Hyperkolesterolemia

Hyperkolesterolemia is a condition characterized by persistently elevated levels of cholesterol in the blood, most notably low-density lipoprotein cholesterol (LDL-C). It increases the risk of atherosclerotic cardiovascular disease (ASCVD) and related complications. The condition can be primary (genetic or polygenic) or secondary to other medical conditions or medications.

Primary hyperkolesterolemia includes familial hypercholesterolemia (FH), caused by mutations affecting LDL receptors, apolipoprotein B, or PCSK9, which leads to high LDL-C from birth. FH can be heterozygous or homozygous and is associated with premature ASCVD. Polygenic hypercholesterolemia results from the cumulative effect of multiple common genetic variants that raise LDL-C modestly. Secondary causes include hypothyroidism, nephrotic syndrome, liver disease, uncontrolled diabetes, obesity, and certain drugs; these can raise cholesterol levels in addition to genetic factors.

Diagnosis typically relies on a lipid panel showing elevated LDL-C, often with elevated total cholesterol and sometimes elevated triglycerides. Non-HDL cholesterol is also used. FH suspicion may be based on very high LDL-C from a young age, family history of premature ASCVD, and physical signs such as tendon xanthomas or corneal arcus; genetic testing can confirm the diagnosis. Screening first-degree relatives is commonly recommended.

Management focuses on reducing ASCVD risk. Lifestyle changes—heart-healthy diet, regular physical activity, weight management, and smoking cessation—are foundational. Pharmacotherapy to lower LDL-C is central: statins are first-line, with ezetimibe, PCSK9 inhibitors, and bile acid sequestrants as add-ons. Other options include bempedoic acid and, for certain forms, lomitapide. Regular lipid monitoring and liver enzyme checks guide ongoing care.