From the Guidelines
Familial hypercholesterolemia (FH) is typically diagnosed when LDL cholesterol levels exceed 190 mg/dL in adults or 160 mg/dL in children, especially with a family history of premature cardiovascular disease. For heterozygous FH, LDL levels commonly range from 190-400 mg/dL, while the more severe homozygous form can present with LDL levels above 500 mg/dL, sometimes reaching 1000 mg/dL, as indicated in the 2022 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk 1. The International Atherosclerosis Society guidance for implementing best practice in the care of familial hypercholesterolaemia also supports these LDL levels for diagnosis and treatment, emphasizing the importance of early diagnosis and aggressive treatment to reduce the risk of cardiovascular events 1. Key considerations in managing FH include:
- Starting treatment with high-intensity statins like atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily.
- Adding additional medications as needed, such as ezetimibe 10 mg daily, PCSK9 inhibitors (evolocumab 140 mg every 2 weeks or alirocumab 75-150 mg every 2 weeks), or bempedoic acid 180 mg daily.
- Aiming to reduce LDL by at least 50% from baseline, with ideal levels below 100 mg/dL for primary prevention or below 70 mg/dL for those with established cardiovascular disease.
- Considering lipoprotein apheresis for patients who do not achieve guideline-recommended LDL-cholesterol goals despite maximally tolerated combination drug therapy, particularly those with homozygous FH or severe heterozygous FH with progressive atherosclerotic cardiovascular disease 1. Early diagnosis and aggressive treatment are crucial because FH patients have significantly elevated lifetime risk of cardiovascular events due to lifelong exposure to high LDL levels, with untreated heterozygous FH patients facing a 20-fold increased risk of premature heart disease.
From the Research
Familial Hypercholesterolemia and LDL Levels
- Familial hypercholesterolemia (FH) is characterized by markedly elevated LDL-cholesterol (LDL-C) levels and an increased risk of premature atherosclerotic cardiovascular disease 2.
- The disorder remains mostly undetected and its management is often suboptimal, with high-intensity statins being the standard treatment for patients with FH 2.
- However, LDL-C levels in most patients treated with statin monotherapy remain above those recommended by guidelines 2, 3.
Treatment Options for Lowering LDL Levels
- Combination therapy, such as treatment with statins plus ezetimibe, has been successful in lowering LDL-C levels further 2, 3.
- Other treatment options, including mipomersen, lomitapide, and PCSK9 inhibitors, have also been shown to reduce LDL-C levels in patients with FH 2, 3, 4.
- Aggressive LDL cholesterol-lowering therapy, such as coadministration of rosuvastatin, ezetimibe, and colestimide, can improve the lipid profile of patients with FH 5.
Diagnostic Criteria and Clinical Severity
- Diagnostic criteria for familial hypercholesterolaemia include an elevated LDL cholesterol level and a family history of hypercholesterolaemia or (premature) CVD 4.
- Clinical severity depends on the nature of the gene that harbours the causative mutation, among other factors, and is further modulated by the type of mutation 4.
- Lifelong LDL cholesterol-lowering treatment substantially improves CVD-free survival and longevity in patients with FH 4.