PGRN-RIKEN:Genetic Determinants of Cardiovascular Events while on Statins

Coronary heart disease (CHD) is an important public health problem in developed countries. Statins are effective in the prevention and treatment of CHD; nevertheless, many patients receiving statins still suffer cardiovascular events (CV) such as heart attack. Identifying genetic variants responsible for differential clinical responses to statins will not only allow individual patients at high residual risk to be targeted for additional therapies, but also will define new biologic pathways contributing to statin response, and thus new targets for future therapies. Accordingly, the goal of this study is to identify genetic variants associated with clinical CV in patients receiving statins. Subjects identified for study are of European descent and include 1718 subjects with CV while on statins (cases) and 4172 subjects without CV while on statins (controls). Key research resources utilized in this effort include VanderbiltD's BioVU DNA databank and associated Synthetic Derivative database of clinical information, and software tools developed to identify drugs and clinical events using Electronic Health Record-derived structured and unstructured ("free text") data. Most cases and controls identified include three data types: ICD-9 codes, medication regimens, and medical test results. Genotyping, using IlluminaD's Infinium HumanOmniExpressExome BeadChip (OmniExpressExome), was performed by the RIKEN Integrative Medical Sciences Center (IMS) and supported by the Pharmacogenomics Research Network (PGRN)-RIKEN IMS Global Alliance.]]>
Major Adverse Cardiac Events while on statins– Phenotype DefinitionCase Inclusion: AMI on statins: Case definition (all three conditions required): At least two ICD9 code for AMI or other acute and subacute forms of ischemic heart disease within a five-day window Confirmed lab within the same time window Statin prescribed prior to the AMI event in medical records at least 180 days Revascularization while on statin: Case definition (both conditions required): At least one revascularization CPT code Statin prescribed prior to the revascularization event in medical records at least 180 days Case Exclusion: No diagnosis code for AMI, other acute and subacute forms of ischemic heart , or historical AMI assigned previously No revascularization CPT codes assigned previously No MACE (Major Adverse Cardiovascular Events) found in previous problem list by NLP Control definition Statin prescribed No diagnosis code for AMI, other acute and subacute forms of ischemic heart, or historical AMI assigned previously No revascularization CPT codes assigned previously No MACE found in previous problem list by NLP Controls match cases by age, gender, statin type (e.g. simvastatin), and statin exposure.]]>