Cholesterol - Lipids
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.
