hypercholesterolemie

Hypercholesterolemie, also known as hypercholesterolemia, is a medical condition characterized by persistently elevated cholesterol levels in the blood, most notably low-density lipoprotein (LDL) cholesterol. Elevated LDL-C contributes to the development of atherosclerosis and increases the risk of coronary heart disease and stroke.

There are two main categories: primary (genetic) and secondary (acquired). Primary forms include familial hypercholesterolemia, usually inherited in an autosomal dominant manner, caused by mutations in LDLR, APOB, or PCSK9. Heterozygous FH affects about 1 in 200–250 people; homozygous FH is rarer and causes very high LDL-C from birth. Polygenic hypercholesterolemia arises from multiple small-effect genetic variants. Secondary causes include hypothyroidism, nephrotic syndrome, liver disease, certain medications, diabetes, obesity, and dietary factors.

Diagnosis is based on lipid measurements. A fasting lipid panel showing elevated LDL-C (for example, ≥190 mg/dL or >4.9 mmol/L) raises suspicion of primary forms. Confirmation may involve family history, physical signs such as xanthomas or corneal arcus, and formal diagnostic criteria (e.g., Dutch Lipid Clinic Network, Simon Broome).

Clinical presentation: many individuals have no symptoms; signs may include tendon xanthomas, xanthelasmas, or corneal arcus. The condition increases lifetime risk of atherosclerotic cardiovascular disease, especially at a young age.

Management: lifestyle measures (heart-healthy diet, physical activity, weight control) and pharmacotherapy to lower LDL-C. First-line treatment is high-intensity statin therapy; ezetimibe is added if goals are not met. For some patients, PCSK9 inhibitors, bempedoic acid, or inclisiran may be used. In homozygous FH, lipoprotein apheresis or novel therapies may be required.

Screening and prognosis: cascade screening of first-degree relatives is recommended when FH is suspected. With appropriate treatment, cardiovascular risk can be substantially reduced, though residual risk remains.

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