Urate level in blood and cardiovascular disease
I went back over the literature again to confirm that there is noevidence I could find to suggest that allopurinol has any affect onuric acid that has already formed in your body. The mechanism ofaction of allopurinol is to stop the formation of new uric acid.While reading various references, I ran across several very recentreferences that are very important to us.
Earlier medical literature has noted the relationship between goutsufferers and hypertension-(high blood pressure) as well as asimilar correlation with corronary heart disease. Until veryrecently this was thought to be a co-effect of gout, perhaps, it hasbeen suggested, that gout and hypertension are caused by the same, orat least similar, metabolic conditions.
I would suggest that you read at least the first reference I willgive because it is a startling result.
1) http://www.rheumatology.hss.edu/phys/specialReports/uricAcid.asp(July 1, 2003) Theodore R. Fields, MD, FACPInternet Project Director, HSS Division of RheumatologyDirector, HSS Rheumatology Faculty Practice PlanAssociate Professor of Clinical Medicine, Weill Medical College ofCornell UniversityUric Acid and Cardiovascular Disease - Chicken or the Egg? New AnimalData Suggest Possible Pathogenic Role of Urate.
2) Hypertension. 2003 Jun;41(6):1183-90. Johnson RJ, Kang DH, Feig D,Kivlighn S, Kanellis J, Watanabe S, Tuttle KR, Rodriguez-Iturbe B,Herrera-Acosta J, Mazzali M:Is there a pathogenetic role for uric Acid in hypertension andcardiovascular and renal disease?
3) Hypertension. 2000 Dec;36(6):1072-8. Verdecchia P, Schillaci G,Reboldi G, Santeusanio F, Porcellati C, Brunetti P.Relation between serum uric acid and risk of cardiovascular diseasein essential hypertension. The PIUMA study.
4) Hypertension. 2001 Nov;38(5):1101-6. Mazzali M, Hughes J, Kim YG,Jefferson JA, Kang DH, Gordon KL, Lan HY, Kivlighn S, Johnson RJ.Elevated uric acid increases blood pressure in the rat by a novelcrystal-independent mechanism.
In order to keep from upsetting anyone as to why I say these things,I will quote from the first reference cited here.
Dr. Fields writes:
“Recent animal studies, however, suggest an independent risk statusof urate.3 Rat data in this study suggested that urate appears to bepathogenic of hypertension, arteriolar wall thickening, andendothelial dysfunction. Mild induced hyperuricemia (using a uricaseinhibitor which does not lead to crystal deposition in the kidney andpreserves renal function) causes hypertension in the rat withinseveral weeks, with stimulation of the renin-angiotensin system andinhibition of NO synthase (and renal injury and fibrosis).
In this model, blood pressure changes were prevented if allopurinolwas given early. Chronically hyperuricemic rats showed salt-sensitivity and thickening of the afferent artery of the glomerulusand tubulointerstitial inflammation and fibrosis - which did notreverse if allopurinol was given late. Hyperuricemia stimulated ratvascular smooth muscle cell proliferation and induced endothelialdysfunction.”
That may be hard to absorb but the bottom line is that when theyartifically induce high urate levels in rats, those rats develop highblood pressure and they develop hardening and thickening of thearteries. More importantly, when those rate were fed allopurinolearly in the test, the hypertension symptoms did not appear. If thesymptoms were allowed to go too long, they were not reversible.
The excess uric acid that we are accumulating from our gout conditionis much more dangerous than just the pain we feel from the attacks.
The high levels of urate in our blood is causing severe andeventually non-reversible cardio-vascular problems.
Based on this finding I plan to get my physician to increase mydosage of allopurinol to a level known to stop urate productionaltogether and then titrate my system back to the optimum level. Thatis, I will move the dosage level down, slowly, based on any badreaction to the drug, based on serum urate levels in the blood andbased on how my gout attacks are progressing.
Some of you have stated your reservations about taking allopurinol,as I did, but allopurinol is indicated for gout sufferers and to myway of looking at it, this is cardio-vascular implication is the mostpersuasive of all the information I have read. I can live a long timewith a pain in my foot, I cannot live very long if my heart and myarterial system are compromized.
Charlsie Santanna on May 1st, 2007
what is your current dosagesince i may want to try a similar one, or at least be familiar withthe dosage possibilities. what about gout attacks caused by toosudden an influx of allopurinol.??
Sabina Shamel on May 3rd, 2007
“what is your current dosage?”100 mg, once a dayProbably be aised after 3 months but need to test urate level first.
“what about gout attacks caused by too sudden an influx ofallopurinol”
I have heard that, and my physician warned me to expect it and,indeed, I have been getting small atatcks. In fact the plan was towait till my most recent attack subsided but since it didn’t looklike it was going to subside soon, I just went on allopurinol anyway.
I don’t know why there should be an increase in gout attacks becauseof starting allopurinol. I cannot figure out a mechanism. Doesn’tmean there isn’t one but I just can’t figure it out. Moreover, I’mnot sure whether it had any effect at all on my current wave ofattacks which, by the way, seem to be gone now that I am off coffee.
In any event, it’s worth the risk, if you have had two gout attacks,take allopurinol. If you have had only one you might not get anotherso you should wait. But, if you have had that second, there is a 99%chance you will get a third, fourth and on and on.
Terrance Molock on May 3rd, 2007
“Gout attacks caused by too sudden an influx of allopurinol”. I do not believe there is an answer to this question.I think itis far too complicated..and with far too many variables. I am going to try and offer you some explanations..from experts. I’m not in any way being critical of you..of course not..but Iwant to take a look at your statement..”too sudden..an influx ofallopurinol” There is really no way of determining what is too sudden.
We have to go back to square one for a bit.We have a patient whowants no more gout attacks.So he decides..that the best way for thisis to accept the fact that there is really not anything that he cando about it..and he is willing to go on drugs every single day forthe rest of his life.This is a VERY tough hurdle.There is researchnow that says that the most common cause of gout attacks..(this isbased on people seeking treatment at clinics,hospital emergency wards)((This incidentally is not uncommon..people trying to go off it..Iknow plenty of people that have tried this))is going offallopurinol.Going off..pretty much guarantees the attacks will bemore severe.The body gets used to..and addicted to allopurinol. Historically..allopurinol is the only thing that really works.Wehave to agree first on some basics:..let’s forget about triggers forthe attacks,white blood cell attacks,even dealing with theattacks.Let’s even forget for a second about blood uric acidlevels.What we have are crystals in our joints/fluid/areas.Let’s notget ahead of ourselves and think about the fact that the white bloodcells..may..attacks them..may..when the chemcial condtions are right. These crystals have to go.First and foremost.Once the crystalsare gone..problem over. The crystals get there because somehow..unknown..enough uric acidmanages to get into the joint fluid..and when it’s percentage is highenough..crystals. If we accept this and move backwards and say..ok..then how do weprevent this uric acid in those amounts from getting into the jointfluid.There is research going on on drugs that do not specificallydeal with the uric acid in the blood.We do know..just from the sheerpercentage of people that have high uric acid in their blood..andnever get gout.The fact is that almost all Dr.s,research says toleave the high uric acid levels alone..unless there is gout/stones. These drugs that will deal only with the uric acid in the jointfluid..crystals are not here yet. The only drug that may be even close to this ideal iscolchicine..howevere..colchicine does not deal with the crystals..oruric acid/levels..it’s mechanisms are still debated/not fullyunderstood.Why colchicine pretty much only affects the white bloodcell attack on gout crystals..is still not clearly understood.
So we have this uric acid in the blood that is getting into thejoint fluid in too great amounts and causing crystals.To get rid ofthe crystals..we need about a 20-30% reduction in blood uric acidlevels..note:..not to some/any arbitrary level..but to a level thatreduces the amount going into the synovial fluid.The only way to dothis.at this point in history..is allopurinol.(Well..of course thereare the drugs like probenicid that instead of targeting theproduction of uric acid they increase the disposal of it..this drugis not nearly as popular and has more side effects..but is still used) We get said patient..and hopefully after his first attack/ormedical history..we have a baseline to deal with.If not we need arough baseline.What we really need is a series of average uric acidlevels..1 every few months..and no major changes indiet/exercise..and no gout attacks either.After the nextattack/attacks..we can look at these levels and say..ok this patienthas crystals in his joint fluid at an average blood uric acid levelof x..we know that by reducing this average level of about 20-30 %that the crystals will leave. It is not so simple..said patient has had numerous,numerousattacks over the years..maybe..probablly a middle aged male..hasn’tseen a doctor in years..no history of uric acid levels.But now in themiddle of an attack that he can no longerhandle/manage/control..maybe it won’t stop/has caused permanentdamage..but he right now..wants no more of them.Fair enough.Gimmeethe allopurinol.The Dr.yanks a blood sample..it maybelow..often..hmmm..maybe this guy doesn’t have gout..a savvyDr..says..ok sneaky gout..I know that during an attack the level canbe lower because the crystals have precipitated out..but where isthis guy in determining a “normal” working uric acid level? So the allopurinol is started..usually they start at an averageof 300mg day and check blood uric acid levels adjusting asneccessary.If the level is dropping too fast..lower..not droppingfast enough..higher.Some Dr.s start at 100 and work up..some at 900and work down. This is where the attacks can occur.Seeing as how it isimpossible to predict an attack(at a certain stage) it is alsoimpossible to know exactly when/how to dose the allopurinol.Let’s saythat the patient is VERY close to an attack..who knows? the patient?no..the Dr.? No..so that he is between attacks and the allopurinol isstarted..unbeknownst..JUST before an attack wqas tostart..whammo..attack.. We know that attacks can be caused by rising or lowerring uricacid levels..allopurinol is pretty powerful at lowerring them.Saidperson takes the allopurinol..and the body chemistry says..”what isthis?”..this ain’t no purine that can have a very small effect..thisis something that tells the body..ok don’t make so much uricacid..and can have a major impact.Ok..so quickly the source of 95-97%of the bodies uric acid is reined in..it’s productioncontrolled..reduced. Initially sure there is a plunge in uric acid level..blood drawnat the arm.A body average.This is not the blood uric acid level atthe joint area..this can be far higher. We now have the overall uric acid level plunging..and this isgood..and bad.The body still wants to maintain and regulate what itthinks is correct..depending on how long the person has had goutfor..and other factors..determines the bodies storehouse of existinguric acid(deposits)..and where it is.There are chemical resaons forit building up in some areas..as well as blood flow.IT buildsup,concentrates and gets ready to crystalize.There obviouslly is ahigher concentration of uric acid.And it is gradually buildingup..with new uric acid arriving all the time..adding to themixture.Along comes Mr Allopurinol and says..”sorry..we’re cuttingback on the uric acid delivery..here how about allowing some otherbody fluids to circulate here..obviouslly the uricacid/crystals/deposits in that area are now going to be put in a muchweaker solution..one low enough that it can’t crystalize. Some of these crystals,deposits,just dissolve,end up back in thejoint fluid,eventually getting flushed out and back in the bloodstream,getting filtered,passed in urine. Other crystals do not “Go gently into that good night”..they getdisturbed..uprooted..crystals that lay harmlessly entangled in uricacid deposits..or floating around..some loose crystals get the sametreatment..”seeing as how the other crystals are dissolving andheading back into the bloodstream you can too”..well..with the nowincreased flow..they get stuck..white blood cells attack.Minutechanges in the actual uric acid level in the joint fluid have beenknow to strip the protein coating from the crystals..this causes achemcial to be released that the white blood cells recognize ashostile.This stripping of the protein coating of urc acid crystals isbelieved to be the first sign of their demise.However this strippingcan also be caused by an increase in joint uric acid levels. Some deposits that lay dormant are now out back into thebloodstream..thus now temporarily raisng the overall blood uric acidlevel..these deposits can move to other areas before they getfiltered out.This can be a vicious cycle..for a while.I know that mygout attacks moved from hips to toes to feet..then with theallopurinol they moved to my shoulders,elbows and thumbs before Iguess..HOPE left.
On going on allopurinol..more Dr’s are now starting patients onvery low dosages of colchicne..to get them used to it.Colchicinen canand does upset the stomach..in traditonal doses..but apparentlly thebody can adjust to it.When a “maintenance” dose of colchicine isestablished..on or around that time..allopurinol isstarted.Colchicine is very,very effective..much,much more effectiveat preventing gout attacks than dealing with them.Colchiccine at thevery beginning of an attack..delivers a hammer blow to a goutattack..but introduced during an attack..is not nearly effective..butit can and is prescribed with other drugs. There are “goutees” such as me that never have any discrepanciesin uric acid levels..just the sudden intial drop as the allopurinollowers the uric acid level in the blood(measured at the arm) andothers who such wide swings that the Dr’s see a too close monitoringor uric acid levels as meaningless..so they just use maybe 4/5 monthtest intervals. The rheumatologist I see starts thecolchicine,indomethicine,allopurinol..for a year or two..with VERYclosely monitored blood tests!This he has found is the best way todeal with gout..past deposits,current uric acid problems,currentattacks, and preventing future attacks.
Hope this helps..whew this gout is confusing..