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Archive for the ‘hyperlipidemia’ Category

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, 

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One big hypertension trial called SPRINT was published in 2015, has caused major delayed aftershocks in the hypertensive world now in 2017.

The new guidelines by 2017  AHA/ACC is based primarily on SPRINT data which in my opinion has so much flaws it shouldn’t have been accepted for publication in the first place. !(Intentions and Aim of a study can never be questioned even by most prestigious journals you know !)

  • The flaws begin right  from study design itself. Why diabetic population was excluded from the SPRINT trial is not clearly answered in the true interest of public.The Ironical argument is diabetic patients had no benefit with intensive BP management in ACCORD study. So why waste another study ! Funny is in’t? 
  • When CVD risk profile is intimately linked with these two major entities (DM/HT) it defies sense to  exclude  one them from the study, which is going to assess population based total  CVD risk reduction.
  • Another dramatic confounder is , 90% of SPRINT patients were taking baseline anti HT drugs. So, the original pressure of these people (No,they are patients really !) should have been high . (If you apply this logic , SPRINT study conclusions will not apply for general population who are healthy and free from drug intake! )
  • SPRINT trial also concluded there is little benefit in acute MI and renal protection. The main benefit that tilted in favor of SPRINT was preventing episodes of cardiac failure which was defined by the primitive , subjective , ever unreliable symptomatology of exertional dyspnea.

The ultimate spoiler in SPRINT 

The modality of BP measurement in SPRINT trial can be  termed as as single fit case for rejecting the study in the world hemodynamic court !

We know BP is a continuous variable, between machines , timing of measurement, persons who measure , hand to hand , beat to beat variation etc etc. The SPRINT BP data was accrued  high-profile “Research standard BP” measured by oscillometry method. Please hold your breath , . . these  machines never measure either systolic or diastolic BP.It detects the peak oscillations from brachial artery when the cuff is deflated and ask the vendor dependent fuzzy logic  algorithm to do a guess work of  SBP and DBP , which  proudly flashes them in various LED colors.

The jury is still out whether the methodology is validated or not. SPRINT data should be thoroughly sanitized with a true clinic BP which would  virtually  mean , recall of this (de) famed study !

Final message

How can such a flawed study be taken as reference for  creating major revision of  Hypertension guidelines? 

This question is to be asked in chorus by all respectable physicians and cardiologists.The World health organisation -WHO , custodian of  human health and the silent watch “puppy” has more work to do ! . . please WHO , wake up and bark !

Reference 

1.A Randomized Trial of Intensive versus Standard Blood-Pressure Control The SPRINT Research Group  N Engl J Med 2015; 373:2103-2116 

2.http://www.acc.org/latest-in-cardiology/articles/2015/12/01/10/04/the-sprint-trial-cons

3.http://www.cardiobrief.org/2017/02/08/new-questions-raised-about-sprint/

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