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Hypercholesterolemia also called high cholesterol, is the presence of high levels of cholesterol in the blood.
Definition:
LDL-cholesterol > 190 mg/dL, or > 160 mg/dL + 1 major risk factor, or > 130 mg/dL with 2 CVS risk factors:
- Age (♂ ≥ 45 years; ♀ ≥ 55 years)
- Family history of premature atherosclerotic cardiovascular disease
- Hypertension
- Diabetes
- Smoking
- Low HDL-cholesterol levels (♂ < 40 mg/dl; ♀ < 55 mg/dl)
Physiology

Aetiology
Genetic causes:
- Familial hypercholesterolemia (FH) (d/t defects in the LDL receptor (M/C), apolipoprotein B (ApoB), or proprotein convertase subtilisin/Kexin type 9 (PCSK9)
- Autosomal recessive hypercholesterolemia (d/t mutation in LDL receptor adaptor protein resulting in defective endocytosis of the LDL receptors)
Secondary causes:
- Hypothyroidism
- Nephrotic syndrome
- Cholestasis
- Pregnancy
- Drugs: Cyclosporine, thiazide, and diuretics
Clinical features
Although hypercholesterolemia itself is asymptomatic, longstanding elevation of serum cholesterol can lead to adverse cadiovascular complications.
Familial hypercholesterolemia (Type IIa hyperlipoproteinemia):
Features specific physical findings:
- Xanthelasma palpebrarum (yellowish patches underneath the skin around the eyelids)
- Arcus senilis (white or gray discoloration of the peripheral cornea)
- Xanthomata (deposition of yellowish cholesterol-rich material) of the tendons, especially of the fingers
Complications:
Hypercholesterolaemia is one of the major modifiable risk factors for atherosclerotic cardiovascular disease (CVD), a global health problem
- Heart Disease
- Stroke
- Peripheral vascular disease
Diagnosis
Plasma lipid profile:
Screening test recommended for all adults > 40 years, preferably after a 10-12-hour overnight fast
- Friedewald formula: LDL-C = Total Cholesterol – VLDL(TG/5) – HDL-C
Exclusion of secondary causes:
- TSH (hypothyroidism)
- Glucose (diabetes)
- Urinalysis
- Serum albumin (nephrotic syndrome)
- Bilirubin & alkaline phosphatase (cholestasis)
Management
Healthy lifestyle:
Cornerstone of treatment of hypercholesterolemia
- Optimum weight
- No smoking
- Exercising for 150min/week
- Dietary changes: Low saturated and trans-fatty acids and enriched in fiber, fruit, and vegetables and fatty fish
Medical management:
The decision to go beyond dietary advice and introduce lipid-lowering medication is based on an assessment of risk so that treatment is deployed in those who will benefit the most
- Statins (first-line drugs)
- Cholesterol absorption inhibitors (ezetimibe) and/or bile acid sequestrants (next-line drugs)