Diagnostic and prognostic methods for cardiovascular diseases and events
Inventors
RHYNE, Rhonda Fay • MAGARET, Craig Agamemnon • STROBECK, John Edward • JANUZZI, Jr., James Louis
Assignees
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Publication Number
US-10983135-B2
Publication Date
2021-04-20
Expiration Date
Abstract
Compositions and methods are provided for diagnosis and/or prognosis of cardiovascular diseases or events in a subject. In some embodiments, the method includes measuring and comparing the level of particular proteins to other proteins. In other embodiments, the method includes comparison with clinical variable information.
Core Innovation
The described cardiovascular prognostic and diagnostic panels, assays, and kits use selected protein biomarkers in biological samples to diagnose and/or prognose cardiovascular disease outcomes. Prognosis is based on biomarker levels and associated prognostic scoring, with prediction time horizons expressed within 30 to 365 days after sample draw and at longer time horizons. The document also provides diagnostic and prognostic biomarker sets, clinical variables that may be incorporated, and classification of results as positive or negative based on diagnostic or prognostic scores.
For obstructive CAD diagnosis, the document describes multibiomarker panels comprising at least about 1 and greater than 4 biomarkers, optionally combined with clinical variables. The clinical variables include age, sex, prior PCI/CABG, diabetes mellitus type 2, hemodialysis, and prior MI. Example panel compositions include adiponectin, apolipoprotein C-I (C-1), KIM-1, and midkine, together with clinical history variables.
For prognostic embodiments, the document describes panels for composite endpoints including CVD death/MI/stroke, all-cause death/MI/stroke, CVD death/MI, and MI alone. Example prognostic biomarker sets include KIM-1, NT-proBNP, osteopontin, and TIMP-1, and the document provides example panel embodiments and scoring systems for these outcomes.
Claims Coverage
The independent claim family covers determining whether a patient is at high risk for myocardial infarction, stroke, or cardiovascular death using a prognostic score calculated from a defined multi-biomarker assay, followed by administering cardiovascular disease pharmacologic agents when the score indicates high risk. The inventive features focus on the biomarker combination KIM-1, NT-proBNP, osteopontin, and TIMP-1, the prognostic score calculation, and the conditional administration of cardiovascular pharmacologic agents.
Biomarker-based prognostic score for MI, stroke, and cardiovascular death
Obtaining or having obtained a biological sample; performing or having performed a biomarker assay for kidney injury molecule-1 (KIM-1), N terminal prohormone of brain natriuretic protein (NT-proBNP), osteopontin, and tissue inhibitor of metalloproteinases-1 (TIMP-1); and calculating a prognostic score based on the biomarker levels.
Conditional administration of cardiovascular pharmacologic agents based on high-risk prognostic score
Identifying the patient as having a prognostic score indicative of high risk of myocardial infarction, stroke or cardiovascular death, then administering one or more cardiovascular disease pharmacologic agents.
High-risk prediction within a 30-day timeframe
The prognostic score predicts the risk of cardiovascular death, myocardial infarct, or stroke within 30 days.
High-risk prediction within 0 to 365 days of sample draw
The prognostic score predicts the risk of cardiovascular death, myocardial infarct, or stroke within 0 to 365 days of sample draw.
Pharmacologic agent comprising a nitrate
The one or more cardiovascular disease pharmacologic agents comprise a nitrate.
Pharmacologic agent comprising a beta blocker
The one or more cardiovascular disease pharmacologic agents comprise a beta blocker.
Pharmacologic agent comprising an antiplatelet agent
The one or more cardiovascular disease pharmacologic agents comprise an antiplatelet agent.
Across the independent claim, the core claim coverage is the use of a prognostic score derived from a multi-biomarker assay to identify high-risk patients for MI, stroke, or cardiovascular death, followed by administering cardiovascular disease pharmacologic agents; dependent claims specify prediction time horizons and particular classes of cardiovascular pharmacologic agents.
Stated Advantages
Enables identifying patients with a prognostic score indicative of high risk of myocardial infarction, stroke or cardiovascular death for treatment with cardiovascular disease pharmacologic agents.
Documented Applications
Diagnosing and/or prognosing cardiovascular disease outcomes using biomarker-panel methods that calculate diagnostic/prognostic scores and classify results as positive or negative.
Treating patients at-risk of cardiovascular disease or having chest pain or discomfort in the shoulder, arm, back, neck or jaw by determining risk of MI, stroke, or cardiovascular death and administering cardiovascular pharmacologic agents accordingly.
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