US 6,309,888 B1Granted

Detection and determination of the stages of coronary artery disease

AssigneeLeuven Research & Development VZW

InventorsPaul N. Holvoet, Désiré J. Collen

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Abstract

A method having clinically sufficient degree of diagnostic accuracy for detecting the presence of coronary artery disease in a human patient from the general population and for distinguishing between the stages of the disease in that patient is disclosed. The stages are, first, the non-acute stage, which is either asymptomatic coronary artery disease or stable angina, second, the acute stage known as unstable angina, and, third, the acute stage known as acute myocardial infarction. The diseased state (as opposed to the non-diseased state) is indicated by the clinically significant presence of a first marker in a sample from the patient. The presence of one of the two acute stages, unstable angina or acute myocardial infarction, is indicated by the clinically significant presence of a second marker in a sample from the patient. The presence of the more severe acute stage known as acute myocardial infarction is indicated by the clinically significant presence of a third marker in a sample from the patient. Preferably the first marker comprises OxLDL, the second marker comprises MDA-modified LDL, and the third marker is a troponin. Preferably the OxLDL and MDA-modified LDL are detected using monoclonal antibodies that can detect the presence of those markers in undiluted human plasma at concentrations as low as 0.02 milligrams/deciliter.

Claims54

Dependent claims

A method having a clinically sufficient degree of diagnostic accuracy for detecting the presence of and for distinguishing between or among non-acute and acute stages of coronary army disease for a human patient from the general population, the non-acute stage of coronary artery disease big either asymptomanic coronary artery disease or stable angina and the acute stages of coronary artery disease being unstable angina and acute myocardial infraction, the method comprising performing step (b) and performing at least one of steps (a) and (c):

(a) testing a sample from the patient for a clinically significant pressure of a first marker whose presence above a predetermined level can indicate with a very high degree of diagnostic accuracy the presence of coronay artery disease, the first marker being a first atherogenic protein;
(b) testing a sample from the patient for a clinically significant presence of a second marker whose presence above a predetermined level can indicate with a very high degree of diagnostic accuracy the presence of an acute stage of coronary artery disease, the second marker being a second atherogenic protein;
and
(c) testing a sample from the patient for a clinically significant presence of a third marker whose presence above a predetermined level can indicate with a high degree of diagnostic accuracy the presence of acute myocardial infarction, the third maker being a heart protein;
(d) the diagnosis based on the results of step (b) and at least one of steps (a) and (c) being:
(i) the absence of coronary artery disease if none of the first, second, and third markers is present above its respective predetermined level;
(ii) non-acute coronary artery disease if the first marker but neither the second or third marker is present above its respective predetermined level;
(iii) unstable angina if each of the first and second markers but not the third marker is present above its respective predetermined level;
(iv) acute myocardial infarction of atherosclerotic origin if each of the first, second, and third markers is present above its respective predetermined level;
and
(v) acute myocardial infarction of non-atherosclerotic orign if neither of the first and second markers but the third marker is present above its respective predetermined level.

8 more elements

A method having a clinically sufficient degree of diagnostic accuracy for detecting the presence of and for distinguishing between or among non-acute and acute stages of coronary artery disease for a human patient from the general population, the non-acute stage of coronary artery disease being either asymptomaic coronary artery disease or stable angina and the acute stages of coronary artery disease being unstable angina and acute myocardial infarction, the method comprising the steps:

(a) testing a sample from the patient using an immunological assay for a clinically significant presence of OxLDL containing at least 60 substituted lysine residues per apo B-100 moiety, its presence above a predetermined level being able to indicate with a very high degree of diagnostic accuracy the presence of coronary artery disease, the assay employing at least one monoclonal antibody having a high affinity for the OxLDL;
(b) testing a sample from the patient using an immunological assay for a clinically significant presence of MDA-modified LDL containing at least 60 substituted lysine residues per apo B-100 moiety, its presence above a predetermined level being able to indicate with a very high degree of diagnose accuracy the presence of an acute stage of coronary artery disease, the assay employing at least one monoclonal antibody having a high affinity for the MDA-modified LDL;
and
(c) optionally a sample from the patient for a clinically significant presence of a third marker whose presence above a predetermined level can indicate with a high degree of diagnostic accuracy the presence of acute myocardial infraction, the third marker being a heart protein;
(d) the diagnosis based on the result of steps (a) and (b) and of optional step (c) being:
(i) the absence of coronary artery disease if none of the first, second, and third markers is present above its respective predetermined level;
(ii) non-acute coronary artery disease if the first marker but neither the second or third marker is present above its respective predetermined level;
(iii) unstable angina if each of the first and second markers but not the third marker is present above its respective predetermined level;
(iv) acute myocardial infraction of atherosclerotic origin if each of the first, second, and third markers is present above its respective predetermined level;
and
(v) acute myocardial infarction of non-atherosclerotic origin if neither of the first and second markers but third marker is present above its respective predetermined level.

8 more elements

A method having a clinically sufficient degree of diagnostic accuracy for detecting the presence of and for distinguishing between or among non-acute and acute stages of coronary artery disease for a human patient from the general population, the non-acute stage of coronary artery disease being either asymptomatic coronary artery disease or stable angina and the acute stages of coronary artery disease being unstable angina and acute myocardial infarction, the method comprising the steps:

(a) testing a sample from the patient using an immunological assay for a clinically significant presence of OxLDL containing at least 60 substituted lysine residues per apo B-100 moiety, its presence above a predetermined level being able to indicate with a very high degree of diagnostic accuracy the presence of coronary artery disease, the assay employing at least one monoclonal antibody having a high affinty for the OxLDL;
(b) testing a sample from the patient using an immunological assay for a clinically significant presence of MDA-modified LDL containing at least 60 substituted lysine residues per apo B1-100 moiety, its presence above a predetermined level being able to indicate with a very high degree of diagnostic accuracy the presence of an acute stage of coronary artery disease, the assay employing at least one monoclonal antibody having a high affinity for the MDA-modified LDL;
and
(c) testing a sample from the patient for a clinically significant presence of a heart protein whose presence above a predetermined level can indicate with a high degree of diagnostic accuracy the presence of acute myocardial infarction;
(d) the diagnosis based on the results of steps (a), (b), and (c) being:
(i) the absence of coronary artery disease if none of the first, second, and third markers is present above its respective predetermined level;
(ii) non-acute coronary artery disease if the first marker but neither the second or third marker is present above its respective predetermined level;
(iii) unstable angina if each of the first and second markers but not the third marker is present above its respective predetermined level;
(iv) acute myocardial infarction of atherosclerotic origin if each of the first, second, and third markers is present above its respective predetermined level;
and
(v) acute myocadial infarction of non-atherosclerotic origin if neither of the first and second markers but the third marker is present above its respective predetermined level.

8 more elements

Dependencies are inferred from the claim text.

Facts

Application: 09/148,158Filed 4 Sep 1998
Granted: 30 Oct 2001
Term ends: Not estimatedThe source records don’t support an estimate.

Classification15 codes

G01N 33/721
Involving blood pigments, e.g. haemoglobin, bilirubin or other porphyrins; involving occult blood: haemoglobin
G01N 33/6893
Involving proteins, peptides or amino acids: related to diseases not provided for elsewhere
G01N 33/92
Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing:…
G01N 2800/32
Detection or diagnosis of diseases: cardiovascular disorders