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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.
Insights
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.
Background:
Familial hypercholesterolemia (FH) is a genetic condition characterized by high levels of low-density lipoprotein (LDL) and early atherosclerotic cardiovascular disease.
Case Summary:
Our patient was a 61-year-old woman who had been referred to a cardiologist for LDL levels >200 mg/dL for more than a decade. She tested positive for a pathogenic LDLR mutation and was diagnosed with FH. She then underwent risk stratification with coronary computed tomography angiography and ultrasound of the carotid arteries, both of which showed no atherosclerotic disease. She continues to do well off statins.
Discussion:
Coronary artery calcifications can be seen as early as 11 to 23 years of age in patients with FH. Our patient did not have any evidence of atherosclerotic disease, nor did she have a family history of cardiovascular disease, and it was thought that she may have a protective factor affecting LDL metabolism.
Take-Home Message:
Patients with heterozygous FH can have absence of atherosclerosis despite lifelong severely elevated LDL levels.
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