Risk assessment for cardiovascular disease
Inventors
Heaton Walls, Matthew • Carrera, Marta • Marrugat De La Iglesia, Jaume • Elosua Llanos, Roberto
Assignees
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Publication Number
US-12077823-B2
Publication Date
2024-09-03
Expiration Date
Abstract
The invention relates to a method for the reclassification of a subject to a more appropriate risk assessment to that obtained using the algorithms for such risk estimation such us but not limited to Framingham, Regicor, Score, Procam or Qrisk based on the presence of different polymorphisms. The invention also relates to a method for determining the risk of suffering a cardiovascular disease by combining the absence or presence of one or more polymorphic markers in a sample from the subject with conventional risk factors for CVD as well as computer-implemented methods for carrying out the risk determination.
Core Innovation
The invention relates to cardiovascular risk assessment in a human subject by determining, in a sample isolated from the human subject, a presence of a polymorphism at position 27 within each nucleic acid sequence set forth in SEQ ID NOs: 2, 3, 4, 5, 7, 8, 9, 10, 11 or 16, 12, and 35. The presence at position 27 of a specified nucleotide in each SEQ ID NO is indicative of an elevated risk of having a cardiovascular event, and based on the presence of the polymorphisms, the method selects the human subject as having an elevated risk of a cardiovascular event.
The invention further relates to selecting a human subject for cardiovascular therapy and preventive cardiovascular therapy/measurements by determining polymorphisms at position 27 across the specified SEQ ID NO sets. In this selection, the presence at position 27 of specified nucleotides in the SEQ ID NOs is indicative of having a decreased response to a cardiovascular therapy, being in need of an early and aggressive cardiovascular therapy, or in need of a prophylactic cardiovascular treatment, and the human subject is selected as being in need of cardiovascular therapy or preventive cardiovascular therapy/measurements.
The invention also provides probability determination for presenting fatal or non-fatal myocardial infarction or angina over a 10 year period using classical risk factors and genetic variants comprising the polymorphism at position 27. A probability is computed using a formula that includes mean survival free of coronary events, logarithm of hazard ratio components for classical risk factors, and logarithm of hazard ratio components associated with genetic variants, including a genetic risk score and risk allele counts (0,1,2).
The invention further frames establishing therapeutical objectives of preventive treatments and/or therapeutical treatments by selecting a human subject based on the polymorphisms at position 27. The computed or selected outcomes are tied to administering therapeutic agents with hypolipemic capabilities and cardiovascular drug classes including anticoagulant, antiplatelet agent, thrombolytic agent, antithrombotic, antiarrhythmic agent, an agent that prolongs repolarization, antihypertensive agent, vasodilator, diuretic, inotropic agent, and/or antianginal agent.
Claims Coverage
The independent claims cover four related aspects of cardiovascular risk assessment and treatment selection using a polymorphism at nucleotide position 27 across specified SEQ ID NO sequence sets: selecting subjects as elevated risk and administering therapy, identifying subjects needing cardiovascular therapy or preventive measures due to decreased response or early/aggressive/prophylactic need, establishing therapeutical objectives for preventive and/or therapeutic treatments, and determining 10-year myocardial infarction/angina probability using classical risk factors and genotype-based hazard/survival models followed by administration of therapy.
Cardiovascular risk assessment by polymorphism presence at position 27 and therapy administration
Determining in a sample isolated from the human subject a presence of a polymorphism at position 27 within each nucleic acid sequence set forth in SEQ ID NOs: 2, 3, 4, 5, 7, 8, 9, 10, 11 or 16, 12, and 35, wherein specified nucleotide presence at position 27 is indicative of elevated risk; based on the presence of the polymorphisms, selecting the human subject as having an elevated risk of a cardiovascular event; administering to the selected human subject one or more agents including hypolipemic capabilities and cardiovascular therapy classes.
Identifying need for cardiovascular therapy or preventive measures based on decreased response or early/aggressive/prophylactic need from position 27 polymorphisms
Determining in a sample isolated from the human subject a presence in at least one allele of a polymorphism at position 27 within each nucleic acid sequence set forth in SEQ ID NOs: 2, 3, 4, 5, 7, 8, 9, 10, 11 or 16, 12, and 35, wherein specified nucleotide presence at position 27 is indicative of having a decreased response to a cardiovascular therapy, being in need of an early and aggressive cardiovascular therapy, or in need of a prophylactic cardiovascular treatment; based on the presence of the polymorphisms, selecting the human subject as being in need of cardiovascular therapy or preventive cardiovascular therapy/measurements; administering agents including hypolipemic capabilities and cardiovascular therapy classes.
Establishing therapeutical objectives using position 27 polymorphism determination and therapy selection
Determining in a sample isolated from the human subject a presence of a polymorphism at position 27 within each nucleic acid sequence set forth in SEQ ID NOs: 2, 3, 4, 5, 7, 8, 9, 10, 11 or 16, 12, and 35, wherein specified nucleotide presence at position 27 is indicative of the human subject being in need of the preventive treatments and/or the therapeutical treatments; based on the presence of the polymorphisms, selecting the human subject as being in need of cardiovascular therapy or preventive cardiovascular therapy/measurements for a cardiovascular event; administering agents including hypolipemic capabilities and cardiovascular therapy classes.
10-year myocardial infarction/angina probability using classical risk factors and hazard-ratio survival formulation with position 27 polymorphisms
Determining a probability of a human subject presenting a fatal or non-fatal myocardial infarction or angina in a 10 year period based on presence of 1 to P classical risk factors and 1 to J polymorphism genetic variants at position 27 within each specified SEQ ID NO set, wherein nucleotide presence at position 27 is specified; computing the probability using a formula involving mean survival free of coronary events, summatory functions over classical risk factors and genetic variants, logarithm of hazard ratio coefficients, and risk allele number copies (0,1,2); based on the probability determined, selecting the human subject as having an elevated probability; administering agents including hypolipemic capabilities and cardiovascular therapy classes.
Across the independent claims, the core inventive coverage is the use of polymorphisms at position 27 across specified SEQ ID NO sets to select human subjects as having elevated cardiovascular event risk or needing therapy/preventive measures, and to compute or determine 10-year probability of fatal or non-fatal myocardial infarction or angina using hazard-ratio or survival formulations that include classical risk factors and genetic variants at position 27, followed by administration of specified cardiovascular agent classes.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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