Methods for assessing the risk for development of cardiovascular disease

Abstract

The present invention relates to diagnostic tests, methods and kits that are useful to assess a subject's risk of developing a pathologic condition related in part to the presence of HDL oxidation product. Measuring the quantity of one or more HDL oxidation products present in the blood is useful in evaluating risk for developing or evaluating the se verity of a disease or evaluating response to treatment for such a disease as, for instance, cardiovascular disease

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows: 
     
         1 . A system comprising:
 a) isotope-labeled 3-chlorotyrosine and/or isotope-labeled 3-nitrotyrosine;   b) a gas chromatograph and/or a mass spectrometer; and   c) a treated sample from a subject having, or at risk for, cardiovascular disease, wherein said treated sample: i) comprises isolated HDL, and ii) is depleted in ApoB and ApoE proteins.   
     
     
         2 . The system of  claim 1 , wherein both said isotope-labeled 3-chlorotyrosine and isotope-labeled 3-nitrotyrosine are present. 
     
     
         3 . The system of  claim 1 , wherein both said gas chromatograph and said mass spectrometer are present. 
     
     
         4 . The system of  claim 1 , further comprising isotope-labeled L-tyrosine. 
     
     
         5 . The system of  claim 1 , wherein said biological sample is from a subject having cardiovascular disease. 
     
     
         6 . The system of  claim 1 , wherein said biological sample is from a subject at risk for cardiovascular disease. 
     
     
         7 . A method for assessing the presence of cardiovascular disease wherein abnormal levels of at least one high-density lipoprotein (“HDL”) oxidation product is associated with the presence of cardiovascular disease comprising the steps of:
 a) obtaining a biological sample from a subject; 
 b) measuring by spectrometry the amount of an HDL tyrosine oxidation product in the biological sample, wherein the HDL tyrosine oxidation product is at least one of 3-nitrotyrosine, 3-chlorotyrosine or o′,o′-dityrosine; and 
 c) comparing the amount of the HDL tyrosine oxidation product in the biological sample with a range of predetermined values indicative of a healthy population, wherein an increase in the oxidized HDL tyrosine product as compared to a predetermined normal reference range, is indicative of the presence of cardiovascular disease in the subject. 
 
     
     
         8 . The method of  claim 7 , wherein the HDL tyrosine oxidation product is an apo A-I oxidation product. 
     
     
         9 . The method of  claim 7 , wherein the cardiovascular disease is selected from the group consisting of atherosclerosis, coronary heart disease, ischemic heart disease, myocardial infarction, angina pectoris, peripheral vascular disease, cerebrovascular disease, and stroke. 
     
     
         10 . The method of  claim 7 , wherein the cardiovascular disease is atherosclerosis. 
     
     
         11 . The method of  claim 7 , wherein the cardiovascular disease is associated with renal disease or renal failure. 
     
     
         12 . The method of  claim 7 , wherein the HDL oxidation product is 3-nitrotyrosine. 
     
     
         13 . The method of  claim 7 , wherein the HDL oxidation product is 3-chlorotyrosine. 
     
     
         14 . The method of  claim 7 , wherein the HDL oxidation product is o′,o′-dityrosine. 
     
     
         15 . The method of  claim 7 , wherein the assessing is determining risk for developing cardiovascular disease. 
     
     
         16 . The method of  claim 7 , wherein the assessing is determining response of the cardiovascular disease to a treatment. 
     
     
         17 . The method of  claim 7 , wherein the assessing is quantifying the severity of the cardiovascular disease, 
     
     
         18 . The method of  claim 7 , wherein said one biological sample is selected from the group consisting of whole blood cells, whole blood cell lysates, erythrocytes, white blood cells, plasma, serum, urine, CSF and saliva. 
     
     
         19 . The method of  claim 7 , wherein measuring by spectrometry said HDL oxidation product is performed by mass spectrometry. 
     
     
         20 . The method of  claim 19 , wherein said mass spectrometry is isotope dilution mass spectrometry, 
     
     
         21 . A method for assessing risk for developing cardiovascular disease comprising the steps of:
 a) obtaining a biological sample from a subject;   b) measuring by spectrometry the amount of at least one high-density lipoprotein (“HDL”) tyrosine oxidation product in the biological sample, wherein the HDL tyrosine oxidation product is at least one of 3-nitrotyrosine, 3-chlorotyrosine or o′,o′-dityrosine; and   c) comparing the amount of the HDL tyrosine oxidation product in the biological sample with a range of predetermined values indicative of a healthy population wherein an increase in the oxidized HDL tyrosine product as compared to a predetermined normal reference range is indicative of an increased risk for developing cardiovascular disease.