Nonpharmacological Lipoprotein Apheresis Reduces Arterial Inflammation in Familial Hypercholesterolemia

• Published in: Journal of the American College of Cardiology Vol. 64; no. 14; pp. 1418 - 1426
• Main Authors: van Wijk, Diederik F., Sjouke, Barbara, Figueroa, Amparo, Emami, Hamed, van der Valk, Fleur M., MacNabb, Megan H., Hemphill, Linda C., Schulte, Dominik M., Koopman, Marion G., Lobatto, Mark E., Verberne, Hein J., Fayad, Zahi A., Kastelein, John J.P., Mulder, Willem J.M., Hovingh, G. Kees, Tawakol, Ahmed, Stroes, Erik S.G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.10.2014; Elsevier Limited
• Subjects: Aged; Arteries - pathology; atherosclerosis; Atherosclerosis - blood; Blood Component Removal - methods; Cardiology; Cardiovascular; Case-Control Studies; Cholesterol; Cholesterol, LDL - blood; Cross-Sectional Studies; Female; Fluorodeoxyglucose F18 - chemistry; Humans; Hyperlipoproteinemia Type II - complications; Hyperlipoproteinemia Type II - therapy; Inflammation - complications; Inflammation - therapy; Lipoproteins - chemistry; Low density lipoprotein; Male; Medical imaging; Middle Aged; PET/CT imaging; Pilot Projects; Positron-Emission Tomography - methods; Prospective Studies; Risk Factors; Tomography, X-Ray Computed; Veins & arteries; atherosclerosis; CRP; FH; LDL-C; TBR; IQR; Lp(a); 18FDG; CVD; HDL-C; CT; TG; SUV; PET/CT imaging; MDS; PET; BMI; C-reactive protein; low-density lipoprotein cholesterol; interquartile range; standardized uptake value; familial hypercholesterolemia; high-density lipoprotein cholesterol; 18F-fluorodeoxyglucose; target-to-background ratio; positron emission tomography; computed tomography; cardiovascular disease; body mass index; triglycerides; most diseased segment; lipoprotein(a)
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2014.01.088

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