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Archive for the ‘Cardiology -Mechnisms of disease’ 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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This cartoon succinctly  depict all the options we have in our fight against end stage heart failure .We know , a failing heart is often compared to a sick , aged and tired horse.

cardiac failure cartoon tired horse whicpping lionel opie book

Image courtesy Heart Physiology: From Cell to Circulation :Lionel H. Opie Lippincott Williams & Wilkins, 2004

 

1.Don’t whip the horse (Except in emergency)

  • Avoid all Inotropics ( Doubutamine and Milrinone were shown to improve quality of life marginally but  with dramatic reduction in quantity of life ! However , the same thing does not apply for Digoxin as it is the  the only Inotropic with a soothing para-sympathetic comfort  !
  • Please be reminded, CRT wires could act as  “multiple whip equivalents” right inside the heart , especially in advanced class 3 or just recovered class 4 patients. Beware!

2.Unload the horse

Vasodilators

  • ACEI/ARBS

3.Slow the horse

  • Never exert too much (Not more than 70% of capacity)
  • Beta blockers
  • Ivabradine (Slow the sinus node and expect a reduction in MVO2 )

4.Change the horse

  • Heart transplant may be the best solution

5.Switch to an Artificial Horse(Tractor )

  • ie  LV assist device

6.Finally try to heal the horse (Still largely in research labs!)

  • Genetic engineering
  • Tissue repairing
  • Stem cells
  • Holistic and spiritual healing etc (Has really  worked in few )

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When a patient comes with angina at rest , it could mean two things .Either a  STEMI or an NSTEMI .This , we can diagnose only after seeing the ECG .

Can we differentiate these two by the  character of chest pain alone ?

Very  tough task isn’t  ? But there are some definite clues .

Infarct  pain

  • Is mostly sudden .
  • Likely to be crescendo , lasts more than 20-30 minutes .
  • Fails to get relived by rest or even  Nitrites.
  • Sweating due to sympathetic activation is more pronounced.

Unstable angina

  • Is rarely  sudden .Often has a pro-drome.
  • UA is  mostly precipitated by an increased demand situation or a stress.
  • It has  a typical waxing and waning  pattern . Rarely assume a true  crescendo character  as myocytes  does not necrose (Just threaten to die !)
  • The chest pain radiation   to  shoulder is less  conspicuous , instead it  tends to  reach  the  jaw area .(* An observation,Is it something to do with multi-vessel CAD in UA ?)

Mechanism of the difference : Epicardial vs Endocardial angina

The pain of UA is   due to subtotal occlusion and  endocardial ischemia , while STEMI is  sudden total occlusion  and the resultant  transmural  ischemia . In STEMI  epicardial  surface is always involved (Which lifts the ST segment in ECG .).We know epicardium  is same as  visceral layer of pericardium which is well innervated .Hence  pain  of STEMI   acquires  more of somatic character  than a  predominately visceral type pain  that occurs with  UA/NSTEMI where epicardial ischemia is absent.

Clinical importance

The demarcation between unstable angina and Infarct pain becomes vital when we calculate the time window for thrombolysing STEMI .Many of them have a phase of pre infarction angina which is a type of unstable angina. If we mistake it for Infarct pain then one may falsely calculate a prolonged time window and deny re-perfusion therapy.

Post -amble

It is tricky issue  to differentiate the  chest pain of  STEMI and NSTEMI  .A significant overlap can occur  in  real coronary care scenario . We know   chest pain  that occurs in both   pre and post infarct  phase  is considered  as unstable angina .(With infarct pain sandwiched between them!) Hence differentiating  them may even be termed as futile.

Still,clinical cardiology  can be  made  fascinating by indulging in such exercise !

 

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We  traditionally believe  LV enlargement  results in dilatation of mitral annulus  from below  and  result in functional MR.
A lesser known  concept is , LA enlargement dilating the  mitral annulus from above and cause MR   !
Can atrial enlargement per se dilate mitral annulus ?

We often find  some degree of MR   associated with chronic  atrial fibrillation.What is the mechanism ?We also know MR begets MR.Is it because of progressive LV or LA enlargement ?

When the literature is searched  we have convincing proof that  LA enlargement can lead to significant  mitral annular dilatation and MR as well .
left atrial enlargement and mitral annuluseffect of la enlargement on mitral annulus
Reference

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critical decision making cardiology cath lab tricks coronary  angiogram primary angioplasty ptca vs cabg acc aha guidelines esc guidelines

Answer

While our brain perceives  whatever option  we  choose is the best for the patient  , in reality it is rarely true !

The only comment I wish to make,  there is nothing called standard guidelines for complex and unusual problems .We need not be obsessed with protocols  !

Please remember , If you apply standard guidelines  in  non-standard situations  9/10 times we  are going to err !

So my  choice  would be, to  go with your gut feeling , of course  your gut should  be alive ,  up to date and periodically maintained !

If you don’t have the guts  . . . don’t worry  you have plenty of other options !

 

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  • Diabetes , smoking , hypertension , dyslipidemia are the  leading cause of cardiac morbidity and  mortality .
  • Now air pollution the(  passive atmospheric smoking !) is threatening to be a major risk factor .
  • In fact , it has become the  official  cardiac risk factor nominated by WHO !
  • 40 %  of all deaths due to air pollution is due to cardiac events .
  • The surprise element is indoor air pollution is equally injurious .

WHO bulletin  in March 2014

air pollution and cardivascular health

The WHO assessment found the majority of air pollution deaths were linked with cardiovascular diseases.

For deaths related to outdoor pollution, it found:

  • 40% – heart disease
  • 40% – stroke
  • 11% – chronic obstructive pulmonary disease (COPD)
  • 6% – lung cancer
  • 3% – acute lower respiratory infections in children

For deaths related to Indoor pollution, it found:

  • 34% – stroke
  • 26% – heart disease

 

Related article from this site

A-new-coronary-risk-factor-community-smoking

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  • Diabetes mellitus is a pro-coagulant state,especially so in severe uncontrolled states.(1)
  • This is mediated by increased  levels of   plasminogen  activator Inhibitor.(PAI 1 and 2
  • This tilts  anti-fibrinolytic  forces towards thrombosis.
  • High PAI-1 is an Independent risk factor for MI in young individuals (3)
  • During STEMI the success rate of  fibrinolysis is significantly lower in diabetic population because high levels of PAI 1 .
  • The triad of DM,Obesity, Insulin resistance is a powerful predictor of  poor  response to thrombolysis.

 

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