Assessing the risk of a major adverse cardiac event in patients with chest pain

Abstract

Methods for characterizing the near terns risk of experiencing a major adverse cardiac event in a patient presenting with chest pain are provided. In one embodiment the method comprises determining the level of myeloperoxidase (MPO) activity in a bodily sample obtained. from the patient. In another embodiment, the method comprises determining the level of MPO mass in a bodily sample obtained from the patient. In another embodiment, the method comprises determining the level of one or more select MPO-generated oxidation products in a bodily sample obtained from the patient. The select MPO-generated oxidation products are dityrosine, nitrotyrosine, chlorotyrosine, methionine sulphoxide or an MPO-generated lipid peroxidation product. Levels of MPO activity, MPO mass, or the select MPO-generated oxidation product in bodily samples from the test subject are then compared to a control value that is derived from measurements of MPO activity, MPO mass, or the select MPO-generated oxidation product in comparable bodily samples obtained from control population. Such comparison can also be used to determine the near term treatment of the patient.

1 - 22 . (canceled) 
     
     
         23 . A system comprising:
 a) a plasma or serum sample from a subject with chest pain;   b) reagents for detecting the level of myeloperoxidase in said plasma or serum sample, wherein said reagents comprise anti-myeloperoxidase (MPO) antibodies; and   c) a table comprising predetermined values for correlating said level of MPO in said plasma or serum sample with the risk of experiencing a major cardiac event within 6 months of presenting with chest pain, wherein at least a portion of said predetermined values define a plurality of CVD risk groups.   
     
     
         24 . The system of  claim 23 , wherein said plasma or serum sample is a plasma sample. 
     
     
         25 . The system of  claim 23 , wherein said plasma or serum sample is a serum sample. 
     
     
         26 . The system of  claim 23 , wherein each of said CVD risk groups is defined by a range of values. 
     
     
         27 . The system of  claim 23 , wherein said plurality of CVD risk groups comprise a high risk group, a medium risk group, and a low risk group. 
     
     
         28 . The system of  claim 23 , wherein said plurality of CVD risk groups comprise a low risk quadrant, second and third mid-range quadrants, and a high risk quadrant. 
     
     
         29 . The system of  claim 23 , wherein said table further comprises C-reactive protein levels. 
     
     
         30 . The system of  claim 23 , wherein said predetermined values in said table were generated from a population of patients with cardiovascular disease. 
     
     
         31 . A method for evaluating the effect of a cardiovascular disease (CVD) therapeutic agent on a subject with chest pain comprising:
 a) determining a first level of MPO mass in a bodily sample taken from a subject with chest pain prior to administration of a CVD therapeutic agent, and   b) determining a second level of MPO mass in a corresponding bodily fluid taken from said subject following administration of said CVD therapeutic agent.   
     
     
         32 . The method of  claim 31 , wherein a decrease in said first level to said second level is indicative of a positive effect of said CVD therapeutic agent on cardiovascular disease in said subject. 
     
     
         33 . The method of  claim 31 , wherein said CVD therapeutic agent comprises a lipid reducing agent. 
     
     
         34 . The method of  claim 31 , wherein said CVD therapeutic agent is selected from the group consisting of: an anti-inflammatory agent, an insulin sensitizing agent, an anti-hypertensive agent, an anti-thrombotic agent, an anti-platelet agent, a fibrinolytic agent, a direct thrombin inhibitor, an ACAT inhibitor, a CDTP inhibitor, and a glycoprotein IIb/IIIa receptor inhibitor. 
     
     
         35 . The method of  claim 31 , wherein said CVD is atherosclerotic CVD. 
     
     
         36 . The method of  claim 31 , wherein said bodily sample is a plasma sample. 
     
     
         37 . The method of  claim 31 , wherein said determining in step a) and/or step b) comprises contacting said bodily sample with an anti-MPO antibody. 
     
     
         38 . The method of  claim 37 , wherein said determining in step a) and/or step b) further comprises spectrophotometrically detecting said anti-MPO antibody. 
     
     
         39 . A method for identifying and analyzing myeloperoxidase (MPO) concentration in a sample comprising:
 a) contacting a sample with an anti-MPO antibody, wherein said sample is a plasma sample from a subject with chest pain;   b) detecting MPO levels in said plasma sample;   c) generating a standard of known MPO levels; and   d) comparing said MPO levels in said sample to said standard to analyze the MPO concentration in said sample.   
     
     
         40 . The method of  claim 39 , wherein the step of detecting MPO levels is performed spectrophotometrically. 
     
     
         41 . The method of  claim 39 , further comprising, prior to step a), centrifuging an anti-coagulated blood sample from said subject to generate said plasma sample. 
     
     
         42 . The method of  claim 39 , further comprising step e) comparing said MPO concentration in said sample from said subject to a control MPO concentration from apparently healthy subjects, and identifying said MPO concentration in said sample from said subject as being elevated compared to said control MPO concentration.