Abstract 239: LDL Apheresis Is Associated With a Reduction in Markers of Chronic Inflammation in Patients With Familial Hypercholesterolemia
Background: Familial Hypercholesterolemia is an inherited disease characterized by severely elevated levels of LDL cholesterol (LDL-C) and associated with premature coronary artery disease (CAD). LDL apheresis (LA) is indicated for management of CAD patients with LDL-C>200 mg/dl despite medical therapy. LA may reduce LDL-C concentrations by up to 70%; this in turn has been associated with regression of atherosclerosis. NMR measurement of signals corresponding to methyl group protons of glycoproteins (GlycA and GlycB) has recently been validated in prediction of atherosclerosis and chronic systemic inflammation. Studies have demonstrated a reduction in inflammatory cytokines with LA, but no study to date has evaluated the impact of LA on levels of glycoproteins as markers of chronic inflammation.
Objective: To determine the effect of LA on plasma levels of glycoproteins using a novel NMR based technique, and to correlate these findings with changes in lipoprotein subclasses.
Methods: Comprehensive NMR lipoprotein analysis was performed on serum obtained from seven subjects prior to and following LA sessions performed at two-week intervals (N = 47 paired samples). Three subjects had homozygous FH, three had heterozygous FH with CAD and/or LDL-C > 200 mg/dL, one patient had severe mixed dyslipidemia with CAD and LDL-C > 200 mg/dL.
Results: Mean GlycA and GlycB levels were 335±91 μmol/L and 125±31 μmol/L respectively prior to LA. Following LA treatment, there was a significant reduction in GlycA to 277±73 μmol/L (P<0.001) and in GlycB to 102±28 μmol/L (P<0.001). The reduction in GlycA was strongly correlated with a decrease in total small LDL particle number (r = 0.68, p < 0.001) and with a reduction in medium VLDL particle number (r = 0.52, P < 0.001). GlycB level was weakly correlated with small LDL (r = 0.39, P = 0.007) and IDL particle numbers (r = 0.32, P = 0.028). In addition, GlycA and GlycB levels were correlated to each other (r = 0.49, P < 0.001).
Conclusion: This is the first report of NMR detection of glycoproteins as inflammatory biomarkers in patients with severe dyslipidemia undergoing LA. LA was associated with a significant reduction in levels of both GlycA and GlycB, which correlated with reductions in LDL and VLDL particle number.
Author Disclosures: D.R. Lynch: None. D.A. Winegar: Employment; Significant; Liposcience Inc. M. Connelly: Employment; Significant; Liposcience Inc.. P.G. Yancey: None. R. Pourfarzib: Employment; Significant; Liposcience Inc. S. Fazio: Consultant/Advisory Board; Modest; Liposcience Inc. M.F. Linton: Consultant/Advisory Board; Modest; Liposcience Inc..
- © 2014 by American Heart Association, Inc.