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Posts Tagged ‘biomarkers for pulmonary hypertension’

Uric acid is a  metabolite of purine metabolism.Purine is dynamically present in  every  active multiplying cell .Uric acid is formed when Xanthine oxidase  acts on   Xanthine and hypoxanthine  which are products of purine . The estimation of serum uric acid level can give us a rough estimate of cell metabolism and turn over. We need to  understand there is a dietary source for purines as well.

UA is mainly  excreted in urine . Normal levels of UA is   3-6mg in women and can be 1 mg higher  in men

Biological actions of uric acid

UA is a physiological molecule . It is more of an byproduct  and  devoid of any unique  action. Hence , most physicians still   believe it to be an unwanted  dangerous toxic molecule. What we fail to realise is ,  uric acid is a strong natural reducing agent .Hence it acts as an antioxidant .(Comparable to Ascorbic acid Vit C !)

Some believe excess uric acid is  a natural metabolic weapon against cellular degeneration . In fact , hypo- urecemia has a well known  association with multiple sclerosis and augmenting UA  is known to improve multiple sclerosis.

However, the problem with this  physiological molecule  is ,  we do not know yet,  when the  levels become pathological .We know uric acid in excess can lead to  urate stones  in kidney and Gout in joint . Does these crystals have any effect on coronary and cerebral circulation ?

Is uric acid a marker of inflammation and cell turn over ?

Yes it is.  What ESR  means to  inflammation , uric acid means for cell turnover . Since Inflammation induces white cell turnover  uric acid  level  becomes   a marker of inflammation as well .

Uric acid in  excess  is a  marker of vascular  damage as  atherosclerosis  is an inflammatory process  , especially  with  pulmonary endothelial damage. So , in patients  with primary pulmonary  vascular diseases  like PPH , uric acid levels   may indicate  the progression or regression of PAH.

Some studies have correlated right atrial pressure with uric acid levels.

Uric acid and hypoxic states

Uric acid formation is more in hypoxic states as hypoxia depletes ATP and adenine metabolism is promoted and more inosine and  Xanthines  are produced . Uric acid can be a simple  marker  of increased oxidation stress of human biological system.

No surprise  to note   pulmonary hypertension  an important hypoxic state  increase uric acid levels .

Why uric acid is rarely considered as a useful diagnostic marker in cardiology  ?

  • The major  reason is it is an old molecule and has  lost its  flavor .
  • The name is not exotic (Like BNP, Di dimer etc)
  • Finally it is  a  cheap investigation and hence  lacks the required glamor.

Technical limitations

  • Uric acid levels are non specific (Like any other  modern  molecules  Tropinin , CRP etc! ) No one  would like  to compare uric acid vs hs CRP one to one as a marker of inflammation in vascular  disease.
  • UA  levels depend on kidney function .
  • Dietary influence can be significant (Especially meat, Liver Beans, Cauliflower etc)

Knowing the  basal level of uric acid  in a given patient ,   help us  monitor the net cell turnover during medical   management of chronic illness.

UA’s Clinical utility in cardiology practice

Importance of UA in PAH   is well recognised now  . Most studies on PAH  use it as a marker  or even  to define a therapeutic endpoint  But , please remember  elevated uric acid is a  simple  index of elevated  cell turnover and oxidative stress and it mainly represent  the effect of  pathology rather than a pathology itself.

So , attempting to reduce uric acid levels   with drugs like  Allopurinol may not  improve the  vascular function as one would wish ! The only indication for  reducing uric acid level   is  when the levels   become  too much and it starts depositing   in body.

Final message

Uric acid is a useful bio marker for  vascular function. It can indicate  the  quantum of  inflammatory , metabolic  and cell turnover of any progressive vascular  disease. With serial measurements  it definitely helps us in monitoring   cardiovascular disease  especially pulmonary hypertension  as  lung tissue is major source of this molecule . Now , uric acid  is used  for prognosticating  cardiac failure also.

Reference

http://qjmed.oxfordjournals.org/content/93/11/707.full.pdf+html

 

 

 

 

http://ajrccm.atsjournals.org/cgi/reprint/160/2/487?ijkey=dc24281a22fcf54ed27ac4466393abd691047408

http://cel.webofknowledge.com

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