Atorvastatin Dose‐response for High‐density Lipoprotein Cholesterol in a Population‐Based DNA Biobank Cohort

Abstract

Statins have variable effects on high density lipoprotein (HDL) cholesterol. Prior data suggest that the atorvastatin dose‐response may be biphasic. The current study tests this hypothesis retrospectively, in a population‐based cohort. The Marshfield Clinic Personalized Medicine Research Project includes >19,000 participants. Using natural language processing (NLP) software, we linked drug dosage to fasting HDL cholesterol levels for 2432 PMRP participants exposed to atorvastatin during the course of their routine clinical care. Mean HDL level prior to atorvastatin exposure was 46.2 mg/dl (S.D. = 11.9, N=2432). Mean baseline HDL of females (Mean=50.2, S.D. = 12.2, N=1256) was higher than males (Mean =41.9, S.D. = 10.0, N=1176). The lowest initial dose (5 mg daily) resulted in an increase in mean HDL to 51.01 mg/dl (male=46.3, female=55.4). Beyond 5 mg, however, each subsequent doubling of the daily dose resulted in a linear decrease in the mean HDL level. This biphasic dose‐response was noted in both genders. At the maximum daily dose of 80 mg, mean HDL was 46.62 mg/dl (male=43.8, female=50.2). Funding source U01HL069757‐06