Compliance of the aorta in two diseases affecting vascular elasticity,familial hypercholesterolemia and diabetes: a MRI study

Arterial elasticity changes in familial hypercholesterolemia (FH) and diabetes mellitus (DM) with different but overlapping mechanisms. We compared aortic elasticity between 19 FH patients with the same mutation, 18 type 2 DM patients, and 30 controls, all aged 48 to 64. They underwent aortic magnetic resonance imaging, risk-factor assessment, and carotid and femoral ultrasound measurements. All patients were on adequate cardiovascular medication including statins and had established coronary heart disease (CHD). FH patients had longer-duration CHD (13.3 ± 7.7 years) than did DM patients (5.0 ± 3.1). Aortic compliance in the descending thoracic (DM 0.38 ± 0.14 vs control 0.53 ± 0.19, P = 0.032) and abdominal aorta (DM 0.45 ± 0.20 vs control 0.66 ± 0.25, P = 0.011) was lower in DM patients than in controls, whereas no significant difference existed between FH patients and controls. Carotid and femoral intima-media thickness was greater in FH and DM patients than in controls with no difference between patient groups. Carotid or femoral plaques appeared in 15 (79%) FH and in 10 (56%) DM patients. One control had a femoral plaque. Five FH patients showed stenosis, occlusion or both in carotid arteries. In our opinion, DM patients’ lower compliance reflect mainly arterial media affecting arteriosclerosis, while FH patients’ plaque status and longer duration of CHD suggest more advanced atherosclerosis. The FH patients may therefore be at increased risk for atherothrombotic events. However, due to small patient material, larger confirmatory studies are needed.     

Influence of apolipoprotein E genotypes on plasma lipid and lipoprotein concentrations: Results from a segregation analysis in pedigrees with molecularly defined familial hypercholesterolemia

Familial hypercholesterolemia (FH) is a monogenic disorder caused by mutations in the low-density lipoprotein (LDL) receptor gene. Large variations in plasma lipids and lipoprotein levels have been observed in FH families. These may be caused by other environmental and genetic factors of which apolipoprotein E (apo E) is a candidate. The possible influence of apo E polymorphism on components of variation in plasma LDL-C, triglycerides, high-density lipoprotein cholesterol (HDL-C), and lipoprotein(a) (Lp(a)) levels was investigated in 235 members of 14 families with FH. Sex- and age-adjusted mean LDL-C was influenced significantly by the apo E genotype in non-FH subjects (P ≤ .01), and a similar trend was observed in FH cases. Mean plasma levels of triglyceride, HDL-C, and Lp(a) were not significantly different across the apo E genotypes in FH and in non-FH family members. Complex segregation analysis was first applied to these sex- and age-adjusted data. In addition to the major gene involved in LDL-C levels (i.e., the LDL receptor gene), there was evidence for a nontransmitted environmental major factor in addition to polygenic effect that explained the mixture of distributions in TG and a major effect in addition to polygenic loci which influenced Lp(a) levels. There was no evidence for a single major factor controlling HDL-C levels in these pedigrees. When the segregation models allowed apo E regression coefficients to be ousiotype (class) specific, the results suggested that apo E genotypes have a significant effect on LDL-C, TG, and Lp(a) levels. In conclusion, the analysis presented here supports the concept that the apo E gene has an important role in the regulation of plasma lipid and lipoproteins in FH. © 1996 Wiley-Liss, Inc.