Cholesterol Acyltransferase Gene Mutations Have Accelerated Atherogenesis as Assessed by Carotid 3.0-T Magnetic Resonance Imaging: Carriers of Lecithin

• Published in: Journal of the American College of Cardiology 2011-12, Vol.58 (24), p.2481-2487
• Main Authors: DUIVENVOORDEN, Raphael, HOLLEBOOM, Adriaan G, STROES, Erik S. G, VAN DEN BOGAARD, Bas, NEDERVEEN, Aart J, DE GROOT, Eric, HUTTEN, Barbara A, SCHIMMEL, Alinda W, HOVINGH, G. Kees, KASTELEIN, John J. P, KUIVENHOVEN, Jan Albert
• Format: Article
• Language: English
• Subjects: Age; Apolipoproteins; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood pressure; Body mass index; Cardiology; Cardiology. Vascular system; Cholesterol; Diabetes; Enzymes; General aspects. Genetic counseling; Hypertension; Lipids; Lipoproteins; Medical genetics; Medical sciences; NMR; Nuclear magnetic resonance; Plasma; Software; Studies; Triglycerides; Ultrasonic imaging; Veins & arteries
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2010.11.092

Objectives The aim of this study was to investigate the role of reduced lecithin: cholesterol acyltransferase (LCAT) function on atherogenesis using 3.0-T carotid magnetic resonance imaging (MRI) and B-mode ultrasound. Background The role of low high-density lipoprotein cholesterol as a causal factor in atherogenesis has recently been questioned. LCAT plays a key role in high-density lipoprotein cholesterol metabolism. Methods Carotid 3.0-T MRI and B-mode ultrasound measurements were performed in 40 carriers of LCAT gene mutations and 40 controls, matched for age. Patients with cardiovascular disease were excluded. Results Carriers had 31% lower LCAT activity levels and 38% decreased high-density lipoprotein cholesterol levels (both p < 0.001 vs. controls). Carriers presented with a 10% higher normalized wall index (0.34 ± 0.07 vs. 0.31 ± 0.04, p = 0.002), a 22% higher mean wall area (17.3 ± 8.5 mm2vs. 14.2 ± 4.1 mm2, p = 0.01), and a 22% higher total wall volume (1,039 ± 508 mm3vs. 851 ± 247 mm3, p = 0.01 vs. controls) as measured by MRI. The prevalence (20 vs. 5, p = 0.002) and the total volume (102 mm3vs. 3 mm3) of atherosclerotic plaque components on MRI relating to lipid-rich tissue or calcification were also higher in carriers than in controls. All differences retained significance after adjustment for age, sex, blood pressure, low-density lipoprotein cholesterol, body mass index, smoking, and family history of cardiovascular disease. Common carotid intima-media thickness measured with ultrasound was increased in carriers by 12.5% (0.72 ± 0.33 mm vs. 0.64 ± 0.15 mm, p = 0.14). Conclusions Carriers of LCAT gene mutations exhibit increased carotid atherosclerosis, indicating an increased risk of cardiovascular disease. The present findings imply that increasing LCAT activity may be an attractive target in cardiovascular prevention strategies.