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Familial Hypercholesterolemia: Still an Enigma
Sahej Arora1, Adnan Kharsa2, Gaurav Sharma2
1Department of Internal Medicine, Rochester General Hospital, Rochester, New York, USA.
JACC. Case Reports
|August 29, 2025
Summary
Familial hypercholesterolemia (FH) is a genetic disorder causing high LDL cholesterol. Remarkably, some patients with FH may not develop atherosclerosis, suggesting protective factors influencing lipid metabolism.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Metabolic Disorders
Background:
- Familial hypercholesterolemia (FH) is an inherited condition.
- Characterized by significantly elevated low-density lipoprotein (LDL) cholesterol levels.
- Associated with premature atherosclerotic cardiovascular disease.
Observation:
- A 61-year-old woman with a decade-long history of LDL >200 mg/dL was diagnosed with FH.
- She carried a pathogenic LDLR mutation.
- Risk stratification revealed no evidence of atherosclerotic disease via coronary CT angiography or carotid ultrasound.
Findings:
- Despite lifelong severe hypercholesterolemia and a pathogenic LDLR mutation, the patient showed no signs of atherosclerosis.
- Coronary artery calcifications typically appear early in FH patients (11-23 years).
- The absence of cardiovascular disease and family history suggested a potential protective factor in her LDL metabolism.
Implications:
- Heterozygous FH patients can remain free of atherosclerosis.
- This case highlights potential protective mechanisms against hyperlipidemia-induced cardiovascular disease.
- Further research into these protective factors could offer novel therapeutic targets for FH.
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