From the Guidelines
Genetic lipid disorders, such as Familial Hypercholesterolemia (FH), are autosomal dominant inherited conditions characterized by hypercholesterolemia due to increased LDL levels, xanthomas, premature coronary heart disease (CHD), and a family history of one or more of these.
Key Characteristics of FH
- Hypercholesterolemia: Elevated LDL cholesterol levels, often above 190 mg/dL 1
- Xanthomas: Presence of xanthomas, which are deposits of cholesterol in the skin and tendons
- Premature CHD: Increased risk of coronary heart disease, with angina, heart attacks, or death typically occurring in men between 30 and 50 years, and in women between 50 and 70 years 1
- Family history: A positive family history of premature atherosclerotic cardiovascular disease and events
Diagnosis of FH
- Genetic testing: The most accurate way to diagnose FH is by genetic testing, which identifies the presence of pathogenic variants that impair LDL receptor function and cause hypercholesterolemia 1
- Clinical criteria: Diagnosis can also be made based on clinical criteria, including elevated LDL cholesterol levels, presence of xanthomas, and a positive family history 1
- Biochemical factors: Biochemical factors, such as elevated lipoprotein(a) levels and decreased HDL cholesterol levels, can also support a diagnosis of FH 1
Treatment of FH
- Statins: Patients with FH should be aggressively treated with statins at a young age to reduce the risk of CHD 1
- Lifestyle advice: Lifestyle advice, such as a healthy diet and regular exercise, should also be offered and supported 1
- Cascade testing: Cascade testing to identify affected relatives should be undertaken to prevent premature CHD in family members 1
From the Research
Definition and Prevalence of Genetic Lipid Disorders
- Genetic lipid disorders, such as Familial Hypercholesterolemia (FH), are a group of conditions that affect millions of individuals worldwide, often going undiagnosed 2.
- FH is a common, inherited disorder of cholesterol metabolism, usually an autosomal dominant disorder caused by inherited mutations in the APOB, LDLR, and PCSK9 genes 3.
- The incidence of heterozygous FH is 1:200-250, whereas that of homozygous FH is 1:100,000-160,000 3.
Characteristics and Diagnosis of Familial Hypercholesterolemia
- FH is characterized by elevated low-density lipoprotein (LDL) cholesterol and premature cardiovascular disease, with a prevalence of approximately 1 in 200-500 for heterozygotes in North America and Europe 4.
- Diagnosis can usually be made using a combination of clinical characteristics such as family history, lipid levels, and genetic testing 5.
- The Dutch Lipid Clinical Criteria are a helpful diagnostic tool used to diagnose FH 3.
Treatment and Management of Familial Hypercholesterolemia
- Early treatment is vital, as the clinical outcome is related to the degree and duration of exposure to elevated LDL-C levels 5.
- Statins remain the first-line therapy in most cases, but monotherapy is usually inadequate to control elevated LDL-C levels 5.
- Additional therapy with ezetimibe, bile acid sequestrants, and newer classes of pharmacotherapy, such as lomitapide, mipomersen, and monoclonal antibodies to PCSK9, may be required 3, 5.
- Lipoprotein apheresis may be required when multiple pharmacotherapies are inadequate, especially in the homozygous form 5.
Importance of Genetic Testing and Early Detection
- Genetic testing for FH is essential for diagnosis and treatment, as it can help identify patients who are at high risk of cardiovascular events 6.
- Early identification and treatment of patients, as well as screening of relatives, can significantly reduce the risk of premature disease 5.
- The importance of genetic testing for FH is highlighted by the fact that patients with positive genetic testing may not achieve lower LDL-cholesterol levels without medication, whereas patients with negative genetic testing may be able to achieve lower levels through lifestyle changes alone 6.