What lipid testing is most beneficial in familial hypercholesterolemia (Familial Hypercholesterolemia)?

From the Guidelines

For familial hypercholesterolemia, LDL-Cholesterol (LDL-C) should be used as the primary lipid analysis for screening, risk estimation, diagnosis, and management. This is based on the 2016 ESC/EAS guidelines for the management of dyslipidaemias 1. The guidelines recommend LDL-C as the primary target for treatment, with goals of < 1.8 mmol/L (70 mg/dL) for patients at very high CV risk, or a reduction of at least 50% if the baseline LDL-C is between 1.8 and 3.5 mmol/L (70 and 135 mg/dL).

Key points to consider in the management of familial hypercholesterolemia include:

• LDL-C is the primary lipid analysis for diagnosis and management
• Additional testing may include apolipoprotein B (apoB) levels and lipoprotein(a) [Lp(a)] measurement
• Genetic testing for mutations in the LDLR, APOB, PCSK9, and LDLRAP1 genes can confirm the diagnosis
• Cascade screening of first-degree relatives is essential once FH is diagnosed in an index case
• Early identification through appropriate lipid testing is crucial as FH patients have significantly increased risk of premature cardiovascular disease

The use of LDL-C as the primary lipid analysis is supported by the European Society of Cardiology (ESC) guidelines, which recommend measuring Lp(a) in patients at high risk of cardiovascular disease (CVD) and targeting levels below 50 mg/dL 1. However, LDL-C remains the primary target for treatment, and high-intensity statins and other lipid-lowering therapies can substantially reduce the risk of premature cardiovascular disease in FH patients.

From the Research

Lipid Testing for Familial Hypercholesterolemia

The most beneficial lipid testing for familial hypercholesterolemia is a topic of ongoing research and debate.

• Routine lipid testing is recommended to identify patients with familial hypercholesterolemia (FH) 2.
• Genetic testing can facilitate the identification of FH cases who may be missed by clinical diagnostic criteria, improve risk stratification beyond LDL-C and family history, guide treatment decisions, and improve treatment initiation and adherence 3.
• Molecular diagnosis is recommended but still not widely available and reimbursed 4.
• New clinical diagnostic criteria like FAMCAT are being tested and are apparently more accurate than the classical ones 4.

Benefits of Lipid Testing

The benefits of lipid testing for familial hypercholesterolemia include:

• Early identification and aggressive treatment of FH to minimize the risk for premature coronary heart disease (CHD) 5, 2.
• Improved risk stratification and guidance of treatment decisions 3.
• Identification of patients with homozygous FH or treatment-resistant FH who may require more aggressive treatment, such as LDL apheresis or novel therapeutic agents 5, 2.

Recommended Testing

Recommended testing for familial hypercholesterolemia includes:

• LDL-C levels 5, 2.
• Apolipoprotein B (APOB) levels 6.
• Genetic testing for mutations in the LDL receptor gene (LDLR) and other genes associated with FH 6, 3.
• Lipoprotein(a) concentrations 4.