Makindo Medical Notes

Cholesterol is a vital lipid molecule essential for cell structure, hormone synthesis, and bile acid production. While it is crucial for health, excess levels—especially of LDL cholesterol—are a major risk factor for atherosclerosis and cardiovascular disease.

🔬 Role and Functions of Cholesterol

• Cell Membrane Structure: Maintains stability and fluidity of membranes, regulating permeability and signalling.
• Steroid Hormones: Precursor for cortisol, aldosterone, progesterone, oestrogens, and testosterone.
• Bile Acids: Enables digestion and absorption of dietary fats.
• Vitamin D: Synthesised from cholesterol in the skin under UV light.

🧩 Cholesterol-Derived Molecules

• Vitamin D
• Steroid hormones (cortisol, aldosterone, progesterone, oestrogens, testosterone)
• Bile acids

⚙️ Synthesis of Cholesterol

• Mainly occurs in the liver via the mevalonate pathway.
• Key step: HMG-CoA → mevalonate (enzyme: HMG-CoA reductase).
• This step is irreversible and is inhibited by statins.

❤️ Cholesterol and Atherosclerosis

• Raised LDL-C, IDL, and VLDL are atherogenic → plaque formation in arteries.
• Low HDL-C increases risk of cardiovascular disease.
• Total cholesterol = LDL + HDL + VLDL.

📊 Cholesterol Levels and Health

• High cholesterol: ↑ risk of MI, stroke, peripheral vascular disease.
• Low cholesterol: Associations with other conditions (e.g. cancer, haemorrhagic stroke) are inconsistent and less clinically significant.

💊 Statins and Cholesterol Lowering

• Statins inhibit HMG-CoA reductase → ↓ LDL synthesis in the liver.
• Proven to reduce cardiovascular morbidity and mortality.
• Target LDL levels:
  • General population: <100 mg/dL (<2.6 mmol/L)
  • High-risk (e.g. CAD, diabetes): <70 mg/dL (<1.8 mmol/L)

🧪 Measuring Cholesterol

• Measured by fasting lipid profile (12-hour fast).
• Includes: total cholesterol, triglycerides, HDL-C.
• LDL-C calculation: Friedewald formula → LDL = Total – HDL – (Triglycerides ÷ 5) (mg/dL).
  Note: invalid if triglycerides >400 mg/dL (4.5 mmol/L).
• Levels may fall during acute illness (beware underestimation).

🎯 Target Levels (UK Guidance)

• High-risk patients:
  • Total cholesterol: <4 mmol/L (<155 mg/dL)
  • LDL-C: <2 mmol/L (<77 mg/dL)
• Very high-risk (established CVD): aim even lower if tolerated.

✅ Conclusion

Cholesterol is essential for physiology, but imbalances drive cardiovascular risk. Measuring lipid profiles, identifying high-risk patients, and initiating statin therapy when indicated remain cornerstones of prevention. ⚡ Remember: lowering LDL saves lives, and targets should be tailored to overall risk profile.