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A substantial body of epidemiological and experimental evidence suggests that serum uric acid is an important, independent risk factor for cardiovascular and renal disease especially in patients with hypertension, heart failure, or diabetes. Elevated serum uric acid is highly predictive of mortality in patients with heart failure or coronary artery disease and of cardiovascular events in patients with diabetes. Further, patients with hypertension and hyperuricemia have a 3- to 5-fold increased risk of experiencing coronary artery disease or cerebrovascular disease compared with patients with normal uric acid levels.
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That is the Intro to the SUMMARY of a lengthy report in Medscape about the SECOND most important consequence of high uric acid.
Please read the article: it may be of MORTAL consequence.
http://www.medscape.com/viewarticle/472684
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If you need to register with Medscape to get it, then let me know and perhaps I can cut and paste the whole thing, or consider registering with Medscape, it's free.
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If this was reported before somewhere else on Gout Pal, then it bears repeating. 😀
For access to the report, it looks like you can read it page by page following zip2play's link, but if you want to see the whole thing on one page at http://www.medscape.com/viewarticle/472684_print you have to login. As zip2play says, registration is free, or at least as free as GoutPal is (i.e. don't get fooled into seeing adverts as facts).
Most interesting, to me, from that 2004 review, is the conclusion towards the end of the report:
Elevated serum uric acid in hypertensive patients has been associated with a 3- to 5-fold increased risk of coronary artery disease or cerebrovascular disease compared with patients with normal uric acid levels. Collectively, these studies suggest that serum uric acid may be a powerful tool to help identify patients at high risk of CVD. Serum uric acid should therefore be considered along with other risk factors, such as obesity, hyperlipidemia, and hyperglycemia, in the assessment of overall CV risk.
The remaining key questions are whether uric acid has a causal relation to CV disease, whether a reduction would prevent CV and renal disease, and whether uric acid can be reduced to an optimal level whereby it no longer imposes an increased risk for CV disease. The LIFE study findings are encouraging. However, these issues can only be settled definitively through randomized clinical trials. Until then, the belief that treatment to reduce hyperuricemia will be cardioprotective must rest on observational and mechanistic evidence.
Since it was published, PubMed lists over 1000 results for “uric acid cardiovascular.” I didn't spot a randomized clinical trial, but I did see some interesting statistics relating to allopurinol and mortality (the 2002 study is referenced in the Medsape review.
2002: Effect of allopurinol on mortality and hospitalisations in chronic heart failure: a retrospective cohort study.
Long term high dose?allopurinol?may be associated with a better?mortality?than long term low dose?allopurinol?in patients with CHF [Chronic Heart Failure] because of a dose related beneficial effect of?allopurinol?against the well described adverse effect of urate. Further work is required to substantiate or refute this finding.
2009:Allopurinol and mortality in hyperuricaemic patients.
Our findings indicate that?allopurinol?treatment may provide a survival benefit among patients with hyperuricaemia.
2009: Association between allopurinol and mortality in heart failure patients: a long-term follow-up study.
The prevalent high-dose?allopurinol?use had a lower risk of?mortality?than the prevalent low-dose use suggesting that?allopurinol?may be of benefit in HF [Heart Failure] patients.
Only one of these [2002] mentions the definition of high/low dose, with high being 300mg or more.
The Medscape review also mentions potential benefits of losartan and atenolol (common treatments for high blood pressure), but I haven't looked into those.
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As an allopurinol user, my personal view is, if you accept that allopurinol will help your gout, ffs (that means please), make sure your dose is high enough (after the initial 100mg safety test), and never settle for uric acid levels greater than 5mg/dL (0.30mmol/L).
Zip2play, your article also prompted me to see how allopurimol is becoming significant for heart disease and other diexeases. Did you see http://www.goutpal.com/2927/have-a-heart-allopurinol-helps-more-than-gout/
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I am voracious in reading anything that will increase my useful lifespan. I have confirmed coronary artery disease that I am trying hard to hold in check or even reverse. I have excellent control over my LDL levels, modest control over my Lp(a) levels and tolerablle control over my urate levels. On the last item, I feel I can do better.
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Let's get personal GP:
I know you are/were taking 900 mg. allopurinol/day to get rid of old tophi as quickly as possible. How is that working out? ?What kind of SUA's are you running on this dose? Are you seeing diminution of your elbow tophi (if I rememberr correctly.)
I will see ANOTHER new doctor soon (Goddamned private insurance nonsense in the USA) and am torn between an increase in allopurinol (to 400-600mg) or the addition of probenecid, perhaps 500mg to my 300 mg alloprinol. I am only getting in the upper 5's and lower 6's with the 300 mg. allopurinol and, although keeping frank gout attacks away permanently, I am having a deuce of a time with joint pains and a wonky right hand with a painful trigger finger.
I know from?a few posters here that alloputrinol shows a rather steep marginal diminshment of benefit with increasing dosage. I presume you've seen the same.
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And of course, I would like to take full advantage of any cardiac benefits from allopurinol and/or very low urate levels.
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So, how is the 900 mg. dose working out for you. (Just between us turkey talkers.
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Do you have any thoughts on increased allopurinol vs. addition of probenecid? Any cautions on very high dose allopurinol, since you are a sample of one, our canary in the coal mine.
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Of course anyone else who wishes to voice an opinion is very welcome.
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(I pray this next doctor will inderstand that I know what I am talking about when I ask for something…otherwise there will quickly be yet ANOTHER doctor, and ANOTHER.
?I should NOT have to argue with my “employees.”)
The high doses of allopurinol in the reports I have read, about uric acid and heart disease, are 300mg or more. With 100mg or less classed as low.
Though my father was sadly a victim to heart disease, I personally do not have any history, and all relevant tests have been good, except that my weight and cholesterol are on the high side.
Since achieving my urate lowering targets with allopurinol, I have been more concerned about the cholesterol than about the gout. I am trying to lose weight, and failing miserably. I am also putting off revisiting my doctor until I have lost some weight. It does not help that all doctors seem to be obsessed by irrelevant numbers these days. I had a battle to overcome the ridiculous notion that statistical averages of uric acid levels in a general population should dictate medical treatment for lowering uric acid levels. It has left me with a suspicion that these people really do not think about what they are doing, so if the numbers say prescribe a pill, then it gets forced on you. If the numbers do not qualify you for treatment, then no amount of pain and discomfort is going to persuade them otherwise. Sorry about that rant – I'm just trying to justify not going to the doctors. No excuse really, so I'll use the prompt of your message to book an appointment – ma?ana.
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So back to my allopurinol experience, which is interesting despite having no relevance to heart disease.
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New readers should be aware that I battled long and hard with various doctors. Armed with professional rheumatologists recommendations that 5mg/dL (0.30mmol/L) is the best, safest target. and armed with reports that lower levels reduce tophi faster, and armed with several visble tophi, I bravely fought the beast of doctorly ignorance, and pushed allopurinol dosing to it's limits to get my uric acid as low as possible. I hit 900mg maximum dose some time last September/October.
Somewhere around here is a chart of my progress, which I will get round to updating when current weariness from man flu subsides.
Anyway, you must be bored with this rambling, so I'll get to the point, and answer your specifics:
1. Uric acid is running around 4.
2. Tophi are shrinking as follows:
Pea sized lump on left knee has disappeared
Grape-pip profusion on left elbow has fewer pips (looking forward to the seedless variety)
Half-a-thumb sized lump on right elbow is now half a pinky. This has a very solid feel in places, so I just prod and squeeze it to try and encourage faster shrinking. I have no idea if this is helping, but it does reinforce my view that it is shrinking.
3. My only thoughts on probenecid to support allopurinol are:
It sounds like a good idea – combination therapies are often much more effective that a single treatment, especially when they target different aspects of the same problem.
Personally, I would only consider it if I was failing to achieve target uric acid level.
It makes sense to take 24 hour urine test before initiating probenecid, then again after one month. Alhtough baseline will be reduced by allopurinol, this will determine if extra uric acid excretion is being achieved. This is my view based on logic, and I have not seen any professional evaluation of such a plan.
4. I have absolutely no cautions about full dose allopurinol, just as I have no cautions about full dose of ibuprofen or full dose of colchine or full dose of any other medication. In fact, I cannot see why anyone would want less than the full dose, until they were confident that all uric acid deposits had dissolved. I have a specific warning about kidney and liver function tests when you take any uric acid lowering treatment. I have been lax about this, but tests three months ago were fine on 900mg, which is probably why I didn't have to fight too much to maintain that dose.
5. I know you didn't ask specifically, but everyone wants to know about gout flares. I seem to remember commenting a few months ago that I was pleased to see that I could manage any gout flare with a combination of a couple of colchicne and some max-strength ibuprofen. Possibly helped by a warm blanket and the tender loving care of my beautiful wife (just in case she sees this – I need help with the man flu). I now get a minor flare about once every two or three weeks, which I put down to some re-awakening of stubborn crystals hidden deep within the joints and tissues. I usually leave these to pass in a day or so as I wallow in the fond memory of former tortures. The colchicine fell behind my bedside table when I last felt the need before Xmas – and there it stays.
Thanks GP.
Happy to hear your tophi are shrinking.
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Reading between the lines with my SHerlock Holmes magnifying glass ?I can tell you are on the horns of a dilemma about STATINS. I think they are God;s gift to man right below allopurinol in their glory.
But, since they are not without side effects, I cannot gainsay anyone's wariness about them.
BUT, take an aspirin every day. THIS I DEMAND! :D?There is no lottery win?quite like skipping a heart attack that you might have otherwise?had.
zip2play said:
BUT, take an aspirin every day. THIS I DEMAND! :D?There is no lottery win?quite like skipping a heart attack that you might have otherwise?had.
If only things were that simple
Take that srticle with a grain of salt. Meta-anaysis usually sucks. Drawing consclusions OTHER the one being investigated sucks (article purported to be studying the relationship to cancer and aspirin.)
Slanting studies with nomenclature like seeing “non-trivial bleed” in the data but maginifying it to MAJOR bleed in the conclusion shows extreme bias. Ignored in comparing PERCENTAGES is the actual number: to wit, more than half of us will die of a heart attack, a HUGE number of people. VERY few will die of “non-trivial bleeds” so a 30% decrease in the former is is a gargantuan health benefit but a 30% inclease in the latter is almost inconsequential.
Like saying don't take a lifesaving drug that will save MILLIONS becasue of a 10% increase?in the death rate from an infected toenail.
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Since the advent of the VERY VERY expensive blood thinner, Plavix and her even more expensive patened sisters, aspirin get pooh-poohed by studies, especially META studies that need only buy one “researcher,”?financed by some “unknown donor.” <tongue planted firmly in cheek>
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I's reminiscent of all the bad press that allopurinol got COINCIDENTALLY at the same time Uloric was being rolled out.
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The cardioprotective effects of aspirin is the most important medical discovery of the Twentieth Centruy. If it could be patented it would be touted as a MIRACLE and cost $100 a pill.
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Perhaps 10 year olds don't need it daily but post-50 year old men certainly DO. Post 50 year old men with gout probably stand 75+%? chance of death by heart disease.
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My triumvirate of the wonders of Twentieth Century medicine are: penicillin, Lipitor, allopurinol, and aspirin (ancient drug but with new?20th Century capability.)
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And don't be surprised if you read more about decreased gastrointestinal cancers among aspirin users?but that will only be icing on the cake. Heck, if aspirin can tear a tiny, undetectable?cancer off of my colon, who cares if the site bleeds a little.
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I am having a problem of my own regarding aspirin. I have many joint pains, back, shoulder, hand, sore feet. AND I am a sexagenarian weight lifter?PAIN! Maybe some gout, maybe some osteoarthritis, maybe some being too old for the gym.
In any case I would like to take naproxyn daily but all NSAIDS tend to interfere with the permanent platelet anti-agglomerating effect of aspirin. I am having trouble finding what I would consider the last word on the subject. Obviously all NSAID manufacturers will show studies that paint there own drugs in a favorable light so I am having “trust issues.”
Having proven cardiac vessel partial blockages, the issue of clot prevention is paramount in my mind.
Because people who have high Uric Acid have a bad lifestyle that causes the High Uric Acid in the first place?
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That seems not to be true. Improper uric acid disposal is a genetic evolutionalry “defect.” Perhaps not even a defect. I once saw a farily believable correllation between gout and high intelligence. I know that those with high musculature, certainly not a defect, have a high correllation with gout presumably because of release of nucleic acids?(RNA and DNA)?which break down to xanthines and then to?uric acid. (Yep?Surprise, another benefit? of allopurinol on NION dietary xanthines.
Uric acid convey some sort of advantage to humans but WHAT that advantage is is elusive and unfortunately it conveys detrimental qualities, like gout and heart disease. My best guess, and a guess it is, is that uric acid, especially when crystallized is considered foreign by the immune system and it begins an assault. On a macro level we see it as a massive purple toe warmed by the fires of Hell. But consider the same process on a micro level at the surface of a coronary artery. That same inflammatory process and the same kind of scarring might account for the initiation of a fatty plaque.
?I am convinced that man lost the ability to break down urates, almost UNIQUE in the animal world, for an evolutionary advantage. That's the way evolution works. This advantage? is just not easy to understand. But often an evolutionary advantage is a two sided coin. We can walk on two legs and use our arms to battle an enemy?but that advantage also convers the curse of the “bad back” which is the plague of MANY!.
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It is sad though that one of the DISadvantages has to be coronary artery disease?a real BIGGIE. Too bad evolution is not much use here?because we men who are most likely to get the disease have already done our spawning by the time gout rears its ugly head. There is not much evolutionary advantage gained by keeping 50 and 60 year old men alive.
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Another “partially baked” train of thought is that species evolution is SLOW but human “civilization” moves quickly. Gout is a disease of meat eaters and for most of man's history he has been a plant eater?except for the kings and priests who could afford meat and got animal “sacrifices for the “Gods.”?These privileged few got GOUT.??In animal speciies, I posit that the carnivores quickly developed the enzymes? to break down urate. Man hasn't been eating meat long enough to develop this evolutionary trait and the “meat at every meal” is a very new concept for the common man, and only in the wealthier societies, perhaps less than a century old.
Remember the promise of the DREAM, “a chicken in every pot”?on SUNDAY!
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Maybe in a few more millennia we willl produce uricase.
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So while I agree that an improper high fat, high calorie diet and slothful (and SLOSHFUL)?ways may generate heart disease, I doubt it has much to do with gout or uric acid buildup.
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