How Can We Identify Very High-Risk Heterozygous Familial Hypercholesterolemia?

Area of Science:

• Cardiology
• Genetics
• Biochemistry

Background:

• Heterozygous familial hypercholesterolemia (HeFH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol.
• This condition significantly increases the risk of premature atherosclerotic cardiovascular disease (ASCVD).
• Individual cardiovascular risk within HeFH populations varies considerably despite similar lipid profiles, necessitating refined risk stratification.

Purpose of the Study:

• To review and discuss potential approaches for improved cardiovascular risk stratification in patients with HeFH.
• To highlight the need for personalized therapeutic management based on individual risk assessment.
• To explore the utility of risk scores, genetic analysis, and biomarkers in managing HeFH.

Main Methods:

• Review of current literature and proposed risk stratification strategies for HeFH.
• Examination of the International Atherosclerosis Society's definition of severe FH.
• Analysis of studies linking FH-related genetic phenotypes and biomarkers to ASCVD risk.

Main Results:

• The International Atherosclerosis Society has proposed a definition for severe FH to identify high-risk individuals.
• Genetic analysis shows potential for evaluating individual cardiovascular risks in HeFH by correlating FH-related genetic phenotypes with ASCVD.
• Biomarkers reflecting disease activity may predict atherosclerosis development and ASCVD occurrence in HeFH patients.

Conclusions:

• Improved risk stratification for HeFH is crucial for optimizing therapeutic management and cardiovascular outcomes.
• Integrating risk scores, genetic analysis, and biomarkers can enhance the identification of high-risk HeFH individuals.
• Personalized risk assessment will enable tailored lipid-lowering therapies, ultimately improving patient prognosis.