title: 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.
  
  
  OBJECTIVE
  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.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Diederik F
authors.initials: DF
authors.lastname: van Wijk
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Barbara
authors.initials: B
authors.lastname: Sjouke
authors.affiliation: Cardiac MR PET CT Program and Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Amparo
authors.initials: A
authors.lastname: Figueroa
authors.affiliation: Cardiac MR PET CT Program and Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Hamed
authors.initials: H
authors.lastname: Emami
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Fleur M
authors.initials: FM
authors.lastname: van der Valk
authors.affiliation: Cardiac MR PET CT Program and Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Megan H
authors.initials: MH
authors.lastname: MacNabb
authors.affiliation: Cardiac MR PET CT Program and Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Linda C
authors.initials: LC
authors.lastname: Hemphill
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands; Department of Internal Medicine I, Christian-Albrechts University Kiel, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Dominik M
authors.initials: DM
authors.lastname: Schulte
authors.affiliation: Department of Nephrology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Marion G
authors.initials: MG
authors.lastname: Koopman
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands; Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, New York.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Lobatto
authors.affiliation: Department of Nuclear Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Hein J
authors.initials: HJ
authors.lastname: Verberne
authors.affiliation: Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, New York.
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands; Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, New York.
authors.forename: Willem J M
authors.initials: WJ
authors.lastname: Mulder
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.affiliation: Cardiac MR PET CT Program and Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: atawakol@partners.org.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Tawakol
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands. Electronic address: e.s.stroes@amc.uva.nl.
authors.forename: Erik S G
authors.initials: ES
authors.lastname: Stroes
mesh_terms: D000368:Aged; D001158:Arteries / Q000473:pathology*; D050197:Atherosclerosis / Q000097:blood; D001781:Blood Component Removal / Q000379:methods*; D016022:Case-Control Studies; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000150:complications / Q000628:therapy*; D007249:Inflammation / Q000150:complications / Q000628:therapy*; D008074:Lipoproteins / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods; D011446:Prospective Studies; D012307:Risk Factors; D014057:Tomography, X-Ray Computed
chemical_list: D008078:Cholesterol, LDL; D008074:Lipoproteins; D019788:Fluorodeoxyglucose F18
keywords: PET/CT imaging; atherosclerosis