Methods for assessing the risk for development of cardiovascular disease
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 severity of a disease or evaluating response to treatment for such a disease as, for instance, cardiovascular disease.
1. 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 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;
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.
2. The method of claim 1 wherein the HDL tyrosine oxidation product is an apo A1 oxidation product.
3. The method of claim 1 , 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.
4. The method of claim 1 wherein the cardiovascular disease is atherosclerosis.
5. The method of claim 1 wherein the cardiovascular disease is associated with renal disease or renal failure.
6. The method of claim 1 wherein the HDL oxidation product is 3-nitrotyrosine.
7. The method of claim 1 wherein the HDL oxidation product is 3-chlorotyrosine.
8. The method of claim 1 wherein the HDL oxidation product is o′,o′-dityrosine.
9. The method of claim 1 wherein the assessing is determining risk for developing cardiovascular disease.
10. The method of claim 1 wherein the assessing is determining response of the cardiovascular disease to a treatment.
11. The method of claim 1 wherein the assessing is quantifying the severity of the cardiovascular disease.
12. The method of claim 1 , 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.
13. The method of claim 1 , wherein said biological sample is plasma or urine.
14. The method of claim 1 , wherein measuring said HDL oxidation product is performed by immunoassay or flow cytometry.
15. The method of claim 14 wherein said measuring is performed by a method selected from the group consisting of an enzyme-linked immunosorbent assay (ELISA), a lateral flow assay, a fluorescent polarization assay, a time-resolved fluorescence assay, a microparticle capture assay, a capillary electrophoresis assay, HPLC and a fluorescence immunoassay.
16. The method of claim 1 , wherein said measuring is performed by spectrophotometry.
17. A method for assessing risk for developing cardiovascular disease comprising the steps of:
A) obtaining a biological sample from a subject;
B) measuring 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.
18. The method of claim 17 wherein the HDL oxidation product is an apo A1 oxidation product.
19. The method of claim 17 , 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.
20. The method of claim 17 wherein the cardiovascular disease is atherosclerosis.
21. The method of claim 17 wherein the cardiovascular disease is associated with renal disease or renal failure.
22. The method of claim 17 , wherein the HDL tyrosine oxidation product is 3-nitrotyrosine.
23. The method of claim 17 , wherein the HDL tyrosine oxidation product is 3-chlorotyrosine.
24. The method of claim 17 , wherein the HDL tyrosine oxidation product is o′,o′-dityrosine.