New and emerging therapies for hyperlipidemia

Abstract

Three new biological pathways provide hope for patients poorly responsive to current lipid-lowering modalities. These patients fall into two large categories: one driven by genetic inheritance, the other by lifestyle choices mixed with other metabolic defects. Those born with loss-of-function PCSK9 alleles appear safe from harm with a significant difference in longevity from those without it. Blocking the function of PCSK9 has provided dramatic lowering of LDLC, by up-regulating the LDL receptor. For those with low levels of LDL receptors (familial hypercholesterolemia), two methods without LDL-receptor dependence have recorded significant LDL lowering. One of them provides a reduction in highly atherogenic small LDLC, as well as lowers triglyceride. This is associated with a reduction in apolipoprotein CIII, a key player in raising triglyceride and producing small LDLC.