Non-Invasive methods to Determine Vulnerable Plaque Burden in Subjects
Methods, kits, and systems for determining vulnerable plaque burden in a subject. The methods involve measuring an amount of at least one biomarker in a blood sample from the subject, wherein the at least one biomarker is selected from the group consisting of vascular endothelial growth factor-A (VEGF), cardiac troponin I (cTnI), and matrix metalloproteinase-9 (MMP-9). The concentration of these biomarkers in a sample from the subject are used to determine vulnerable plaque burden in the subject.
1 . A method for determining vulnerable plaque burden in a subject comprising:
measuring an amount of at least one biomarker in a blood, serum or plasma sample from the subject, wherein the at least one biomarker is selected from the group consisting of vascular endothelial growth factor-A (VEGF), cardiac troponin I (cTnI), and matrix metalloproteinase-9 (MMP-9);
comparing the amount of the at least one biomarker in the biological sample from the subject to a threshold concentration representing the concentration of the at least one biomarker in a population of normal healthy control subjects, and
determining vulnerable plaque burden in the subject when the concentration of at least one biomarker in the sample is greater than the threshold concentration.
2 . The method of claim 1 , wherein the MMP-9 is total MMP-9 (tMMP-9).
3 . The method of claim 1 , wherein vulnerable plaque burden is determined when the concentrations of at least two biomarkers in the sample are greater than the threshold concentrations.
4 . The method of claim 1 , wherein vulnerable plaque burden is determined when the concentrations of VEGF, cTnI and MMP-9 in the sample are greater than the threshold concentrations.
5 . The method of claim 1 , wherein vulnerable plaque burden is symptomatic of cardiovascular disease.
6 . A method for determining vulnerable plaque burden in a subject comprising:
measuring the concentration of one or more biomarkers selected from the group consisting of VEGF, cTnI and MMP-9 in a blood, serum or plasma sample from a patient,
standardizing the biomarker concentrations in the sample to threshold concentrations for the biomarkers in a population of normal healthy controls to create a ratio of the concentrations in the sample and the threshold concentrations,
wherein the ratios represent the vulnerable plaque burden in the subject.
7 . A method for determining vulnerable plaque burden in a subject comprising:
measuring an amount of at least two biomarkers selected from VEGF, cTnI or MMP-9 in a blood, serum or plasma sample from a patient,
standardizing the biomarker concentrations in the sample to threshold concentrations of the biomarkers in a population of normal healthy controls to create ratios of the concentrations in the test sample and the threshold concentrations,
adding the ratios to create a score representing vulnerable plaque burden in the subject.
8 . The method as in claim 7 , further comprising normalizing the score representing vulnerable plaque burden in the subject on a scale of 1-100.
9 . The method of claim 7 , wherein a score of 1 represents the detection of the least amount of vulnerable plaque and 100 represents the detection of the most vulnerable plaque.
10 . The method as in any one of claim 1 , wherein measuring the amount of VEGF, cTnI or MMP-9 comprises:
contacting the sample with an antibody specific for the VEGF, cTnI and MMP-9, and
determining the amount of specific binding between the antibody and the VEGF, cTnI and MMP-9 in the sample.
11 . The method of claim 11 , wherein the measuring is conducted with a single molecule counting assay.
12 . The method of claim 11 , wherein the antibody for VEGF, cTnI, or MMP-9 binds to a portion or derivative of VEGF, cTnI, and MMP-9.