Variation in Serum PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9), Cardiovascular Disease Risk, and an Investigation of Potential Unanticipated Effects of PCSK9 Inhibition

PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors reduce serum LDL (low-density lipoprotein) cholesterol (LDL-C) by increasing uptake in the liver. Although some long-term trials have evaluated their safety, broad investigations of outcomes over the lifetime, leveraging genetic variation in serum PCSK9, have seldomly been conducted. We investigated effects of these variants on a range of outcomes to explore unanticipated effects of long-term PCSK9 inhibition.