Abstract 1349: Evaluation of Endothelial Function, Subclinical Coronary Atherosclerosis and Liposoluble Vitamins in a Family with Hypoalphalipoproteinemia Due to a Rare Mutation in the Apolipoprotein A-I gene (Q[-2]X)
A rare mutation of autossomal co-dominant transmission called Q[−2]X in the apolipoprotein (Apo) A-I gene was previously described in one Canadian kindred and associated with early onset of atherosclerosis. Total deletion of the entire AI/CIII/AIV gene complex another cause of hypoalphalipoproteinemia (hypoalpha) is associated with liposoluble vitamin (LSV) deficiency.
Objective: Evaluate endothelial function, subclinical atherosclerosis and LSV vitamin levels in a family with the Q[−2]X mutation in the ApoA-I gene.
Methods: Endothelial function was assessed by flow-mediated vasodilatation (FMD) and subclinical atherosclerosis by calcium score quantification using the Agaston method and by non-invasive angiography with a 16-detector multislice computed tomography scanner (MSCT). A,D, E LSV were determined by HPLC.
Results: 6 affected individuals (age 46.0±19.0, HDL-c 17.0±17.0 mg/dL), two homozygous, and 6 age and sex matched controls (age 41.0±7, HDL-c 51±8.0 mg/dL) were evaluated. The 2 homozygous, one with 39 and other 41 year old had HDL-C of 4 and 2 mg/dL respectively, had undetectable Apo AI levels and presented extensive xantomas in the back and buttocks. The hypoalpha group showed impaired FMD compared to controls (6.94 ±3.34 % Vs. 12.2 ± 4.4%, p=0.042). However, nitroglycerin induced similar degrees of vasodilation in both groups (12.8 ±7.7 Vs. 19.6 ± 5.28%, p=0.13). Five of the affected subjects presented calcified and non-calcified plaques visualized by MSCT and four presented calcium scores above the 75 th percentile for age and sex (Mean Agatston score 159±222). One homozygous had been previously submitted to CABG and the other presented atherosclerotic plaques with severe obstruction according to the CT angio scan in spite the fact that he was asymptomatic for CAD. LSV levels were normal in both hetero and homozygous patients. Conclusion:The (Q[−2]X) mutation was associated with impaired FMD and severely calcified and non-calcified coronary plaques. No deficiencies in LSV were found. Our results show for the first time that endothelial function is altered in these subjects and confirms the previous finding that subjects with this mutation are at an increased risk of atherosclerosis.