Familial hypercholesterolemia is a genetic disorder characterized by particularly high levels of LDL-cholesterol since birth. This condition leads to early development of atherosclerotic lesions that expose patients to a high risk of premature cardiovascular events.
It is an autosomal dominant disease, primarily associated with a mutation in the gene encoding the receptor for low-density lipoproteins. This causes a reduction of specific receptors for LDL and consequently an insufficient removal of LDL from circulation.
Even other genetic alterations can cause the phenotype of familial hypercholesterolemia, such as mutations in PCSK9 and ApoB genes.
There are two forms of the disease: the heterozygous form and the homozygous form. The first is less severe, has an incidence of 1 case per 500 individuals.
The homozygous form is much rarer with a prevalence of 1 case every 160,000-300,000 individuals. It is more severe both in metabolic and clinical terms, with myocardial infarction that can occur before 10th year of age.
Although the genetical mutations involved in this disease are various, a positive genetic test can differentiate a subject with familial hypercholesterolemia from a subject simply hypercholesterolemic. Genetic diagnosis also helps identify the disease among family members.
The short-term efficacy of statin therapy in patients with familiar hypercholesterolemia, even when administered in children, is well defined, but until now there were no evidence of its long-term efficacy in the prevention of cardiovascular diseases.
A recent study, published in the New England Journal of Medicine, sought to assess long-term efficacy of a treatment with statins, when begun in infancy, in patients with familial hypercholesterolemia.
The study recruited 214 patients with familial hypercholesterolemia, genetically confirmed in 98% of cases. All had previously participated in another study that had evaluated the efficacy and safety of a treatment with pravastatin during a two-year follow-up.
This new research extended the observation period up to an average of 18 years, comparing affected subjects, 95 unaffected siblings and 156 affected parents.
Participants were subjected to carotid intima-media thickness measurements with ultrasound assessments.
Among the patients with familial hypercholesterolemia, 79% have taken a lipid-lowering drug therapy, starting at an average age of 14 years.
The drugs used were pravastitin, atorvastatin, rosuvastatin or simvastatin, alone or in combination with ezetimibe or PCSK9 inhibitors.
The results showed a clear efficacy of statin treatment with a reduction in the average level of LDL-cholesterol from 237.3 to 160.7 mg per deciliter, corresponding to a 32% decrease compared to the baseline level.
The goal of the treatment, namely a reduction of LDL-cholesterol below 100 mg per deciliter, however, was achieved only in 20% of patients.
In the group of parents with familial hypercholesterolemia, 26% had a cardiovascular event before the age of 40. Survival without cardiovascular disease at 39 years was 99% among patients with familial hypercholesterolemia who had started statin therapy in infancy and 74% among affected parents.
None of the adults who had received care since childhood died for cardiovascular disease during follow-up. In the group of affected parents, 7% of subjects died before the age of 40, in all cases due to a myocardial infarction.
The average progression of carotid intima-media thickness was comparable in patients with familial hypercholesterolemia and in unaffected siblings, with annual variations of 0.0056 mm and 0.0057 mm, respectively.
This study confirms as statin therapy is not only able to reduce LDL-cholesterol but also to slow the progression of atherosclerotic disease.
The long-term follow-up also allowed to demonstrate how the beginning of this therapy since infancy can reduce the risk of cardiovascular diseases in adulthood.
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