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Lipids & Atherosclerosis

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Definitions and Basics

  • cholesterol is hydrophobic - not soluble in water (or blood plasma)
  • cannot be traveling in bloodstream as a standalone fat - needs a "carrier" protein
These are called lipoproteins, and there are numerous types with differing characteristics
  • chylomicrons (from intestine)
  • VLDL - chylos and VLDLs clear quickly unless you have remnant issues (ApoC)
  • LDL - classically the most atherosclegenic particle, does't clear for days.
  • HDL - Apo(A) protein, rest are Apo(B)
  • the purpose of Lipoproteins is NOT to transport cholesterol
    • cholesterol can be manufactured by almost all cells that need it
    • transfer phospholipids and triglycerides for energy
  • so you can get your cholesterol numbers in blood way way down and cellular level is totally fine
  • if there is too much cholesterol (too many LP particles), they can stick to artery walls and cause plaque and heart disease

Why measure APoB?

Background

  • The default LDL measure is amount of cholesterol in a liter of blood. This is often, but not always, correlated with the NUMBER of lipoproteins in the blood because the lipoproteins can be different sizes
  • we know from biochemistry and physically how the blood vessels and particles are structured that it is the lipoprotein cholesterol that is lodging itself into artery walls and calcifying
  • we also know the mechanism (link) and its the AMOUNT of particles, not the amount of cholesterol, that ultimately correlates

ApoB

  • protein "shell" in many of the lipoproteins (not HDL) . LPs are constantly shedding and acquiring proteins and lipids, but ApoB never really moves, only one per molecule
  • VLDLs, chylomicrons, LDLs, IDLs have it. Only LDL half life in blood stream is long enough (3-5) days to matter - so 95% of ApoB particle measurement will be LDL

HDL

reverse cholesterol transport we simply don’t know, no biomarkers. HDL could be low because they are so effective, or so high because they cant delipase at liver

snapshot when you need a video, flux vs stasis

HdL carry a ton of proteins are very complicated

  • this does NOT mean HDL is "good". first of all need particle count but even then you dont know how it's all interacting to get cholesterol back to liver
  • HDL could bring to intestines or liver. HDL could handoff to LDL.

Drugs

  • Statins are the big guns: use mega doses to stop production of cholesterol. this means your particles must be cleared much faster to provide cholesterol to cells
    • But brain needs cholesterol, so this can cause cognitive decline
  • Dayspring prefers baby statin dose with Zedemibe
  • Zedemibe stops absorbtions of cholesterol in gut and intestines
    • this combo can reduce apoB just as much as gorilla statin
  • Newest most expensive drugs: PCSK9. Works by extending life of LDL receptors on liver, more cholesterol absorbed.
  • Niacin - Dayspring hates, thinks it is reducing apoB but also doing something bad. dose is crazy high
  • Fibrates break down fats for absorbtion
  • Statins block natural production of cholesterol so that body uptakes blood cholesterol