Cholesterol (high)

High Cholesterol (Hypercholesterolemia)

High cholesterol, also known as hypercholesterolemia, is a common metabolic condition characterized by elevated levels of cholesterol and other lipids in the blood. Cholesterol is a waxy, fat-like substance essential for normal cell membrane structure, hormone synthesis, and bile acid production. However, excessive levels, particularly of low-density lipoprotein (LDL) cholesterol, increase the risk of atherosclerosis and subsequent cardiovascular diseases (CVD) such as coronary artery disease, stroke, and peripheral vascular disease.

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Types of Cholesterol

• Low-Density Lipoprotein (LDL) – “Bad” Cholesterol
  LDL carries cholesterol to tissues. Excess LDL leads to plaque formation in arteries.

• High-Density Lipoprotein (HDL) – “Good” Cholesterol
  HDL transports cholesterol away from tissues and arteries back to the liver for excretion. Higher HDL levels are protective.

• Very Low-Density Lipoprotein (VLDL)
  Carries triglycerides and contributes to plaque buildup.

• Triglycerides
  Elevated triglycerides often accompany high LDL and low HDL, further increasing cardiovascular risk.

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Causes and Risk Factors

• Primary (genetic):

  • Familial hypercholesterolemia due to mutations affecting LDL receptor function.

• Secondary (acquired):

  • Unhealthy diet (high in saturated fats, trans fats, cholesterol).

  • Obesity and physical inactivity.

  • Type 2 diabetes and insulin resistance.

  • Hypothyroidism.

  • Chronic kidney disease.

  • Liver disease (e.g., cholestasis).

  • Alcohol overuse.

  • Certain medications (e.g., corticosteroids, diuretics, antiretrovirals).

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Symptoms

High cholesterol itself usually causes no symptoms. It is often detected through blood tests. Long-term uncontrolled cholesterol can lead to:

• Xanthomas (cholesterol deposits in tendons/skin).

• Corneal arcus (cholesterol ring around cornea).

• Symptoms of cardiovascular disease (chest pain, leg pain, stroke).

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Diagnosis

• Lipid Profile Blood Test (fasting or non-fasting):

  • Total cholesterol: Optimal < 200 mg/dL (< 5.2 mmol/L).

  • LDL cholesterol: Optimal < 100 mg/dL (< 2.6 mmol/L).

  • HDL cholesterol: Low < 40 mg/dL in men, < 50 mg/dL in women.

  • Triglycerides: Normal < 150 mg/dL (< 1.7 mmol/L).

• Risk Assessment Tools:

  • QRISK, Framingham risk score, ASCVD calculator used to estimate 10-year cardiovascular risk and guide treatment decisions.

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Complications

• Coronary artery disease → angina, myocardial infarction.

• Ischemic stroke and transient ischemic attack (TIA).

• Peripheral artery disease.

• Aneurysm formation due to arterial wall weakening.

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Management

1. Lifestyle Modifications

First-line intervention for all patients, regardless of baseline lipid levels.

• Dietary Changes:

  • Reduce saturated fats and eliminate trans fats.

  • Increase intake of omega-3 fatty acids (fish, flaxseed).

  • Increase dietary fiber (fruits, vegetables, oats).

  • Use plant sterols and stanols.

• Weight Management:

  • Even modest weight loss improves lipid levels.

• Exercise:

  • At least 150 minutes per week of moderate aerobic activity.

• Smoking Cessation:

  • Improves HDL and reduces CVD risk.

• Limit Alcohol:

  • Excess intake increases triglycerides.

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2. Pharmacological Treatment

Used when lifestyle measures are insufficient or when cardiovascular risk is high.

• Statins (HMG-CoA reductase inhibitors)
  First-line therapy for lowering LDL cholesterol.

  • Atorvastatin: 10–80 mg once daily.

  • Simvastatin: 10–40 mg once daily.

  • Rosuvastatin: 5–40 mg once daily.

  • Pravastatin: 10–40 mg once daily.

• Ezetimibe
  Cholesterol absorption inhibitor, used alone or with statins.

  • Dose: 10 mg once daily.

• PCSK9 Inhibitors (alirocumab, evolocumab)
  Monoclonal antibodies that increase LDL receptor recycling.

  • Alirocumab: 75–150 mg subcutaneous injection every 2 weeks.

  • Evolocumab: 140 mg subcutaneous every 2 weeks or 420 mg monthly.

• Bile Acid Sequestrants (cholestyramine, colesevelam)
  Bind bile acids, reducing cholesterol absorption.

  • Cholestyramine: 4–16 g/day in divided doses.

  • Colesevelam: 3.75 g/day.

• Fibrates (gemfibrozil, fenofibrate)
  Primarily reduce triglycerides and modestly increase HDL.

  • Gemfibrozil: 600 mg twice daily.

  • Fenofibrate: 145 mg once daily.

• Nicotinic Acid (Niacin)
  Increases HDL and lowers triglycerides, but use is limited by flushing and liver toxicity.

  • Dose: 500–2000 mg daily.

• Omega-3 Fatty Acids (EPA, DHA)
  Effective in lowering triglycerides.

  • Dose: 2–4 g/day.

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Monitoring

• Lipid profile checked 4–12 weeks after starting therapy, then every 3–12 months.

• Monitor liver enzymes with statins.

• Assess for muscle pain (risk of statin-induced myopathy).

• Evaluate cardiovascular risk periodically.

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Prognosis

With effective treatment and lifestyle modification, cholesterol levels can be normalized, significantly reducing the risk of cardiovascular events. Untreated hypercholesterolemia markedly increases morbidity and mortality from heart disease and stroke.