ABSTRACT
OBJECTIVES: Children with Hutchinson-Gilford Progeria Syndrome (HGPS) die of severe premature atherosclerosis at an average age of 13 years. Although the LMNA gene defect responsible for this "premature aging syndrome" has been identified, biological mechanisms underlying the accelerated atherosclerosis are unknown. We determined whether children with HGPS demonstrate abnormalities in known biomarkers for cardiovascular disease (CVD) risk. STUDY DESIGN: We quantified serum lipids, lipoproteins, C-reactive protein (CRP), and adiponectin in children with HGPS and age-matched control children. RESULTS: HDL cholesterol (P < .0001) and adiponectin (P < .001) concentrations decreased significantly with increasing age in HGPS but not in control children. There was a positive correlation between these variables in HGPS ( P < .0001) but not control children. Mean total cholesterol, LDL and HDL cholesterol, triglyceride, and median CRP levels were similar between HGPS and control children (all P > .05). CONCLUSIONS: Declining HDL cholesterol and adiponectin with advancing age may contribute to accelerated atherosclerotic plaque formation in HGPS. Several factors frequently associated with CVD risk in normal aging (elevated CRP, total and LDL cholesterol) showed no difference and are unlikely to influence CVD risk in HGPS. HDL and adiponectin may represent significant mediators and potential therapeutic targets for atherosclerosis in HGPS.