Nonpharmacological lipoprotein apheresis reduces arterial inflammation in familial hypercholesterolemia.

Abstract

BACKGROUND:

Patients with familial hypercholesterolemia (FH) are characterized by elevated atherogenic lipoprotein particles, predominantly low-density lipoprotein cholesterol (LDL-C), which is associated with accelerated atherogenesis and increased cardiovascular risk.

OBJECTIVES:

This study used (18)F-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) to investigate whether arterial inflammation is higher in patients with FH and, moreover, whether lipoprotein apheresis attenuates arterial wall inflammation in FH patients.

METHODS:

In total, 38 subjects were recruited: 24 FH patients and 14 normolipidemic controls. All subjects underwent FDG-PET imaging at baseline. Twelve FH patients who met the criteria for lipoprotein apheresis underwent apheresis procedures followed by a second FDG-PET imaging 3 days (range 1 to 4 days) after apheresis. Subsequently, the target-to-background ratio (TBR) of FDG uptake within the arterial wall was assessed.

RESULTS:

In FH patients, the mean arterial TBR was higher compared with healthy controls (2.12 ± 0.27 vs. 1.92 ± 0.19; p = 0.03). A significant correlation was observed between baseline arterial TBR and LDL-C (R = 0.37; p = 0.03) that remained significant after adjusting for statin use (β = 0.001; p = 0.02) and atherosclerosis risk factors (β = 0.001; p = 0.03). LDL-C levels were significantly reduced after lipoprotein apheresis (284 ± 118 mg/dl vs. 127 ± 50 mg/dl; p < 0.001). There was a significant reduction of arterial inflammation after lipoprotein apheresis (TBR: 2.05 ± 0.31 vs. 1.91 ± 0.33; p < 0.02).

CONCLUSIONS:

The arterial wall of FH patients is characterized by increased inflammation, which is markedly reduced after lipoprotein apheresis. This lends support to a causal role of apoprotein B-containing lipoproteins in arterial wall inflammation and supports the concept that lipoprotein-lowering therapies may impart anti-inflammatory effects by reducing atherogenic lipoproteins.

• Authors: Diederik F van Wijk, Barbara Sjouke, Amparo Figueroa, Hamed Emami, Fleur M van der Valk, Megan H MacNabb, Linda C Hemphill, Dominik M Schulte, Marion G Koopman, Mark E Lobatto, Hein J Verberne, Zahi A Fayad, John J P Kastelein, Willem J M Mulder, G Kees Hovingh, Ahmed Tawakol, Erik S G Stroes
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 64 Issue 14 Pg. 1418-26 (Oct 07 2014) ISSN: 1558-3597 [Electronic] United States
• PMID: 25277610 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Cholesterol, LDL
• Lipoproteins
• Fluorodeoxyglucose F18

Topics

• Aged
• Arteries (pathology)
• Atherosclerosis (blood)
• Blood Component Removal (methods)
• Case-Control Studies
• Cholesterol, LDL (blood)
• Cross-Sectional Studies
• Female
• Fluorodeoxyglucose F18 (chemistry)
• Humans
• Hyperlipoproteinemia Type II (complications, therapy)
• Inflammation (complications, therapy)
• Lipoproteins (chemistry)
• Male
• Middle Aged
• Pilot Projects
• Positron-Emission Tomography (methods)
• Prospective Studies
• Risk Factors
• Tomography, X-Ray Computed