Increased Intima-Media Thickness in Carriers of the LDL-Receptor Defective Gene versus Noncarriers with Newly Detected Asymptomatic Severe Hypercholesterolemia

Abstract

The data on the examination of early vascular alterations in carriers of molecular defects of the low-density lipoprotein-receptor (LDL-R) in comparison to noncarriers with severe hypercholesterolemia are controversial. To examine the difference between patients with severe hypercholesterolemia, who are carriers and noncarriers of LDL-R defective gene, with respect to their functional (flow-mediated vasodilation) and structural (intima-media thickness of carotid artery) characteristics of arterial wall. A total of 250 hypercholesterolemic patients were enrolled. Biochemistry parameters were examined by routine methods. The molecular biological analysis included-R3500Q-mutation in the Apolipoprotein-B (Apo-B) gene, LDL-R gene mutation and polymorphism (and the promoter region), as large rearrangements. Determination of flow-mediated vasodilation and intima-media thickness of common carotid artery was performed with Hewlett Packard Sonos 5500, using automated computer software MedicaSoft. IMT.lab. There was no significant difference between the groups with respect to total cholesterol, LDL, HDL, Apo-B, Apolipoprotein A(1) (Apo-A(1) ), asymmetric dimethylarginine (ADMA), homocysteine, and cellular adhesion molecules. The Apo-B/Apo A(1) index differed significantly (t = 11.23, P < 0.001) between the two groups and this difference was found even after adjustment for age and gender. There was no significant difference with respect to the endothelial dependent and independent vasodilatation between the examined groups (P > 0.05). We were founded a significantly higher carotid IMT in the carriers versus noncarriers. This significant difference was confirmed after adjustment for age and gender. Statistically significant correlations we were founded between IMT mean and age (log) (r(xy) = 0.45; P < 0.01), cholesterol × years score (log) (r(xy) = 0.53; P < 0.01), Apo-B/A(1) (log) (r(xy) = 0.66; P < 0.001) in the group of the carriers. Backward selection process selected Apo-B/A(1) as the most important statistically significant factor related to IMT mean of common carotid artery (F = 105.22; P = 0.001; R(2) = 0.72). Our data demonstrate that carriers of the LDL-R defective gene have a higher carotid IMT and Apo B/Apo A(1) index than noncarriers, whereas no difference between the groups was found with respect to the level of lipid parameters, ADMA, total homocysteine, cell adhesion molecules and %FMD. Apo-B/A(1) is a predictor of IMT mean in the group of the carriers of the LDL-receptor gene.