The Low-Density Lipoprotein Receptor Genotype Is a Significant Determinant of the Rebound in Low-Density Lipoprotein Cholesterol Concentration After Lipoprotein Apheresis Among Patients With Homozygous Familial Hypercholesterolemia.

Abstract

In homozygous familial hypercholesterolemia (HoFH) caused by mutations in the low-density lipoprotein (LDL) receptor ( LDLR ) gene, patients with 2 receptor-negative mutations have higher cholesterol concentrations and coronary heart disease risk than patients with double receptor-defective mutations.1 Pharmacological treatment is insufficient to achieve an efficient reduction in LDL-cholesterol (C) or lipoprotein (a) (Lp(a)) concentrations in patients with HoFH, and repetitive long-term lipoprotein apheresis (LA) remains the gold-standard therapy. LA induces an acute decrease in LDL-C and Lp(a) concentrations, which is then followed by a rebound in the following days. The rebound after LA constitutes a major determinant of LA efficacy because it directly affects the average concentrations between treatments, considered the best estimate of the physiological effects of long-term LA.2 However, our understanding of the determinants of rebound after treatment in LDL-C and Lp(a) is limited.2 This study aimed to determine the extent to which the LDLR genotype modulates the rebound after LA in LDL-C and Lp(a) concentrations among patients with HoFH. We hypothesized that the rebound in LDL-C and Lp(a) concentrations is greater among patients with receptor-negative HoFH than among patients with receptor-defective HoFH. Data on all consecutive LA treatments performed between August 2008 and February 2016 among patients with HoFH with genetically defined defective/defective LDLR mutations (n=3), negative/negative LDLR mutations (n=8), and defective/negative LDLR mutations (n=4) treated at the CHU de Quebec-Universite Laval were collected. For each patient, the compiled data included: (1) date of LA, (2) cumulative number of LA treatments received, (3) interval between LA treatments, (4) LA system used, (5) volume of filtered plasma per treatment, (6) duration of treatments, (7) lipoprotein concentrations before and after LA, and (8) cumulative interval since the first compiled LA treatment. Data on …