Hypercholesterolemia

Hypercholesterolemia refers to elevated levels of cholesterol in the blood, most notably low-density lipoprotein (LDL) cholesterol. It can be primary, often genetic, or secondary, arising from other conditions or lifestyle factors. Untreated hypercholesterolemia is a major risk factor for atherosclerotic cardiovascular disease, including heart attack and stroke.

Primary forms include familial hypercholesterolemia, caused by genetic mutations that impair the body's ability to clear LDL from the blood. Secondary hypercholesterolemia can occur with hypothyroidism, nephrotic syndrome, liver disease, diabetes, obesity, excessive alcohol intake, and certain medications. Excess LDL cholesterol promotes the formation of atherosclerotic plaques in arteries, leading to narrowing and reduced blood flow.

Diagnosis is based on a fasting lipid panel that measures total cholesterol, LDL-C, high-density lipoprotein (HDL) cholesterol, and triglycerides. LDL-C thresholds guide risk assessment: LDL-C levels above 190 mg/dL are often suggestive of familial hypercholesterolemia, while other patients are managed according to overall cardiovascular risk using additional targets such as non-HDL cholesterol. Screening is generally recommended in adults at least every 4 to 6 years, with earlier and family-based screening for suspected familial forms.

Management emphasizes lifestyle changes and, when needed, pharmacotherapy. Lifestyle measures include a heart-healthy diet low in saturated fat and trans fats, regular physical activity, weight management, and smoking cessation. First-line pharmacologic therapy is statins. If goals are not reached or statins are not tolerated, additional options include ezetimibe, PCSK9 inhibitors, bempedoic acid, or bile acid sequestrants. In familial hypercholesterolemia, more intensive treatment and family screening are common.

Prognosis improves substantially with appropriate management, though hypercholesterolemia remains a persistent cardiovascular risk factor that requires ongoing care.