Familial Hypercholesterolemia: Global Burden and Approaches

Area of Science:

• Genetics
• Metabolic Disorders
• Cardiovascular Medicine

Background:

• Familial hypercholesterolemia (FH) is the most prevalent genetic metabolic disorder.
• It is characterized by elevated LDL-C levels from birth, leading to premature atherosclerotic cardiovascular disease (ASCVD) and mortality.
• Despite its prevalence (1/200-250), FH is significantly underdiagnosed and undertreated globally.

Purpose of the Study:

• To review current knowledge on FH diagnosis, risk estimation, and management.
• To incorporate recent evidence and guideline recommendations.
• To emphasize the need for early identification and intervention.

Main Methods:

• Review of recent registries and genetic studies.
• Analysis of diagnostic criteria (e.g., Dutch Lipid Clinic Network).
• Evaluation of risk stratification tools (e.g., coronary calcium scoring).
• Assessment of current and novel therapeutic agents.

Main Results:

• FH is caused by mutations in genes like LDLR, APOB, PCSK9, and LDLRAP1.
• Clinical diagnostic scores and genetic testing aid identification.
• Risk is influenced by traditional factors and lipoprotein(a).
• Effective LDL-C lowering is achievable with statins, ezetimibe, PCSK9 inhibitors, apheresis, and newer agents like bempedoic acid, inclisiran, and evinacumab.

Conclusions:

• Early diagnosis and initiation of LDL-C lowering are essential for reducing ASCVD morbidity and mortality in FH patients.
• Increased awareness among healthcare professionals, patients, and the public is critical for improving diagnosis and treatment rates.
• Despite therapeutic advances, FH remains a significant public health challenge requiring greater attention and proactive management.