LDL Molecular Composition

1. Lipids:
   • Cholesterol (Free and Esterified): The core contains cholesteryl esters (cholesterol bound to fatty acids), making up ~40-50% of LDL’s mass, and some free (unesterified) cholesterol on the surface. Cholesterol is used for cell membrane synthesis and hormone production.
   • Triglycerides: A smaller portion (~5-10%) of the core, these are fats used for energy or storage.
   • Phospholipids: Form part of the outer shell (~20-25%), providing structural stability and solubility in blood.
2. Apolipoproteins:
   • Apolipoprotein B-100 (ApoB-100): A single, large protein on the LDL surface (~20-25% of mass) that stabilizes the particle and binds to LDL receptors on cells, facilitating cholesterol delivery.
     Each LDL particle has one ApoB-100 molecule, making it a key marker for LDL particle number.
3. Minor Components:
   • Small amounts of other molecules, like fat-soluble vitamins (e.g., vitamin E) or antioxidants, may be present but play a minor role.

Which LDL Components Are Risky?
The risk associated with LDL primarily stems from its role in delivering cholesterol to tissues and its potential to contribute to atherosclerosis when levels are high. Specific risky aspects include:

1. Cholesterol (Particularly Cholesteryl Esters):
   • Why Risky?:
     Excess LDL cholesterol, especially cholesteryl esters, can deposit in arterial walls, forming plaques that lead to atherosclerosis, increasing the risk of heart attack, stroke, and peripheral artery disease. High LDL cholesterol levels (typically >100 mg/dL, depending on guidelines) are considered a major cardiovascular risk factor.
   • The cholesterol in LDL is not inherently “bad,” but when LDL particles are too numerous or modified (e.g., oxidized), they promote inflammation and plaque buildup.
2. Apolipoprotein B-100 (ApoB-100):
   • Why Risky?:
     ApoB-100 is a marker of LDL particle number. A higher number of LDL particles (measured by ApoB levels) increases cardiovascular risk, even if total cholesterol appears normal. Small, dense LDL particles, which have higher ApoB relative to cholesterol content, are particularly atherogenic because they penetrate arterial walls more easily.
   • ApoB testing is increasingly used to assess risk more accurately than LDL cholesterol alone, especially in patients with normal LDL but high triglycerides or metabolic syndrome.
3. Modified LDL (e.g., Oxidized LDL):
   • Why Risky?: When LDL particles are oxidized by free radicals, they become more inflammatory, triggering immune responses that accelerate plaque formation. Oxidized LDL is not a distinct molecule but a modified form of LDL’s cholesterol and protein components.
   •  Oxidative stress (from smoking, excessive exercise, poor diet, or diabetes) increases this risk, making LDL more dangerous.

LDL’s risks can be connected to Lp(a), as Lp(a) is structurally similar to LDL, containing ApoB-100 and cholesterol, but with an additional apolipoprotein(a) that heightens its atherogenic and prothrombotic potential.
High LDL cholesterol and ApoB levels, like high Lp(a), are genetically influenced and key risk factors for cardiovascular disease.
While statins lower LDL cholesterol, they don’t significantly reduce Lp(a), making Lp(a) a unique risk factor.
Key Takeaway: High LDL cholesterol and ApoB-100 levels increase the risk of atherosclerosis by delivering excess cholesterol to the arteries.
Small, dense LDL particles and oxidized LDL are particularly harmful.
Monitoring and managing LDL levels (via diet, exercise, or medications) is critical for heart health, alongside understanding the distinct risks associated with Lp(a).