Lipid biomarkers for stable and unstable heart disease

Abstract

The present invention relates generally to the field of diagnostic and prognostic assays for heart disease. More particular, the present invention provides an assay for diagnosing the presence or extent of development of heart disease or its classification or state thereof. The assay of the present invention is also useful in the stratification of a subject with respect to a risk of developing heart disease. The assay of the present invention is also capable of integration into pathology architecture to provide a diagnostic and reporting system.

1 . A method to stratify a subject as vulnerable or non-vulnerable to plaque rupture, the method comprising determining the levels of at least two lipid analytes in a biological sample from the subject that comprises lipids, wherein the at least two lipid analytes are selected from the group consisting of: CE 14:0, CE 15:0, CE16:2, CE 16:1, CE 16:0, CE 17:1, CE 17:0, CE 18:3, CE 18:2, CE 18:1, CE18:0, CE 20:5, CE 20:4, CE 20:3, CE 20:2, CE 20:1, CE 22:6, CE 22:5, CE 22:4, CE 22:3, CE 22:2, CE 22:1, CE 22:0, CE 24:6, CE 24:5, CE24:4, CE 24:3, CE 24:2, CE 24:1, and CE 24:0; wherein the level of the at least two lipid analytes is different between vulnerable subjects and non-vulnerable subjects and wherein the level of the at least two lipid analytes in the subject relative to a control identifies the subject as being vulnerable or non-vulnerable to plaque rupture. 
     
     
         2 . The method of  claim 1 , comprising comparing the level of the at least two lipid analytes in the subject to the respective levels of the same lipid analytes in at least one control subject selected from a vulnerable subject and a non-vulnerable subject, wherein a similarity in the respective levels of the at least two lipid analytes between the subject and the non-vulnerable subject identifies the subject as being non-vulnerable, and wherein a similarity in the respective levels of the at least two lipid analytes between the subject and the vulnerable subject identifies the subject as being vulnerable to plaque rupture. 
     
     
         3 . The method of  claim 2 , further comprising comparing the level of the at least two lipid analytes in the subject to the respective levels of the same lipid analytes in at least one normal subject, wherein a similarity in the respective levels of the at least two lipid analytes between the subject and the normal subject identifies the subject as being normal with respect to plaque rupture. 
     
     
         4 . The method of  claim 1 , comprising determining or determining and comparing the levels of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16 of the at least two lipid analytes. 
     
     
         5 - 12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein the levels of lipid analytes are used in combination with one or more traditional risk factors selected from age, sex, smoker, diabetes, hypertension, CAD family history, BMI, total cholesterol, LDL, HDL, triglycerides, glucose and hsCRP to thereby identify the subject as being vulnerable or non-vulnerable to plaque rupture. 
     
     
         14 . A method to stratify a subject with respect to heart disease, the method comprising determining the levels of at least two lipid analytes in a biological sample from the subject that comprises lipids, wherein the at least two lipid analytes are selected from the group consisting of: CE 14:0, CE 15:0, CE16:2, CE 16:1, CE 16:0, CE 17:1, CE 17:0, CE 18:3, CE 18:2, CE 18:1, CE18:0, CE 20:5, CE 20:4, CE 20:3, CE 20:2, CE 20:1, CE 22:6, CE 22:5, CE 22:4, CE 22:3, CE 22:2, CE 22:1, CE 22:0, CE 24:6, CE 24:5, CE24:4, CE 24:3, CE 24:2, CE 24:1, and CE 24:0; wherein the level of the at least two lipid analytes is different between normal and heart disease subjects and wherein the level of the at least two lipid analytes in the subject relative to a control provides an indication of the presence or absence of heart disease. 
     
     
         15 . The method of  claim 14 , comprising comparing the level of the at least two lipid analytes in the subject to the respective levels of the same lipid analytes in at least one control subject selected from a normal subject and a heart disease subject, wherein a similarity in the respective levels of the at least two lipid analytes between the subject and the heart disease subject identifies the subject having heart disease, and wherein a similarity in the respective levels of the at least two lipid analytes between the subject and the normal subject identifies the subject as a normal subject with respect to heart disease. 
     
     
         16 . The method of  claim 14 , comprising determining or determining and comparing the levels of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16 of the at least two lipid analytes. 
     
     
         17 - 21 . (canceled) 
     
     
         22 . The method of  claim 14 , wherein the levels of the at least two lipid analytes are used in combination with one or more traditional risk factors selected from age, sex, smoker, diabetes, hypertension, CAD family history, BMI, total cholesterol, LDL, HDL, triglycerides, glucose and hsCRP to thereby identify the subject as being normal or having heart disease. 
     
     
         23 . The method of  claim 1 , wherein the step of determining the levels of at least two lipid analytes is done using mass spectrometry. 
     
     
         24 . The method of  claim 14 , wherein the step of determining the levels of at least two lipid analytes is done using mass spectrometry. 
     
     
         25 . The method of  claim 23 , wherein the mass spectrometry is electrospray ionization-tandem mass spectrometry. 
     
     
         26 . The method of  claim 24 , wherein the mass spectrometry is electrospray ionization-tandem mass spectrometry. 
     
     
         27 . The method of  claim 1 , wherein the biological sample comprises blood, serum, or plasma. 
     
     
         28 . The method of  claim 14 , wherein the biological sample comprises blood, serum, or plasma. 
     
     
         29 . The method of  claim 1 , further comprising providing therapeutic and/or behavioral modification to the subject based on whether the subject is determined to be vulnerable or non-vulnerable to plaque rupture. 
     
     
         30 . The method of  claim 14 , further comprising providing therapeutic and/or behavioral modification to the subject based on whether the determining step indicates the presence or absence of heart disease.