Risk markers for cardiovacular disease

A method for characterizing a subject's risk of developing cardiovascular disease, comprising:

• determining levels of one or more oxidized apoA-I related biomolecules in a biological sample from the subject, wherein the one or more apoA-I-related biomolecules are selected from oxidized HDL, oxidized apoA-I, and an oxidized apoA-I peptide fragment, and
• wherein elevated levels of the one or more apoA-I-related oxidized biomolecules in the biological sample as compared to a control value or an internal standard indicates that the subject is at risk of developing cardiovascular disease.

A method for characterizing the near term risk of experiencing a major adverse cardiac event in a subject who is presenting with chest pain, comprising:

• determining levels of one or more oxidized apoA-I-related biomolecules in a biological sample from the subject, wherein said one or more apoA-I-related biomolecules is selected from oxidized HDL, oxidized apoA-I, and an oxidized apoA-I peptide fragment, and
• wherein elevated levels of the one or more apoA-I-related oxidized biomolecules in the biological sample as compared to a control value or an internal standard indicates that the subject is at risk of experiencing a major cardiac event.

A method for evaluating therapy in a subject suspected of having or diagnosed as having cardiovascular disease, comprising:

• determining levels of one or more oxidized apoA-I-related biomolecules in a biological sample taken from the subject prior to therapy and determining levels of the one or more of the oxidized apo-A1 related biomolecules in a corresponding biological sample taken from the subject during or following therapy,
• wherein a decrease in levels of the one or more oxidized apoA-I-related biomolecules in the sample taken after or during therapy as compared to levels of the one or more oxidized apo-A1-related biomolecules in the sample taken before therapy is indicative of a positive effect of the therapy on cardiovascular disease in the treated subject.

A method of assessing a subject's risk of experiencing a complication of cardiovascular disease, comprising

• comparing levels of one or more oxidized forms of a biomolecule in a biological sample from the subject with levels of said one or more oxidized forms of said biomolecule in a biological sample from a control population of subjects;
• wherein said biomolecule is oxidized HDL, oxidized apoA-I, one or more oxidized apoA-I peptide fragments, or combinations thereof, and
• characterizing the subject's risk of experiencing a complication of cardiovascular disease based upon levels of the one or more oxidized biomolecule in the subject's bodily sample in comparison to a control value derived from a control population of subjects.

A method of determining the near term risk of requiring medical intervention in a subject presenting with chest pain, comprising:

• assessing the level of a risk predictor in a bodily sample from the subject, wherein said risk predictor is oxidized HDL, oxidized apoA-I, an oxidized apoA-I peptide fragment, or any combination thereof,
• wherein the difference between the level of the risk predictor in the subject's bodily sample and the level of the risk predictor in a comparable bodily sample from the control population establishes the extent of the risk of requiring medical intervention near term in the subject.

A method of characterizing the risk of experiencing a subsequent acute cardiovascular event in a subject who has experienced one or more acute adverse cardiovascular events, comprising:

• determining levels of one or more of the oxidized apoA-I-related biomolecules in a biological sample taken from the subject at an initial time and in a corresponding biological sample taken from the subject at a subsequent time;
• wherein an increase in levels of the one or more oxidized apoA-I-related biomolecules in a biological sample taken at the subsequent time as compared to the initial time indicates that a subject's risk of experiencing a subsequent adverse cardiovascular event has increased.

A method for monitoring over time the status of cardiovascular disease (CVD) in a subject with CVD, comprising:

• determining the levels of one or more of the oxidized apoA-I-related biomolecules in a biological sample taken from the subject at an initial time and in a corresponding biological sample taken from the subject at a subsequent time, wherein am increase in levels of the one or more oxidized apoA-I-related biomolecules in a biological sample taken at the subsequent time as compared to the initial time indicates that a subject's CVD has worsened.

An antibody immunospecific for oxidized apoA-I, or an oxidized apoA-I peptide fragment, wherein said apoA-I peptide fragment is at least three amino acids in length and comprises one or more of the following amino acid residues:

• chlorotyrosine, nitrotyrosine, dityrosine, trihydroxyphenylalanine, dihydroxyphenylalanine, methionine sulphoxide residue, and tyrosine peroxide.

A kit comprising:

• one or more reagents for detecting oxidized apoA-I or an oxidized fragment of apoA-I, and
• one or more of the following printed materials:
• instructions for using said reagent in a method of assessing a test subject's risk of cardiovascular disease, information for assessing a test subjects risk cardiovascular disease, and recommendations for treating a subject who is determined to be at risk of cardiovascular disease.

A method of treating a person suspected of having or diagnosed as having cardiovascular disease, comprising:

• determining levels of one or more oxidized apoA-I-related biomolecules in a biological sample from the subject, wherein said one or more apoA-I-related biomolecules is selected from oxidized HDL, oxidized apoA-I, and an oxidized apoA-I peptide fragment, and
• where the levels of the one or more oxidized apoA-I-related biomolecules are elevated as compared to a control sample, providing interventional treatment to reduce the person's risk of a near term adverse cardiac event.

A method of treating a person suspected of having or diagnosed as having cardiovascular disease, comprising:

• determining levels of one or more oxidized apoA-I-related biomolecules in a biological sample from the subject, wherein said one or more apoA-I-related biomolecules is selected from oxidized HDL, oxidized apoA-I, and an oxidized apoA-I peptide fragment, and
• where the levels of the one or more oxidized apoA-I-related biomolecules are elevated as compared to a control sample, providing advice to the person to improve the person's long term cardiovascular health.

A method for treating a subject to reduce the risk of a cardiovascular disorder, comprising:

• determining levels of one or more oxidized apoA-I-related biomolecules in a biological sample from the subject, wherein said one or more apoA-I-related biomolecules is selected from oxidized HDL, oxidized apoA-I, and an oxidized apoA-I peptide fragment, and
• where the levels of the one or more oxidized apoA-I-related biomolecules are elevated as compared to a control sample an agent chosen from an anti-inflammatory agent, an antithrombotic agent, an anti-platelet agent, a fibrinolytic agent, a lipid reducing agent, a direct thrombin inhibitor, a glycoprotein IIb/IIIa receptor inhibitor, an agent that binds to cellular adhesion molecules and inhibits the ability of white blood cells to attach to such molecules, a calcium channel blocker, a beta-adrenergic receptor blocker, a cyclooxygenase-2 inhibitor, or an angiotensin system inhibitor, is administered to the subject.