Soluble CD40L (CD 154) as a prognostic marker of atherosclerotic diseases

Abstract

This invention involves the new use of a diagnostic test to determine the risk of atherosclerotic diseases such as myocardial infarction and stroke, particularly among individuals with no signs or symptoms of current disease and among nonsmokers. Further, this invention involves the new use of a diagnostic test to assist physicians in determining which individuals at risk will preferentially benefit from certain treatments designed either to prevent first or recurrent myocardial infarctions and strokes, or to treat acute and chronic cardiovascular disorders. Methods for treatment are also described.

1 .- 11 . (canceled)  
     
     
         12 . A method for characterizing an individual's risk profile of developing a future cardiovascular disorder associated with atherosclerotic disease, comprising: 
 obtaining a level of sCD40L in the individual,    comparing the sCD40L level to a first predetermined value to establish a first risk value,    obtaining a level of a cholesterol or C-Reactive Protein (CRP) in the individual,    comparing the level of the cholesterol or C-Reactive Protein (CRP) to a second predetermined value to establish a second risk value, and    characterizing the individual's risk profile of developing the cardiovascular disorder based upon the combination of the first risk value and the second risk value, wherein the combination of the first risk value and second risk value establishes a third risk value different from said first and second risk values.    
     
     
         13 . The method of  claim 12 , wherein said individual is an apparently healthy, non-smoking individual.  
     
     
         14 .- 17 . (canceled)  
     
     
         18 . The method of  claim 12 , wherein the cardiovascular disorder is stroke.  
     
     
         19 . The method of  claim 12 , wherein the cardiovascular disorder is nonfatal myocardial infarction.  
     
     
         20 . (canceled)  
     
     
         21 . A method for evaluating the likelihood that an individual will benefit from treatment with an agent for reducing the risk of a cardiovascular disorder associated with atherosclerotic disease, the agent selected from the group consisting of anti-inflammatory agents, anti-thrombotic agents, anti-platelet agents, fibrinolytic agents, lipid reducing agents, direct thrombin inhibitors, and glycoprotein II b/IIIa receptor inhibitors comprising: 
 obtaining a level of sCD40L in the individual, and    comparing the level of sCD40L to a predetermined value, wherein the level of sCD40L in comparison to the predetermined value is indicative of whether the individual will benefit from treatment with said agents, and    characterizing whether the individual is likely to benefit from said treatment based upon said comparison.    
     
     
         22 . (canceled)  
     
     
         23 . The method of  claim 21 , wherein said individual is an apparently healthy; non-smoking individual.  
     
     
         24 .- 27 . (canceled)  
     
     
         28 . The method of  claim 21 , wherein the cardiovascular disorder is stroke.  
     
     
         29 . The method of  claim 21 , wherein the cardiovascular disorder is myocardial infarction.  
     
     
         30 . A method for treating a subject to reduce the risk of a cardiovascular disorder, comprising: 
 selecting and administering to a subject who is known to have an above-normal level of sCD40L an agent for reducing the risk of the cardiovascular disorder in an amount effective to lower the risk of the subject developing a future cardiovascular disorder, wherein the agent is an anti-inflammatory agent, an antithrombotic agent, an anti-platelet agent, a fibrinolytic agent, a lipid reducing agent, a direct thrombin inhibitor, a glycoprotein IIb/IIIa receptor inhibitor, an agent that binds to cellular adhesion molecules and inhibits the ability of white blood cells to attach to such molecules, a calcium channel blocker, a beta-adrenergic receptor blocker, a cyclooxygenase-2 inhibitor, or an angiotensin system inhibitor.    
     
     
         31 . The method of  claim 30 , wherein the subject is otherwise free of symptoms calling for treatment with the agent.  
     
     
         32 . The method of  claim 30 , wherein the subject is apparently healthy and the subject does not have an elevated risk of an adverse cardiovascular event.  
     
     
         33 . The method of  claim 30 , wherein the subject is nonhyperlipidemic.  
     
     
         34 . The method of  claim 30 , wherein the agent is a non-aspirin, anti-inflammatory agent.  
     
     
         35 .- 38 . (canceled)  
     
     
         39 . The method of  claim 30 , wherein the agent is a lipid reducing agent.  
     
     
         40 . The method of  claim 39 , wherein the lipid reducing agent is gemfibrozil, cholystyramine, colestipol, nicotinic acid, probucol lovastatin, fluvastatin, simvastatin, atorvastatin, pravastatin, or cerivastatin.  
     
     
         41 .- 70 . (canceled)  
     
     
         71 . A method for reducing sCD40L levels in a subject to lower the risk of an adverse cardiovascular disorder, comprising: 
 selecting and administering to a subject having elevated levels of sCD40L an agent that reduces sCD40L levels in an amount effective to reduce the sCD40L levels in the subject.    
     
     
         72 . The method of  claim 71 , wherein the agent is a lipid lowering agent.  
     
     
         73 . The method of  claim 71 , wherein the subject is apparently healthy.  
     
     
         74 . The method of  claim 71 , wherein the subject is not otherwise at an elevated risk of having an adverse cardiovascular event.  
     
     
         75 . The method of  claim 71 , wherein the subject has elevated C-Reactive Protein (CRP) levels.  
     
     
         76 . The method of  claim 71 , wherein the subject is otherwise free of indications calling for treatment with a lipid reducing agent.