Fatty acid pattern analysis for predicting acute coronary syndrome

Abstract

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

What is claimed is: 
     
         1 . A method for predicting the risk of acute coronary syndrome (ACS) in a human subject, comprising:
 (a) measuring a combination of fatty acid markers in 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 FRS model alone, the combination of the fatty acid markers comprising at least the following fatty acids: linoleic acid, gamma-linolenic acid, and docosahexaenoic acid (DHA);   (b) comparing the amount of the fatty acid markers measured in the fatty acid sample to a control; and   (c) predicting a risk of ACS based on the comparing in step (b), wherein the difference between the measured fatty acid markers and the control exceeding a statistical significance indicates a risk of ACS.   
     
     
         2 . The method of  claim 1 , further comprising, prior to the measuring step:
 identifying the combination of the fatty acid markers from a blood component of a human subject, wherein the combination of the fatty acid markers discriminates the ACS cases from controls better than the Framingham risk score (FRS) model.   
     
     
         3 . The method of  claim 1 , wherein the combination of the fatty acid markers comprises linoleic acid, gamma-linolenic acid, DHA, and eicosapentaenoic acid (EPA). 
     
     
         4 . The method of  claim 1 , wherein the combination of the fatty acid markers further comprises one or more fatty acid selected from the group consisting of stearic acid, alpha-linoleic acid, palmitoleic acid, arachidonic acid, trans-palmitoleic acid, eicosadienoic acid, and trans-oleic acid. 
     
     
         5 . The method of  claim 1 , wherein the combination of the fatty acid markers comprises linoleic acid, gamma-linolenic acid, DHA, stearic acid, alpha-linoleic acid, palmitoleic acid, arachidonic acid, and trans-palmitoleic acid. 
     
     
         6 . The method of  claim 1 , wherein the combination of the fatty acid markers comprises linoleic acid, gamma-linolenic acid, DHA, stearic acid, alpha-linoleic acid, palmitoleic acid, arachidonic acid, trans-palmitoleic acid, eicosadienoic acid, and trans-oleic acid. 
     
     
         7 . The method of  claim 1 , 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, eicosadienoic acid, eicosatrienoic acid, arachidonic acid, n-6 docosapentaenoic acid, docosatetraenoic acid, alpha-linolenic acid, eicosapentaenoic acid, and n-3 docosapentaenoic acid. 
     
     
         8 . The method of  claim 1 , wherein the combination of the fatty acid markers comprises palmitic acid, stearic acid, palmitoleic acid, oleic acid, trans palmitoleic acid, trans oleic acid, trans, trans linoleic acid, linoleic acid, gamma-linolenic acid, eicosadienoic acid, eicosatrienoic acid, arachidonic acid, n-6 docosapentaenoic acid, docosatetraenoic acid, alpha-linolenic acid, eicosapentaenoic acid, n-3 docosapentaenoic acid, eicosapentaenoic acid, and docosahexaenoic acid. 
     
     
         9 . The method of  claim 1 , wherein the combination of the fatty acid markers comprises palmitic acid, oleic acid, trans palmitoleic acid, trans oleic acid, linoleic acid, gamma-linolenic acid, n-6 docosapentaenoic acid, docosatetraenoic acid, alpha-linolenic acid, eicosapentaenoic acid, n-3 docosapentaenoic acid, eicosapentaenoic acid, and docosahexaenoic acid. 
     
     
         10 . The method of  claim 1 , 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. 
     
     
         11 . The method of  claim 10 , 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.   
     
     
         12 . The method of  claim 10 , 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. 
     
     
         13 . The method of  claim 1 , further comprising:
 determining a Framingham risk score (FRS) for the subject based on one or more FRS risk factors; and   including the ACS risk predicting step c) into the FRS model to modify the Framingham risk score, wherein the modified Framingham risk score is used to correlate with ACS in the human subject.   
     
     
         14 . The method of  claim 1 , 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. 
     
     
         15 . The method of  claim 1 , wherein the blood component is red blood cells. 
     
     
         16 . The method of  claim 1 , wherein the subject has a family history of ACS, a genetic predisposition to ACS, and/or has previously suffered from ACS. 
     
     
         17 . The method of  claim 1 , wherein the acute coronary syndrome is myocardial infarction or unstable angina. 
     
     
         18 . The method of  claim 1 , further comprising
 determining an ACS risk score for the subject based on one or more standard coronary heart disease (CHD) risk factors, wherein the CHD risk factors are selected from the group consisting of age, sex, total cholesterol (or LDL cholesterol), HDL-cholesterol, diabetes, smoking status and blood pressure; and   including the ACS risk predicting step c) into the ACS risk score to modify the ACS risk score, wherein the modified ACS risk score is used to correlate with ACS in the human subject.   
     
     
         19 . A method for predicting the risk of acute coronary syndrome (ACS) in a human subject, comprising:
 (a) measuring a combination of fatty acid markers in 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 FRS model alone, the combination of the fatty acid markers comprising three or more of the following fatty acids: linoleic acid, gamma-linolenic acid, docosahexaenoic acid, eicosapentaenoic acid, oleic acid, alpha-linolenic acid, n-3 docosapentaenoic acid, palmitic acid, stearic acid, elaidic acid, n-6 docosapentaenoic acid, docosatetraenoic acid, palmitoleic acid, arachidonic acid, and cis-11,14-eicosadienoic acid;   (b) comparing the amount of fatty acid markers measured in the fatty acid sample to a control; and   (c) predicting a risk of ACS based on the comparing in step (b), wherein the difference between the measured fatty acid markers and the control exceeding a statistical significance indicates a risk of ACS.   
     
     
         20 . The method of  claim 19 , wherein the combination of the fatty acid markers comprises at least five of the fatty acid markers. 
     
     
         21 . The method of  claim 19 , further comprising, prior to the measuring step: identifying the combination of the fatty acid markers from a blood component of a human subject, wherein the combination of the fatty acid markers discriminates the ACS cases from controls better than the FRS model. 
     
     
         22 . A method for predicting the risk of acute coronary syndrome (ACS) in a human subject, comprising:
 (a) measuring a combination of fatty acid markers in 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 FRS model alone, the combination of the fatty acid markers comprising at least the following fatty acids: linoleic acid, alpha-linolenic acid, arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA);   (b) comparing the amount of fatty acid markers measured in the fatty acid sample to a control; and   (c) predicting a risk of ACS based on the comparing in step (b), wherein the difference between the measured fatty acid markers and the control exceeding a statistical significance indicates a risk of ACS.   
     
     
         23 . The method of  claim 22 , further comprising, prior to the measuring step:
 identifying the combination of the fatty acid markers from a blood component of a human subject, wherein the combination of the fatty acid markers discriminates the ACS cases from controls better than the FRS model.