Familial hypercholesterolemia and its manifestations: Practical considerations for general practitioners

Area of Science:

• Lipid Metabolism Disorders
• Cardiovascular Disease Genetics
• Pharmacology

Background:

• Familial hypercholesterolemia (FH) is a prevalent genetic disorder affecting lipid metabolism, occurring in approximately 1 in 250 individuals globally.
• Characterized by elevated LDL-cholesterol from childhood, FH substantially elevates the risk of premature atherosclerotic cardiovascular disease (ASCVD), including coronary heart disease (CHD).
• Despite its prevalence and associated risks, FH remains underdiagnosed and undertreated, necessitating improved diagnostic and therapeutic strategies.

Approach:

• This narrative review focuses on practical diagnostic and therapeutic considerations for managing Familial hypercholesterolemia.
• Emphasizes clinical criteria, including patient history, family history, clinical signs, and untreated LDL-C levels, for prompt FH diagnosis.
• Discusses the management of associated non-CHD morbidities like stroke and peripheral artery disease.

Key Points:

• Statins are the primary treatment for FH in adults and children over 8.
• For statin-intolerant patients or those not reaching LDL-C targets, ezetimibe and PCSK9 inhibitors are valuable options.
• Newer medications like inclisiran and bempedoic acid offer expanded therapeutic choices for FH management.

Conclusions:

• Prompt diagnosis and intervention are essential to mitigate the high ASCVD risk in FH patients.
• A multi-faceted treatment approach, including lifestyle modifications and pharmacotherapy, is key to managing FH.
• The evolving therapeutic landscape provides enhanced options for optimizing LDL-C reduction and patient outcomes in FH.