Genetic findings reported approximately 9 years ago in the Journal indicated that rare sequence variants in the gene encoding proprotein convertase subtilisin–kexin type 9 serine protease (PCSK9) were associated with significantly lower long-term plasma levels of low-density lipoprotein (LDL) cholesterol. The observed reduction in LDL cholesterol levels was similar to that attained with moderate-intensity statin therapy. The benefits of lifelong lowering of LDL cholesterol levels were substantial; a 47 to 88% lower risk of coronary heart disease was observed over a period of 15 years in middle-aged persons with such genetic polymorphisms. Further genetic studies indicated that PCSK9 activity was a major determinant of plasma levels of LDL cholesterol in humans.
Lowering LDL Cholesterol Is Good, but How and in Whom?