Comorbidities and Molecular Genetics Status in Familial and Nonfamilial Hypercholesterolemia: A Single-Center Study

Area of Science:

• Cardiology
• Clinical Genetics
• Internal Medicine

Background:

• Familial hypercholesterolemia (FH) is an inherited disorder leading to high cholesterol levels.
• Understanding comorbidities and genetic status in FH versus non-FH patients is crucial for effective management.
• Previous studies have highlighted the cardiovascular risks associated with FH.

Purpose of the Study:

• To compare the prevalence of comorbidities between patients with familial hypercholesterolemia (FH) and non-familial hypercholesterolemia (non-FH).
• To characterize the molecular genetic status in patients diagnosed with FH and non-FH.
• To evaluate the diagnostic yield of genetic testing across different FH probability categories.

Main Methods:

• A cross-sectional observational study involving 323 patients.
• Data collection included personal/family histories, physical exams, fasting lipid profiles, and molecular genetic testing.
• Patients were categorized into definite, probable, possible FH, and non-FH groups.

Main Results:

• FH patients exhibited a lower prevalence of cardiometabolic diseases compared to non-FH patients, who had a high rate of chronic pancreatitis.
• Coronary heart disease and peripheral atherosclerosis were more prevalent in probable/definite FH groups; myocardial infarction occurred across all groups.
• Pathogenic variants were identified in 78.2% (definite FH) and 71.4% (probable FH), primarily in LDLR and APOB genes. Possible FH showed a 46.7% variant detection rate.

Conclusions:

• Familial hypercholesterolemia (FH) is associated with fewer cardiometabolic comorbidities than non-FH.
• Molecular genetic testing has a high diagnostic yield, particularly in possible FH cases (Clinic Network score 3-5).
• Expanding genetic testing indications to include possible FH patients is recommended for improved diagnosis and care.