Cardiovascular disease
Inventors
Salas Pérez-Rasilla, Eduardo • Marrugat De La Iglesia, Jaume • Elosua Llanos, Roberto • Castillo Fernandez, Sergio • Salgado Gomez, Joan • Ordovás Munoz, José Maria
Assignees
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Publication Number
US-11814673-B2
Publication Date
2023-11-14
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, Procamor 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 means for carrying out said method.
Core Innovation
The invention relates to a method for reclassifying and/or predicting cardiovascular disease or cardiovascular events in a human subject by combining classical coronary risk factors with polymorphisms detected at a specific nucleotide position. A biological sample isolated from a human subject is used to detect the identity of at least the nucleotide at position 27 within nucleic acid sequences of SEQ ID NOs: 2, 3, 5, and 8, to detect the presence of polymorphisms at least at said position.
The detected polymorphisms contribute a risk conferred by a weighted number of risk alleles present for each polymorphism, which is combined with a risk conferred by one or more classical coronary risk factors based on respective weighted values of each classical coronary risk factor for the human subject. The method calculates a risk of the human subject having a cardiovascular disease or event using a cardiovascular risk function that combines the classical coronary risk-factor contribution and the polymorphism risk contribution.
After calculating the risk, the method selects the human subject evaluated as having an elevated risk for preventative and/or therapeutic treatment. The selected human subject is then administered an agent selected from hypolipemic capabilities, anticoagulant, antiplatelet agent, thrombolytic agent, antithrombotic, antiarrhythmic agent, an agent that prolongs repolarization, antihypertensive agent(s), vasodilator, diuretic, inotropic agent, and/or antianginal agent.
The described approaches further support the calculation of risk using survival/hazard and event probability calculations, including formulations with baseline survival and a summation of weighted contributions. Dependent claim refinements specify a risk endpoint as the probability of fatal or non-fatal myocardial infarction or angina within a 10-year period, and they define embodiments including mathematical forms such as Weibull survival and separation into coronary and non-coronary cardiovascular risk components.
Claims Coverage
The independent claim is clm-00001. The claim set further includes dependent claim refinements, including survival/hazard formulation, Weibull-based 10-year risk, a specific endpoint and time horizon, selected sets of classical coronary risk factors, and narrowed treatment-agent options.
Position-27 polymorphism detection in specified SEQ ID nucleic acid sequences
Obtaining a biological sample isolated from a human subject and detecting the identity of at least the nucleotide at position 27 within the nucleic acid sequences of SEQ ID NOs: 2, 3, 5, and 8 to detect the presence of polymorphisms at least at said position.
Combined cardiovascular risk function from classical risk factors and weighted risk alleles
Calculating a risk of the human subject having a cardiovascular disease or event using a cardiovascular risk function that combines a risk conferred by one or more classical coronary risk factors based on respective weighted values and a risk conferred by the detected polymorphisms based on a weighted number of risk alleles present for each polymorphism.
Elevated-risk subject selection for preventative and/or therapeutic treatment
Selecting the human subject evaluated in the risk calculation as having an elevated risk for preventative and/or therapeutic treatment for a cardiovascular disease or event.
Cardiovascular agent administration to the elevated-risk subject
Administering to the selected human subject an agent with hypolipemic capabilities, an anticoagulant, an antiplatelet agent, a thrombolytic agent, an antithrombotic, an antiarrhythmic agent, an agent that prolongs repolarization, an antihypertensive agent, a vasodilator, a diuretic, an inotropic agent, and/or an antianginal agent.
Survival/hazard-based cardiovascular risk calculation
Using a cardiovascular risk function in which risk is computed using survival/free-of-coronary-events structure and contributions combining classical coronary risk-factor terms and genetic-variant/polymorphism terms, based on weighted values including hazard ratio betas and risk allele counts.
Weibull-based 10-year cardiovascular event risk with coronary and non-coronary components
Computing baseline Weibull survival for a given age, deriving 10-year survival and event risk during follow-up, and computing 10-year cardiovascular event risk as the sum of coronary cardiovascular risk and non-coronary cardiovascular risk.
10-year fatal or non-fatal myocardial infarction or angina endpoint
Wherein the assessed risk is the probability that the human subject will present a fatal or non-fatal myocardial infarction or angina within a 10-year period.
Specified classical coronary risk factors and subject-specific values
Selecting one or more specified classical coronary risk factors and determining respective values for those selected risk factors for the human subject.
Hypolipemic agent narrowed to HMG-CoA reductase inhibitor or bile acid sequestrant
Using an agent with hypolipemic capabilities that is either an HMG-CoA reductase inhibitor or a bile acid sequestrant.
Overall, claim coverage centers on detecting polymorphisms at nucleotide position 27 in specified SEQ ID NOs and incorporating the resulting weighted risk-allele contribution with classical coronary risk factors in a cardiovascular risk function. The method then selects elevated-risk subjects and administers cardiovascular agents, with dependent claims specifying survival/hazard or Weibull-based 10-year event calculations and a particular 10-year myocardial infarction/angina endpoint, as well as narrowing certain sets of classical risk factors and hypolipemic agent options.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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