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Posts Tagged ‘hdl’

I’m trying to get  a right  answer for this question for quiet some time. The literature on lipids is so vast  , one can never finish reviewing it.There are   nearly two dozen journals that  deal with lipids ,Atherosclerosis, obesity ,and vascular biology .

Yet  , the answer to this simple question is elusive to us .The Irony is complete when we have evidence for   two diagonally  opposite responses 4 and 5 .

My interpretation of the issue

Any lipid molecule if exceeds a critical  level ( Only  if   . . . associated with hypertension, or diabetes or smoking ) can penetrate the vascular endothelium. ( HT-pressure injury , Smoke- Endothelial dysfunction  due to Nitric oxide depletion) DM -Glycation of cell membrane  , finally some  unknown inflammatory component )

Though evidence  for direct endothelial  injury is more for LDL ,  less for TGL (Almost nil  for VLDL , but  TGL has more VLDL in it !)

Strangely ,these molecules , express a mob psychological behavior .In isolation they appear innocuous. But ,in an  unfavorable   setting it shows signs of  revolt. If a group of  LDL molecule start attacking a  dysfunctional segment  of endothelium , the other molecules  like TGL and VLDL fractions would love to join the crowd  and inflict further  damage . (Of course ,the lonely HDL may watch the chaos silently !)

Questions to ponder

If LDL is a sharp knife like molecule  trying to injure the blood vessel , every normal human being is potentially threatened  by this  lipid fraction . Mind you,  this is a physiological molecule  traversing the human vascular system  at concentration  of 130mg/dl  at the  velocity of blood .

So it is  foolish  to blame this  physiological molecule for all our ignorance.

I recall one recent definition for hyperlipidemia

The lipid levels at which a patient develops vascular injury is considered high for him !

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Statins have revolutionised the treatment of coronary artery disease .Intensive lipid lowering is the fundamental prerequisite in the management of both acute and chronic coronary syndromes. One question  is  always difficult to answer , ( rather reluctant to find the answer )   “The effect of statins on the HDL cholesterol”. Logic and the mechanisms of action would suggest HDL is not much affected , but in reality  I believe , in a given patient statins  do  reduce the HDL by at-least 10-20 % .This might have some significance. However ,  the marked  reduction in LDL  may nullify the adverse effects of lowering HDL.   Does this happen in all

What does the scientific evidence say ?

It says the opposite .  It seems  HDL is raised by statins that too significantly . The following paper also  suggests mechanism of  HDL  elevation by statins .It is Independent  to that of LDL reduction , I believe .

This JAMA article  adds more evidence

http://jama.jamanetwork.com/data/Journals/JAMA/5100/jpc70001_499_508.pdf

This paper  from  the  premier  Journal  of   Lipid research  agrees  to the   mechanism of  HDL reduction by statin  is a complex process  but still  it vouches for it .

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035518/?report=printable

In spite of  all these  evidence . . .   it  remains a  huge suspect . . . from my personal point of  view ( My patients are  my evidence !  )

Coming soon

The above articles also raise an important  concept of dysfunctional HDL.  Simple raise  in HDL is not suffice . . .it should be functional as well !

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International Astronomical Union  in the year 2006  removed Pluto from the solar system for a simple reason ,  the so-called Pluto never revolved around  Sun , hence it ceased to be a planet of the solar system , it was more of an asteroid !

So, an astronomical fact engraved in our brains for so long  became a fairy tale. It is very hard  to erase  a  myth however solid the new evidence are against it.

The concept of HDL as good cholesterol has been etched deep in physician as well as our  patients.

Now comes the shocker from Lancet

How are we so sure ,  about these  Invisible spheres of  lipids that  move  around  our “Bio-system” in a presumed fashion .  .  .  even huge visible planets  fool us easily !

The Link to lancet study

It is  a wonderfully done study where  thousands of patients  who exhibited  genetically high HDL levels , never showed any advantage in terms of CAD prevention.  A stunning blow to a belief.

Incidentally ,  few years back  the failure of  drug Torcetrapib proved the same point  .  (The drug which elevates  HDL  proved useless in preventing CAD  ) but the  medical world failed to interpret it properly.

I am sure, still sections of physician  community would continue to believe HDL is great molecule for CAD protection !

Science is  often what we presume . . . but the fact usually turns out to be some thing  else !  but the journey towards truth  must continue !

                      When  a  million tonne  Pluto  suddenly disappear from Solar system . . . it is not a  big deal for  a  “miniscule medical myth”   to get shattered !

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Atherosclerosis   remains the number one cause for all vascular disease of human beings. It probably  kills more  patients than all other causes put together .

Modern medicine has never conquered the disease. How  the vascular system ages and why some develop premature atherosclerosis remains largely speculative. While it is true , we have identified some major risk factor for development and progression of the atherosclerosis  , patients with out any of those risk factors do develop severe atherosclerosis !So researchers sought to look for some other risk factors . There lies the difficulty  and irony .

We always tend to the research with the affected population .When we know millions of people with the so called risk factors live comfortably , there lies an opportunity  to  analyse why they are protected against the onslaught of atherosclerosis .It is always convenient to blame it or bless it on the genetic predisposition .But we need to look beyond that .Of course  . every genetic expression has to  manifest phenotypically .

While the search for all those hidden secrets has to continue , we should also realize in pursuit of breakthrough we some times waste our energy in false targets  for too many decades !

The reality as on today is ,  there is no reliable  &  undisputed drug available to arrest atherosclerosis  (Some would love to call statin so . . . )

While  our basic science colleagues struggle  in molecular  factories and biological models in pursuit of answer against  atherosclerosis , our elite  cardiac physicians   carry on with the cosmetic touches over this   progressive disease  in  sophisticated cath labs.

Let us hope  man prevails over nature . . .

A cartoon , Just for laughs . . .

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We know diabetes, smoking, hyperlidemia, hypertension are major risk factors for progressive vascular disease. They damage the vascular endothelium either directly or indirectly ,   by aggravating the atheroscelortic process .  Diabetes apart from affecting the medium sized arteries , also affect the microvasculature.  Smoking  has a direct effect on endothelial function .It depletes vascular nitric oxide. High levels of circulating lipids injures the sub endothelial structures and invades the media by entering macrophages .So , all these 4 risk factors either operate independently or interact with each other and result in progressive vascular    disease.

While we  believe  , these risk factors do not have any bias in attacking the human vascular  tree, in the real world it is observed they have their own  behavior pattern and  have unique predilection and a deadly alliance .

For example , in  chronic smokers TAO is the commonest manifestation , thrombo angitis is far too less common to occur in the coronary arteries.

Similarly  hypertension  per se  rarely results in an acute coronary syndrome while it is  the  single  important  cause for cerebro vascular  disease. Diabetes especially in women has very strong predilection for CAD , while diabetic per se is a lesser risk for stroke. Hyperlipedimia may be the one which has fairly even risk throughout the vasculature. Similarly there is  a difference in renal and   carotid arterial involvement with reference to  the conventional  risk factors .

SHT diabetes dyslipidemia coroanry risk factor

Why this apparent difference ?

We are unlikely  to get an answer to this question in the near future .  Left to the youngsters  . . . of tomorrow !

* Note of  clarification

The source for the above chart is collected from various studies and also a huge observational data from our hospital. There could be some geographical variation , a given individual may respond differently to these risk factor depending upon his genetic predisposition and susceptibility . So the above data can be applied to general population and not to a individual.

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10.14prescriptionRXStatins are projected to be  the saviours of human race against the  killer atherosclerosis .Now we have reached a stage  soon ,  where every healthy individual may be administered this drug. There are consistent evidence for statins to reduce , retard , prevent progression of existing atheroscelorosis  and possibly prevent future atherosclerosis.

This  wonder drug acts by blocking the HMG COA enzyme a vital  enzyme that regulates the lipid metabolism within the cells. It is made to appear  as if ,  the  God has  created this enzyme  with the only purpose for human suffering , by blocking this   we  expect  all errors in lipid  metabolism is corrected.

This enzyme is  part of the house keeping  system  that is meant to service the human cellular lipid layers 24hrs a day. If it  is impaired intentionally one can imagine the consequences. That’s what modern science is all about. Luckily God is kind enough the side effects of  blocking this enzyme is seen only in minority. The myopathies that are classically described with statins are due to possible mitochondrial dysfunction .

As the debate still  continues to find the   optimal bottom levels  of LDL  , we have more worries ,  real world experiences have brought us a new issue  namely  the  reduction of HDL with statins. While literature search on statins and HDL  tell  us there is marginal increase in HDL up to 10% the fact is there is marginal fall or significant  fall in many of the patients .

How can this happen ? A  huge difference between real world and trial world ?

statins hdl ldl

* Brands shown  not intentional

Readers are welcome to add their input on this question .

Reference

Visit HDL forum

http://www.hdlforum.org/

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