Biomedical subjects

Joep C Defesche

Publications and source records attributed to Joep C Defesche.

22 records · Page 2Linked to original sources

PubMed2003

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.

Adult↗

PubMed2003

Identification of a new mutation, S305C, in exon 7 of the low-density lipoprotein receptor gene in a Brazilian family with homozygous familial hypercholesterolemia.

DNA analysis of the low-density lipoprotein receptor gene of a young Brazilian man, suffering from an extreme form of hypercholesterolemia, revealed the presence of two mutations, thereby confirming the diagnosis of homozygous familial hypercholesterolemia (FH). The first mutation was a mutation frequently found in Brazilian patients with FH, termed C660X or FHLebanese. The second mutation, in which a serine residue was replaced by a cysteine at amino acid position 305 (S305C) was a new mutation never described before. S305C was inherited from the proband's mother, who was of Italian descent. The occurrence of LDL receptor gene mutations of Lebanese and Italian origin in Brazil underlines the genetic heterogeneity of the Brazilian population.

Adult↗

PubMed2002

Low-density lipoprotein receptor gene mutations and cardiovascular risk in a large genetic cascade screening population.

BACKGROUND: A large cohort of patients with familial hypercholesterolemia (FH), free from selection for cardiovascular disease (CVD), and their unaffected relatives was collected by genetic cascade screening and examined for the influence of different mutations of the LDL receptor gene on lipoprotein levels and the risk of CVD. Multivariate analyses with adjustment for age, sex, and specific family ties were performed. METHODS AND RESULTS: Significant variation of LDL levels was observed among 399 patients with FH with different mutations. Null alleles were associated with more severely elevated LDL cholesterol, whereas the frequent N543H/2393del9 mutation led to less elevated LDL cholesterol. The type of mutation did not influence HDL cholesterol levels. Patients with FH had CVD 8.5 times more often compared with their unaffected relatives (RR, 8.54; 95% CI, 5.29 to 13.80). The N543H/2393del9 mutation was associated with a smaller increase of risk compared with other mutations (P<0.0001). After exclusion of families with the N543H/2393del9 mutation, null alleles and other allele mutations no longer differed with regard to LDL cholesterol levels and CVD risk. CONCLUSIONS: LDL receptor mutations only partly contributed to the variation of LDL cholesterol levels and cardiovascular burden in FH. Additional, so far unidentified, familial risk factors must underlie the differences of CVD risk, most likely independent of lipids and lipoproteins.

Adolescent↗

PubMed2002

Phenotypic variability in familial hypercholesterolaemia: an update.

Heterozygous familial hypercholesterolaemia is among the most common inherited dominant disorders, and is characterized by severely elevated LDL-cholesterol levels and premature cardiovascular disease. Although the cause of familial hypercholesterolaemia is monogenic, there is a substantial variation in the onset and severity of atherosclerotic disease symptoms. Additional atherogenic risk factors of environmental, metabolic and genetic origin, in conjunction with the LDL receptor defect, are presumed to influence the clinical phenotype in familial hypercholesterolaemia. The present review discusses recent developments in this field.

Chromosome Deletion↗