Diederik F van Wijk1, Barbara Sjouke1, Amparo Figueroa2, Hamed Emami2, Fleur M van der Valk1, Megan H MacNabb2, Linda C Hemphill2, Dominik M Schulte3, Marion G Koopman4, Mark E Lobatto5, Hein J Verberne6, Zahi A Fayad7, John J P Kastelein1, Willem J M Mulder5, G Kees Hovingh1, Ahmed Tawakol8, Erik S G Stroes9. 1. Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands. 2. Cardiac MR PET CT Program and Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 3. 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. 4. Department of Nephrology, Academic Medical Center, Amsterdam, the Netherlands. 5. Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands; Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, New York. 6. Department of Nuclear Medicine, Academic Medical Center, Amsterdam, the Netherlands. 7. Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, New York. 8. Cardiac MR PET CT Program and Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: atawakol@partners.org. 9. Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands. Electronic address: e.s.stroes@amc.uva.nl.
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.
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 FHpatients. METHODS: In total, 38 subjects were recruited: 24 FHpatients and 14 normolipidemic controls. All subjects underwent FDG-PET imaging at baseline. Twelve FHpatients 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 FHpatients, 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 FHpatients 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: Lotte C A Stiekema; Erik S G Stroes; Simone L Verweij; Helina Kassahun; Lisa Chen; Scott M Wasserman; Marc S Sabatine; Venkatesh Mani; Zahi A Fayad Journal: Eur Heart J Date: 2019-09-01 Impact factor: 29.983
Authors: Ruud S Kootte; Loek P Smits; Fleur M van der Valk; Jean-Louis Dasseux; Constance H Keyserling; Ronald Barbaras; John F Paolini; Raul D Santos; Theo H van Dijk; Geesje M Dallinga-van Thie; Aart J Nederveen; Willem J M Mulder; G Kees Hovingh; John J P Kastelein; Albert K Groen; Erik S Stroes Journal: J Lipid Res Date: 2015-01-05 Impact factor: 5.922
Authors: Sophie J Bernelot Moens; Simone L Verweij; Fleur M van der Valk; Julian C van Capelleveen; Jeffrey Kroon; Miranda Versloot; Hein J Verberne; Henk A Marquering; Raphaël Duivenvoorden; Liffert Vogt; Erik S G Stroes Journal: J Am Soc Nephrol Date: 2016-10-31 Impact factor: 10.121
Authors: Robert A Hegele; Samuel S Gidding; Henry N Ginsberg; Ruth McPherson; Frederick J Raal; Daniel J Rader; Jennifer G Robinson; Francine K Welty Journal: Arterioscler Thromb Vasc Biol Date: 2015-09-16 Impact factor: 8.311