Long-term compliance with lipid-lowering medication after genetic screening for familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia is a common lipid disorder that predisposes to premature cardiovascular disease. Lipid-lowering treatment of affected individuals is widely advocated, and maximum benefit can be obtained if medication is started early. A screening program for familial hypercholesterolemia is ongoing in the Netherlands since 1994. To assess the extent of treatment and therapy compliance, patients were followed up for 2 years after the diagnosis was established. METHODS: Data were obtained by questionnaire. The 747 patients with familial hypercholesterolemia participating in the study were from the general community, and 62.4% were not receiving cholesterol-lowering medication. RESULTS: The overall percentage of treated patients had risen from 37.6% at screening to 92.5% 1 year later and then decreased to 85.9% 2 years after screening. During follow-up, 6.4% of patients discontinued their medication and 12.0% of untreated patients never started medication for various reasons, but in the majority of cases as advised by their own physicians. The mean reduction in low-density lipoprotein cholesterol levels in previously untreated patients was 30.1% (from 219 to 153 mg/dL [5.7 to 4.0 mmol/L]). For those already receiving treatment, an additional reduction of 10.3% (from 195 to 175 mg/dL [5.0 to 4.5 mmol/L]) was obtained. CONCLUSIONS: Most patients were receiving treatment 2 years after identification and had a positive attitude toward the screening program. However, the reduction of cholesterol levels still did not meet the internationally accepted goals of treatment. This underscores the fact that additional education is required to improve the treatment of individuals with familial hypercholesterolemia.

Association between increased arterial-wall thickness and impairment in ABCA1-driven cholesterol efflux: an observational study.

BACKGROUND: Decreased concentrations of HDL cholesterol are associated with increased cardiovascular risk. These concentrations are directly related to cholesterol efflux from cells-the first step and a key process in reverse cholesterol transport. Cholesterol efflux is mediated by the ATP-binding cassette A1 transporter (ABCA1), the rate-limiting step in the production of HDL. We aimed to assess the relation between cholesterol efflux, HDL concentrations, and arterial-wall changes in individuals with impaired ABCA1 function. METHODS: We investigated 30 individuals from families with ABCA1 mutations, and 110 controls matched for age, sex, and ethnic origin. We measured concentrations of HDL cholesterol in plasma and intima-media thickness of the carotid arteries by B-mode ultrasonography in all participants. We also measured cholesterol efflux from skin fibroblasts in nine individuals with ABCA1 mutations and in ten controls. FINDINGS: Individuals with ABCA1 mutations had lower amounts of cholesterol efflux, lower HDL cholesterol concentrations, and greater intima-media thicknesses than controls. An intima-media thickness at the upper limit of normal (0.80 mm) was reached by age 55 years in the ABCA1 heterozygotes, and at age 80 years in unaffected controls (p<0.0001). Additionally, strong positive correlations were seen between HDL cholesterol concentrations and cholesterol efflux (r=0.90, p=0.001), and negative correlations between apolipoprotein-AI-mediated (r=-0.61, p=0.030) and HDL-particle-mediated (r=-0.60, p=0.018) efflux and intima-media thickness in the ABCA1 mutation carriers. INTERPRETATION: These results show a direct relation between ABCA1-mediated cellular cholesterol efflux and arterial-wall thickness, and therefore suggest that increasing efflux could inhibit atherosclerosis progression before the manifestation of symptomatic cardiovascular disease.