FP775CHILDREN WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (FH) ON LIPOPROTEIN APHERESIS − A FOUR YEAR FOLLOW−UP

Abstract

Introduction and Aims: Familial hypercholesterolemia (FH) is an autosomal co-dominant severe monogenic form of hypercholesterolemia. The risk of premature coronary heart disease (CHD) is dependent on the degree and duration of exposure to elevated LDL-cholesterol (LDL-C) levels. Early diagnosis and initiation of effective treatment is imperative. In some individuals lipidapheresis may be necessary also in childhood to keep LDL-C in normal range. Special attention should be drawn to other known atherosclerotic risk factors such as obesity and hypertension. Method(s): 5 children from 2 families (7-14 years of age) with LDL-receptor mutations (p.Trp577Arg and p. Asp354Gly) were treated with lipidapheresis after a period of 12 months on insufficient therapy with atorvastatin and ezetimibe with LDL-C plasma concentration of above 300-500 mg/dL (7.8-12 mmol/L). Lipidapheresis was subsequently intensified in quality and quantity until a stable mean plasma LDL-C in normal levels had been reached. For cardiovascular outcome intima media thickness (IMT), pulse wave velocity (PWV), ambulatory blood pressure measurement (ABPM) and ambulatory arterial stiffness index (AASI) as well as echocardiographic doppler sonography were monitored once a year over a time period of 1-4 years. Coronary angio computer tomography (CT) was implemented into the follow-up program in the fourth year. Result(s): At the beginning of lipidapheresis all five patients had LDL-C plasma concentrations of above 300-500 mg/dL (7.8-12 mmol/L). After 7 months of lipidapheresis treatment LDL-C values were in the normal range of 120-170 mg/dl (3.1-4.4 mmol/l). 12,24, 36 and 48 months after having reached normal values, cardiovascular follow-up was performed. Despite normal LDL-C plasma concentrations without rebound, IMT and AASI in all 5 patients were above the 95th age related percentile in all follow-ups. PWV was below the 95th age related percentile. Results of echocardiography were unremarkable. The coronary angio CTscan showed no soft plaques in 3 of 5 patients after 4 years with lipid apheresis in which LDL-C was controlled in a range of 120-170 mg/dl (3.1-4.4 mmol/l). 2 patients have not undergone a CT scan yet. Conclusion(s): Despite intensive therapy, permanently normal LDL-C values and unremarkable coronary CT scans elevated IMT and AASI hint at an increased cardiovascular risk profile in our patients. Different from cutaneous cholesterol deposits that disappeared within months functional cardiovascular changes seem to take longer to regress. It may be important to start effective treatment as early in live as possible and to take other risk factors for atherosclerotic changes into account.