Hyperlipidimia is one of the well-known coronary risk factor.Serum cholesterol ( Various fractions ) levels are measured to represent that risk. Epidemiologically ,it does a perfect job , however , the fact is , circulating lipids has little correlation with the lipids that’s deposited in the vessel wall.
Time and again , we have proven this as severity of CAD has little to do with the absolute levels of lipid levels.The number volume of plaques , the thickness of lipid core, and degree of vulnerability show poor correlation with circulating lipid levels than what we would expect.It tempts us to make a statement , that serum lipid is a poor surrogate marker for CAD. (Still, it may predict the risk of developing it !)
Why this paradox ? What are the missing links and hidden secrets ?
If you plot a simple graph with serum lipids with plaque mass, volume and content in CAD population , we might get an answer .I don’t know whether such a study exist. (Those who find one , please share)
A new concept called cholesterol crystalisation
It’s not the lipids alone that are responsible for CAD . There is a whole lot of factors , circulating pro inflammatory mediators, altered blood coagulation system , various inflammatory molecules, , heightened intra-coronary pressures, genetic vulnerabilities .
Most importantly ,the format of lipid molecule in side the plaque seems to matter more rather the absolute content.(Small dense LDL, oxidised lipids,Lipid fed macrophages etc )
There is lesser reported phenomenon called cholesterol crystalisation , with sharp edges (Lipid knife ?) that are responsible random episodes plaque fissure and rupture.
It was reported in one of the rare research paper that came from (Abela Am J Cardiol.2009) Factors that crysalise cholesterol include local saturation, PH, temperature , hydration and plaque RBC contact.
If you argue lipid levels are not correlating with CAD , how is that reducing it with statins dramatically reduce CAD and the events ?
Like blood pressure the normality of serum lipids itself is not defined.One insightful definition was proposed , that the level at which a person develops CAD is high for that patient however low it may be..A person who develops extensive CAD say at a level of 90mgLDL what to infer ? We do not know exact answer.
That’s why the concept of satin for all with clinical CAD looked attractive. Still , statin’s action doesn’t help answer the original query about the relationship between blood lipids and plaque lipids.
Statins beneficial effect is not by reduction of serum cholesterol.It primary acts by regressing intra-plaque lipids by blocking synthesis of lipids in every cell.The anti inflammatory,plaque stabilisation action of statin may be independent of lipid reduction.How much it contributes to overall benefits is not known.
The mystery will deepen
Not every LDL is bad.(I will be slapped if I call them Good LDL !) Small dense LDL , LDL P (Particle) ApoB (The real culprit on which LDL piggybacks ) lipoprotein little a and so many other lipid sub particles are being studied.
Final message
The purpose of this post is not to confuse our understanding about coronary lipidology but to widen our vision . Serum lipids remain a poor surrogate marker for plaque lipids. This is because , It’s rather a small fraction of sample volume we catch in the circulating blood , while loads of lipids gets deposited elsewhere in the body ! This also make it clear,no single risk factor in isolation is really CAD risky.It is the combination of risks , genetic susceptibility , LDL subfractions, few unknown risk/protective factors and finally a mandatory trigger(Hemodynamic, Emotional ?) that determine the outcome of CAD.
So ladies and gentle men , just don’t over react to mildly abnormal lipid levels you often find in master health checks .There is much more untold stories behind the true CAD risk than the glossy lab printouts would suggest !
Reference
2.
3.The Role of Lipids and Lipoproteins in Atherosclerosis MacRae F Linton, MD, Patricia G Yancey,
Dr.S.Venkatesan MD 