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 heart failure, 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, wherein the subject is undergoing exercise therapy at the second time point;   (c) identifying a subject having an elevated second level of soluble ST2 compared to the first level of soluble ST2 and treating the subject with a treatment of heart failure that does not include exercise therapy.   
     
     
         2 . The method of  claim 1 , 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 comprise blood, plasma, or serum. 
     
     
         3 . The method of  claim 1 , wherein the subject is hypercholesterolemic, hypertriglyceridemic, hyperlidemic, a smoker, hypertensive, or has a body mass index of greater than 30. 
     
     
         4 . The method of  claim 1 , wherein the method further comprises determining a level of cardiac troponin, B type natriuretic peptide, atrial natriuretic peptide, or C-reactive protein in the biological sample obtained from the subject at the first time point and in the biological sample obtained from the subject at the second time point. 
     
     
         5 . The method of  claim 1 , wherein the subject is previously diagnosed as having heart failure. 
     
     
         6 . The method of  claim 1 , wherein the first level of soluble ST2 and the second level of soluble ST2 are determined using an antibody or an antibody fragment thereof that binds to soluble ST2. 
     
     
         7 . The method of  claim 1 , wherein the subject in step (a) is already undergoing exercise therapy. 
     
     
         8 . The method of  claim 1 , wherein the subject is treated with exercise therapy after the first time point and before the second time point. 
     
     
         9 . The method of  claim 1 , wherein the treatment of heart failure that does not include exercise therapy comprises 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. 
     
     
         10 . The method of  claim 9 , 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. 
     
     
         11 . The method of  claim 9 , wherein the lipid-reducing agent is a statin. 
     
     
         12 . A method of treating a subject having heart failure, 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, wherein the subject is undergoing exercise therapy at the second time point;   (c) identifying a subject having an decreased second level of soluble ST2 compared to the first level of soluble ST2 and continuing to treat the subject with exercise therapy.   
     
     
         13 . 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 comprise blood, plasma, or serum. 
     
     
         14 . The method of  claim 12 , wherein the subject is hypercholesterolemic, hypertriglyceridemic, hyperlidemic, a smoker, hypertensive, or has a body mass index of greater than 30. 
     
     
         15 . The method of  claim 12 , wherein the method further comprises determining a level of cardiac troponin, B type natriuretic peptide, atrial natriuretic peptide, or C-reactive protein in the biological sample obtained from the subject at the first time point and in the biological sample obtained from the subject at the second time point. 
     
     
         16 . The method of  claim 12 , wherein the subject is previously diagnosed as having heart failure. 
     
     
         17 . The method of  claim 12 , wherein the first level of soluble ST2 and the second level of soluble ST2 are determined using an antibody or an antibody fragment thereof that binds to soluble ST2. 
     
     
         18 . The method of  claim 12 , wherein the subject in step (a) is already undergoing exercise therapy. 
     
     
         19 . The method of  claim 12 , wherein the subject is treated with exercise therapy after the first time point and before the second time point. 
     
     
         20 . The method of  claim 12 , wherein the treatment of heart failure that does not include exercise therapy comprises 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. 
     
     
         21 . The method of  claim 20 , 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. 
     
     
         22 . The method of  claim 20 , wherein the lipid-reducing agent is a statin.