Biomarker for coronary artery disease

Abstract

In various embodiments methods are provided for identifying a mammal having an elevated risk for an adverse cardiac event (e.g. an MI) and/or determining the prognosis for the mammal. In certain embodiments the methods comprise determining, or causing to be determined, the presence and/or level of antibodies that bind a malondialdehyde-acetaldehyde adduct (MAA adduct) in a biological sample from the mammal, where an elevated level of anti-MAA adduct antibodies, as compared to the level found in a normal healthy mammal is an indicator that that said mammal has one or more atherosclerotic lesions and/or is at elevated risk for a myocardial infarction.

1 : A method of identifying a mammal having an elevated risk for an adverse cardiac event and/or determining the prognosis for said mammal, said method comprising:
 determining, or causing to be determined, the presence and/or level of antibodies that bind a malondialdehyde-acetaldehyde adduct (MAA adduct) in a biological sample from said mammal, where an elevated level of said antibodies, as compared to the level found in a normal healthy mammal is an indicator that that said mammal has one or more atherosclerotic lesions.   
     
     
         2 : The method of  claim 1 , wherein said method comprises:
 determining, or causing to be determined, the presence and/or level of IgG antibodies that bind said adduct; and/or   determining, or causing to be determined, the presence and/or level of IgM antibodies that bind said adduct; and/or   determining, or causing to be determined, the presence and/or level of IgA antibodies that bind said adduct.   
     
     
         3 - 4 . (canceled) 
     
     
         5 : The method of  claim 2 , wherein:
 an elevated level of said IgG antibodies and/or said IgM antibodies, as compared to the level(s) found in a normal healthy mammal is an indicator that that said mammal has one or more atherosclerotic plaques and is at risk for cardiac artery disease;   a level of IgA antibodies elevated as compared to that found in a normal healthy mammal is an indicator that that said mammal has stable angina; and   a level of said IgA antibodies comparable to that found in a normal healthy mammal is an indicator that that said mammal has unstable angina and is at significant risk for a myocardial infarction.   
     
     
         6 - 7 . (canceled) 
     
     
         8 : The method of  claim 2 , wherein
 an elevated level of said IgG antibodies and/or said IgM antibodies, as compared to the level(s) found in a normal healthy mammal is found; and/or   a level of IgA antibodies elevated as compared to that found in a normal healthy mammal is found; and   said mammal is treated as a subject having elevated risk for an adverse cardiac event and/or as a subject having a stable angina.   
     
     
         9 . (canceled) 
     
     
         10 : The method of  claim 8 , wherein said mammal is prescribed an additional test and/or said additional tests are performed. 
     
     
         11 . (canceled) 
     
     
         12 : The method of  claim 10 , wherein said additional tests comprise:
 one or more tests selected from the group consisting of blood tests for heart tissue damage or high risk for heart attack, electrocardiogram, stress test, coronary MRI, and coronary angiography; and/or   blood tests include one or more tests selected from the group consisting of troponin I, T-00745, creatine phosphokinase (CPK), LDL, AST, ALT, and myoglobin; and/or   an exercise tolerance test, a nuclear stress test, cardiac MRI stress, and a stress echocardiogram.   
     
     
         13 - 14 . (canceled) 
     
     
         15 : The method of  claim 8 , wherein said mammal is prescribed a treatment and/or treated. 
     
     
         16 . (canceled) 
     
     
         17 : The method of  claim 15 , wherein:
 said mammal is treated with a pharmaceutical selected from the group consisting of a statin, a beta blocker, nitroglycerin or other nitrate, heparin, ACE inhibitor, angiotensin receptor blockers (ARB), aspirin and other anti-platelets, calcium channel blocker, and Ranolazine; and/or   treated with a treatment selected from the group consisting of angioplasty, percutaneous intervention (PCI) including implantation of a stent, and coronary bypass surgery.   
     
     
         18 - 19 . (canceled) 
     
     
         20 : The method of  claim 2 , wherein the anti-MAA adduct IgA antibody levels and/or a diagnosis based, at least in part, on said levels is recorded in a patient medical record, and/or recorded on or in a medic alert article selected from a card, worn article, or radiofrequency identification (RFID) tag; and/or recorded on a non-transient computer readable medium. 
     
     
         21 - 27 . (canceled) 
     
     
         28 : The method of  claim 2 , wherein said biological sample comprise a sample selected from the group consisting of whole blood, a blood fraction, saliva/oral fluid, urine, a tissue biopsy, pleural fluid, pericardial fluid, cerebral spinal fluid, and peritoneal fluid. 
     
     
         29 - 35 . (canceled) 
     
     
         36 : The method of  claim 2 , wherein the level of one or more of the IgG antibody, the IgM antibody, and/or the IgA antibody is measured using an ELISA assay. 
     
     
         37 - 38 . (canceled) 
     
     
         39 : A method of monitoring the progression of atherosclerosis in a mammal, said method comprising:
 determining, or causing to be determined, the presence and/or level of antibodies that bind a malondialdehyde-acetaldehyde adduct (MAA adduct) in a biological sample from said mammal; and   comparing the level(s) of said antibodies to levels that have been measured for said mammal at a previous point in time, wherein:
 an increase in the total level(s) of antibodies that bind said MAA adduct in said biological sample, as compared to the previous determination, is an indicator that atherosclerotic lesions have worsened in said mammal; and 
 a decrease in the total level(s) of antibodies that bind said MAA adduct in said biological sample, as compared to the previous determination, is an indicator that atherosclerotic lesions decreased in said mammal, or the risk of progression has decreased. 
   
     
     
         40 : The method of  claim 39 , wherein said mammal is treated for atherosclerosis during the time between said previous point in time and the time said determining or causing to be determined and:
 an increase in the total level(s) of antibodies that bind said MAA adduct in said biological sample, as compared to the previous determination, is an indicator the treatment has limited or no efficacy and that lesions have worsened in said mammal; and   a decrease in the total level(s) of antibodies that bind said MAA adduct in said biological sample, as compared to the previous determination, is an indicator that the treatment has at least some efficacy and that atherosclerotic lesions have decreased in said mammal, or the risk of progression has decreased.   
     
     
         41 : The method of  claim 39 , wherein:
 said method comprises determining, or causing to be determined, the presence and/or level of IgG antibodies that bind said adduct; and/or   said method comprises determining, or causing to be determined, the presence and/or level of IgM antibodies that bind said adduct; and/or   said method comprises determining, or causing to be determined, the presence and/or level of IgA antibodies that bind said adduct.   
     
     
         42 - 43 . (canceled) 
     
     
         44 : The method of  claim 41 , wherein:
 an increase in the total level(s) of antibodies that bind said MAA adduct in said biological sample and/or a class switching from IgM to IgG and/or IgA antibodies, as compared to the previous determination, is an indicator that atherosclerotic lesions have worsened in said mammal; and   a decrease in the total level(s) of antibodies that bind said MAA adduct in said biological sample and/or a class switching from IgG to IgM antibodies, as compared to the previous determination, is an indicator that atherosclerotic lesions have decreased in said mammal.   
     
     
         45 : The method of  claim 41 , wherein an increase in IgA antibodies, as compared to the previous determination is an indicator that atherosclerotic lesions in said mammal are become more stable, and/or that said treatment is at least partially increasing the stability of atherosclerotic lesions in said mammal. 
     
     
         46 : The method of  claim 39 , wherein said treatment comprises one or more modalities selected from the group consisting of said mammal, a change in diet, an increase in exercise, weight loss, prescription/administration of a statin, prescription/administration of a beta blocker, prescription/administration of a calcium channel blocker, prescription/administration of angiotensin converting enzyme (ACE) inhibitors, cardiac catheterization, stress testing, and vessel stenting. 
     
     
         47 - 61 . (canceled) 
     
     
         62 : A method of treating a mammal, said method comprising:
 receiving measurements of the presence and/or level of antibodies that bind a malondialdehyde-acetaldehyde adduct (MAA adduct) in a biological sample from said mammal, where an elevated level of said antibodies, as compared to the level found in a normal healthy mammal is an indicator that that said mammal has one or more atherosclerotic lesions; and   when said antibodies show an elevated level providing or causing to be provided additional tests relevant to atherosclerosis and/or providing or causing to be provided additional treatments relevant to atherosclerosis to said mammal.   
     
     
         63 : The method of  claim 62 , wherein said method comprises:
 receiving a measurement of the presence and/or level of IgG antibodies that bind said adduct; and/or   receiving a measurement of the presence and/or level of IgM antibodies that bind said adduct; and/or   receiving a measurement of the presence and/or level of IgA antibodies that bind said adduct.   
     
     
         64 - 65 . (canceled) 
     
     
         66 : The method of  claim 62 , wherein:
 a level of said IgA antibodies elevated as compared to that found in a normal healthy mammal is an indicator that that said mammal has stable angina, and said mammal is further tested and/or treated as a subject having or at risk for a stable angina; and   a level of said IgA antibodies comparable to that found in a normal healthy mammal is an indicator that that said mammal has unstable angina and is at significant risk for a myocardial infarction, and said mammal is further tested and/or treated as a subject having or at risk for an unstable angina and and/or a myocardial infarction.   
     
     
         67 - 69 . (canceled) 
     
     
         70 : The method of  claim 66 , wherein said further testing comprises:
 performing one or more tests selected from the group consisting of blood tests for heart tissue damage or high risk for heart attack, electrocardiogram, stress test, coronary MRI, and coronary angiography; and/or   performing blood tests blood tests selected from the group consisting of troponin I, T-00745, creatine phosphokinase (CPK), LDL, AST, ALT, and myoglobin; and/or   performing one or more tests selected from the group consisting of an exercise tolerance test, a nuclear stress test, and a stress echocardiogram.   
     
     
         71 - 74 . (canceled) 
     
     
         75 : The method of  claim 70 , wherein:
 said mammal is administered a pharmaceutical selected from the group consisting of a statin, a beta blocker, nitroglycerin or other nitrate, heparin, ACE inhibitor, angiotensin receptor blockers (ARB), aspirin and other anti-platelets, calcium channel blocker, and Ranolazine; and/or   said mammal is treated with a treatment selected from the group consisting of angioplasty, percutaneous intervention (PCI) including implantation of a stent, and coronary bypass surgery.   
     
     
         76 - 89 . (canceled) 
     
     
         90 : A kit for evaluating the presence and/or prognosis for atherosclerosis in a mammal, said kit comprising packaging containing:
 a MAA protein adduct; and   a first reagent that specifically binds to IgG antibodies bound to said MAA protein adduct and/or a second reagent that specifically binds to IgM antibodies bound to said MAA protein adduct.   
     
     
         91 - 99 . (canceled) 
     
     
         100 : A method of treating a mammal, said method comprising:
 administering to said mammal a composition comprising an antibody that specifically binds a MAA adduct attached to a detectable label or capable of being selectively bound by a detectable label;   detecting said the localization of said label within the mammal's vasculature wherein said localization indicates a potentially unstable plaque.   
     
     
         101 - 103 . (canceled)