a subject that has a decreased level of soluble ST2 in the biological sample compared to a risk reference level of soluble ST2; and   c) selecting the identified subject for exercise therapy.   
     
     
         9 . A method of reducing the risk of an adverse outcome in a subject having a cardiovascular disease, the method comprising:
 a) determining a level of soluble ST2 in a biological sample from the subject;   b) identifying a subject that has an elevated level of soluble ST2 in the biological sample compared to a risk reference level of soluble ST2; and   c) instructing the identified subject not to begin or to discontinue exercise therapy.   
     
     
         10 . The method of  claim 8  or  9 , where the risk of an adverse outcome is risk of death. 
     
     
         11 . A method of predicting the efficacy of exercise therapy in a subject having a cardiovascular disease, the method comprising:
 a) determining a level of soluble ST2 in a biological sample from the subject; and   b) comparing the level of soluble ST2 in the biological sample to an efficacy reference level of soluble ST2,   wherein a decreased level of soluble ST2 in the biological sample compared to the efficacy reference level of soluble ST2 indicates that exercise therapy will be effective in the subject, and an elevated level of soluble ST2 in the biological sample compared to the efficacy reference level of soluble ST2 indicates that the exercise therapy will not be effective in the subject.   
     
     
         12 . The method of any one of  claims 1 - 9  and  11 , wherein the biological sample comprises blood or serum. 
     
     
         13 . The method of any one of  claims 1 - 9  and  11 , wherein the determining is performed using an antibody or an antibody fragment therof that binds to soluble ST2. 
     
     
         14 . The method of any one of  claims 1 - 9  and  11 , wherein the risk or efficacy reference level of soluble ST2 is a predetermined threshold value. 
     
     
         15 . The method of any one of  claims 1 - 9  and  11 , wherein the reference level is a risk reference level 
     
     
         16 . The method of  claim 15 , wherein the reference level is a risk reference level of soluble ST2 in a subject who experienced or was more likely to experience an adverse outcome and engaged in exercise, a level in a population of subjects who experienced or were more likely to experience an adverse outcome and engaged in exercise, or a threshold level of soluble ST2 above which the risk of an adverse outcome is increased in those who engage in exercise therapy. 
     
     
         17 . The method of any one of  claims 1 - 9  and  11 , wherein the reference level is an efficacy reference level. 
     
     
         18 . The method of  claim 17 , wherein the efficacy reference level of soluble ST2 is a level in a subject who experienced a therapeutic benefit from exercise therapy, a level in a population of subjects who experienced a therapeutic benefit from exercise therapy, or a threshold level of soluble ST2 below which the subject is likely to experience a therapeutic benefit from exercise therapy. 
     
     
         19 . The method of any one of  claims 1 - 9  and  11 , wherein the subject is hypercholesterolemic, hypertriglyceridemic, hyperlidemic, a smoker, hypertensive, or has a body mass index of greater than 30. 
     
     
         20 . The method of any one of  claims 1 - 6 ,  8 ,  9 , and  11 , further comprising determining a level of cardiac troponin I, B-type natriuretic peptide, atrial natriuretic peptide, or C-reactive protein in the biological sample. 
     
     
         21 . The method of  claim 7 , further comprising determining a level of cardiac troponin I, B type natriuretic peptide, atrial natriuretic peptide, or C-reactive protein in the biological sample at the first time point or the biological sample at the second time point. 
     
     
         22 . The method of any one of  claims 1 - 9  and  11 , wherein the cardiovascular disease is selected from the group consisting of: cardiac hypertrophy, myocardial infarction, stroke, arteriosclerosis, and heart failure. 
     
     
         23 . The method of any one of  claims 1 - 9  and  11 , wherein the subject is administered at least one therapeutic agent selected from the group consisting of: anti-inflammatory agents, anti-thrombotic agents, anti-coagulants, anti-platelet agents, lipid-reducing agents, direct thrombin inhibitors, glycoprotein IIb/IIIb receptor inhibitors, calcium channel blockers, beta-adrenergic receptor blockers, cyclooxygenase-2 inhibitors, and renin-angiotensin-aldosterone system (RAAS) inhibitors. 
     
     
         24 . The method of  claim 23 , wherein the RAAS inhibitor is selected from the group consisting of: an angiotensin-converting enzyme inhibitor, an angiotensin II receptor blocker, and an aldosterone antagonist. 
     
     
         25 . The method of  claim 23 , wherein the lipid-reducing agent is a statin.