Abstract 14969: The LDL Receptor Genotype Among Patients With Homozygous Familial Hypercholesterolemia is a Significant Determinant of the Rebound Increase in LDL-C Concentrations Following Lipoprotein Apheresis
Introduction: Lipoprotein apheresis (LA) is a reliable method to decrease LDL-C concentrations and remains the gold standard therapy in homozygous familial hypercholesterolemia (HoFH). Although it is well established that the LDL receptor (LDLR) genotype affects plasma LDL-C levels in both FH heterozygotes and HoFH, it is unclear whether the LDLR genotype is also associated with significant variability in the rebound increase in LDL-C levels following LA treatments.
Hypothesis: We hypothesized that the LDLR genotype modulates the rebound increase in LDL-C concentrations following LA treatments, HoFH patients with negative LDLR mutations having a greater rebound increase in LDL-C than HoFH patients with defective LDLR mutations.
Methods: Data from 2086 consecutive LA treatments performed between 2008 and 2016 on 15 HoFH patients with known LDLR mutations were analyzed. These data included: pre- and post-LA lipoprotein concentrations, the volume of filtered plasma (mL), LA system used (heparin-induced extracorporeal precipitation (HELP) vs. dextran-sulfate adsorption (DS)) and interval between treatments.
Results: The rebound increase in LDL-C concentrations following LA treatments was greater in HoFH with negative LDLR mutations than in those with defective LDLR mutations (+249% vs +98%, P=0.01). However, the magnitude of the reduction in LDL-C concentrations induced by LA was independent of the LDLR genotype (P=0.2). The interval between LA treatments was positively and independently associated with the magnitude of the rebound increase in LDL-C levels (β=+34.2%/week, P<0.0001). Finally, mean reductions in LDL-C levels induced by LA treatments were comparable for both systems (HELP: -64.8% vs. DS: -65.0%, P=0.8).
Conclusions: Our results indicate that the LDLR genotype modulates the rebound increase in plasma LDL-C concentrations following LA treatments and suggest that HoFH patients with negative LDL receptor mutations may benefit from more frequent LA treatments to reduce the rebound increase in LDL-C levels and their exposure to elevated concentrations of atherogenic lipoproteins.
Author Disclosures: J. Drouin-Chartier: None. A.J. Tremblay: None. J. Bergeron: None. B. Lamarche: Research Grant; Modest; CIHR. Other Research Support; Modest; Atrium Innovations. P. Couture: None.
- © 2016 by American Heart Association, Inc.