Fatty acid pattern analysis for predicting acute coranary syndrome

Abstract

The present invention provides blood based methods for predicting risk of acute coronary syndrome in a subject.

1 - 23 . (canceled) 
     
     
         24 . A method for predicting the risk of acute coronary syndrome (ACS) in a human subject, comprising:
 (a) selecting a combination of fatty acid markers from a fatty acid sample isolated from a blood component of a human subject, wherein the combination of the fatty acid markers, alone or together with the Framingham risk score (FRS) model, discriminates the ACS cases from controls better than the Framingham risk score (FRS) model as assessed by having a greater c-statistic value, the combination of the fatty acid markers comprising at least the following fatty acids: linoleic acid, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA);   (b) measuring the combination of the fatty acid markers in a fatty acid sample isolated from a blood component of a human subject;   (c) comparing the amount of the fatty acid markers measured in the fatty acid sample to a control; and   (d) predicting a risk of ACS based on the comparing in step (c), wherein the difference between the measured fatty acid markers and the control exceeding a statistical significance indicates a risk of ACS.   
     
     
         25 . The method of  claim 24 , wherein the combination of the fatty acid markers further comprises docosapentaenoic acid (DPA), arachidonic acid, or combinations thereof. 
     
     
         26 . The method of  claim 25 , wherein the docosapentaenoic acid is n-6 docosapentaenoic acid, n-6 docosapentaenoic acid, or combinations thereof. 
     
     
         27 . The method of  claim 24 , wherein the combination of the fatty acid markers further comprises one or more fatty acid selected from the group consisting of palmitic acid, stearic acid, palmitoleic acid, oleic acid, trans palmitoleic, trans oleic acid, trans, trans linoleic acid, gamma-linolenic acid, eicosadienoic acid, eicosatrienoic acid, arachidonic acid, n-6 docosapentaenoic acid, docosatetraenoic acid, alpha-linolenic acid, and n-3 docosapentaenoic acid. 
     
     
         28 . The method of  claim 24 , wherein the measuring step comprises measuring a percent total of each of the fatty acid markers in the fatty acid sample as a percent of total fatty acids in the fatty acid sample. 
     
     
         29 . The method of  claim 28 , wherein the comparing step comprises:
 multiplying the percent total of each of the fatty acid markers in the fatty acid sample by a predetermined weighting coefficient to produce an individual fatty acid score for each of the fatty acid markers; and   summing the individual fatty acid scores to produce a risk score, wherein the risk score is used to correlate with ACS in the human subject.   
     
     
         30 . The method of  claim 28 , further comprising subjecting the percent total of the fatty acid markers in the fatty acid sample to an analysis selected from the group consisting of generalized models, multivariate analysis, and time-to-event survival analysis, to produce a risk score; wherein the risk score is used to correlate with ACS in the human subject. 
     
     
         31 . The method of  claim 24 , further comprising:
 determining a Framingham risk score (FRS) for the subject based on including one or more FRS risk factors in the FRS model calculation; and   modifying the Framingham risk score by combining the ACS risk predicting step (d) into the FRS model, wherein the modified Framingham risk score is used to correlate with ACS in the human subject.   
     
     
         32 . The method of  claim 31 , wherein the FRS risk factors are age, sex, total cholesterol (or LDL cholesterol), HDL-cholesterol, diabetes, smoking status, or blood pressure. 
     
     
         33 . The method of  claim 24 , wherein the blood component is selected from the group consisting of red blood cells, whole blood, serum, platelets, white blood cells, plasma, cholesterol esters, triglycerides, free fatty acids, and plasma phospholipids. 
     
     
         34 . The method of  claim 24 , wherein the blood component is red blood cells. 
     
     
         35 . The method of  claim 24 , wherein the subject has a family history of ACS, a genetic predisposition to ACS, and/or has previously suffered from ACS. 
     
     
         36 . The method of  claim 24 , wherein the acute coronary syndrome is myocardial infarction or unstable angina. 
     
     
         37 . A method for predicting the risk of acute coronary syndrome (ACS) in a human subject, comprising:
 (a) treating a fatty acid sample isolated from a blood component of a human subject with a methylation reagent to produce fatty acid methyl esters (FAMES);   (b) selecting a combination of FAMES markers, wherein the combination of the FAMES markers, alone or together with the Framingham risk score (FRS) model, discriminates the ACS cases from controls better than the Framingham risk score (FRS) model as assessed by having a greater c-statistic value, the combination of the FAMES markers comprising at least the FAMES produced from following fatty acids: linoleic acid, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA);   (c) measuring the combination of the FAMES markers from the fatty acid sample;   (d) comparing the amount of the FAMES markers measured from the fatty acid sample to a control; and   (e) predicting a risk of ACS based on the comparing in step (d), wherein the difference between the measured FAMES markers and the control exceeding a statistical significance indicates a risk of ACS.   
     
     
         38 . The method of  claim 37 , wherein the fatty acids of step (b) further comprises docosapentaenoic acid (DPA), arachidonic acid, or combinations thereof. 
     
     
         39 . The method of  claim 37 , wherein the methylating reagent is a boron-trifluoride methanol solution. 
     
     
         40 . The method of  claim 37 , wherein the FAMES are extracted from the fatty acid sample using a hexane solvent. 
     
     
         41 . A method for predicting the risk of acute coronary syndrome (ACS) in a human subject and treating the human subject having a risk of ACS, comprising:
 (a) selecting a combination of fatty acid markers from a fatty acid sample isolated from a blood component of a human subject, wherein the combination of the fatty acid markers, alone or together with the Framingham risk score (FRS) model, discriminates the ACS cases from controls better than the Framingham risk score (FRS) model as assessed by having a greater c-statistic value, the combination of the fatty acid markers comprising at least the following fatty acids: linoleic acid, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA);   (b) measuring the combination of the fatty acid markers in a fatty acid sample isolated from a blood component of a human subject;   (c) comparing the amount of the fatty acid markers measured in the fatty acid sample to a control;   (d) predicting a risk of ACS based on the comparing in step (c), wherein the difference between the measured fatty acid markers and the control exceeding a statistical significance indicates a risk of ACS; and   (e) treating the human subject predicted to have a risk of ACS by altering the human subject's diet to reduce the risk of ACS.   
     
     
         42 . The method of  claim 41 , wherein the combination of the fatty acid markers further comprises docosapentaenoic acid (DPA), arachidonic acid, or combinations thereof. 
     
     
         43 . The method of  claim 41 , wherein the human subject's diet is altered by adding fish or fish-oil supplements.