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[Prevention of coronary heart disease in familial hypercholesterolemia]
1Departemente Innere Medizin und Forschung, Kantonsspital Basel.
Insights
Familial hypercholesterolemia (FH) and familial defective apolipoprotein B-100 (FDB) are genetic lipid disorders increasing atherosclerosis risk. Early identification and intensive lipid-lowering treatment are crucial for improving longevity and reducing cardiovascular events.
Area of Science:
- Genetics and Molecular Biology
- Cardiovascular Medicine
- Metabolic Disorders
Context:
- Familial hypercholesterolemia (FH) and familial defective apolipoprotein B-100 (FDB) are autosomal-dominant inherited lipid disorders.
- These conditions result from defects in the low-density lipoprotein (LDL) receptor or apolipoprotein B-100.
- Both disorders significantly elevate the risk of premature atherosclerosis, particularly affecting coronary arteries.
Purpose:
- To highlight the genetic basis and clinical characteristics of FH and FDB.
- To emphasize the increased risk of premature atherosclerosis and excess mortality associated with these conditions.
- To underscore the importance of early diagnosis and intensive lipid-lowering therapy.
Summary:
- Mutations in the LDL receptor gene cause FH, while mutations in the apolipoprotein B-100 gene cause FDB.
- Patients experience a substantially higher risk of coronary heart disease, with coronary deaths being significantly more frequent in younger adults.
- Cardiovascular lesions can regress with intensive lipid-lowering therapy, indicating the potential for disease modification.
Impact:
- Early identification of FH and FDB patients and their relatives is critical for timely intervention.
- Intensive lipid-lowering treatment, including medication and diet, can mitigate serious prognosis and improve longevity.
- This research emphasizes the need for proactive management of genetic lipid disorders to prevent severe cardiovascular outcomes.
Abstract:
Familial forms of isolated hypercholesterolemia are inherited autosomal-dominantly and are caused by defects of the low-density lipoprotein (LDL) receptor protein or its ligand, the apolipoprotein B-100, the exclusive apolipoprotein moiety of the LDL particles. Mutations at the LDL receptor gene locus (more than 150 different mutations have been described up to now) lead to familial hypercholesterolemia (FH); the only mutation at the apolipoprotein B-100 gene locus described in detail so far leads to the so-called familial defective apolipoprotein B-100 (FDB). Both lipid disorders are characterized by an increased risk for premature atherosclerosis involving primarily the coronary arteries. An increased risk for coronary heart disease can be expressed statistically by the excess mortality. In particular, individuals between the age of 20 and 59 are affected by an excess mortality; coronary deaths are approximately 100 times more frequent in patients between 20 and 39 with familial forms of hypercholesterolemia than within the normal population. On the other hand, in patients with myocardial infarctions before the age of 60, the diagnosis of FH is approximately 20 to 30 times more frequent than within the normal population. A regression of cardiovascular lesions subsequent to an intensive lipid-lowering therapy has clearly been demonstrated in patients with familial forms of hypercholesterolemia. Because of the serious prognosis of untreated familial forms of isolated hypercholesterolemia with respect to longevity, it is important to identify patients and their relatives with FH and FDB as early as possible and to treat them, besides a lipid-lowering diet, intensively with lipid-lowering drugs.