Characterization of low-density lipoprotein cholesterol-lowering efficacy for atorvastatin in a population-based DNA biorepository

Abstract

The Marshfield Clinic Personalized Medicine Research Project (PMRP) represents a large population-based biobank located in central Wisconsin. To position the PMRP database for large-scale pharmacogenetic association studies in the context of lipid-lowering therapy, we constructed an electronic phenotyping algorithm to quantify exposure and dose-response for atorvastatin, the most commonly prescribed lipid-lowering agent within this population. The resulting datasets were used to generate five distinct parameters for atorvastatin-induced changes in low-density lipoprotein (LDL) cholesterol level: (i) pretreatment, baseline LDL level [E(0)]; (ii) absolute reduction in LDL; (iii) relative reduction in LDL; (iv) potency [ED(50)]; and (v) maximal efficacy [E(max)]. These parameters will facilitate the efficient application of electronic phenotyping for drug outcomes in the context of large pharmacogenetic association studies.