Abstract 12617: Mutations in ABCA1 Are Associated With Increased Atherosclerosis: A 3.0 Tesla MRI Study
Background: The role of high density lipoprotein-cholesterol (HDL-c) as a protective factor against atherogenesis has been questioned following the absence of a relation between genetic variations associated with low HDL-c and cardiovascular outcome. A major gene in HDL metabolism is the ATP-binding cassette transporter (ABCA1), mediating cellular cholesterol efflux to prebeta HDL-particles. To more directly address the impact of life-long low HDL-c due to ABCA1 dysfunction on atherogenesis, we assessed the atherosclerotic burden in carriers of functional ABCA1 mutations using 3-Tesla magnetic resonance imaging (MRI) of the carotid arteries.
Methods and Results: MRI was performed in 37 carriers of ABCA1 gene mutations and 64 age- and sex-matched controls. Carriers were characterized by a 45% lower HDL-c levels (p<0.001), a 15% increase in mean wall area (0,19±0.06 cm² vs 0.16±0.06 cm², p=0.02), a 12% increase in normalized wall index (0.37±0.06 vs 0.33±0.05, p<0.001), and a 16% increase in mean wall thickness (0.83±0.21mm vs 0.70±0.18mm, p=0.002) compared to controls. After adjustment for age, gender, body mass index, systolic blood pressure, total cholesterol, HDL-cholesterol, statin use, smoking status, alcohol use and history of overt cardiovascular disease, the normalized wall index retained significance in carriers compared to controls (p=0.012).
Conclusion: Carriers of ABCA1 gene mutations are characterized by thickened carotid artery walls, reflecting an increased risk for cardiovascular disease. These findings imply that ABCA1-increasing strategies provide an attractive target to reduce cardiovascular risk.
- © 2011 by American Heart Association, Inc.