Warfarin and systemic calcification?

[tigerlily]

I was wondering if any of you know anything about the following quote and whether there is a way to prevent warfarin from increasing systemic calcification. It sounds like over time, it could be a big problem but I'm hoping that's not true. I've been thinking a lot about if and when I need to have my tissue valve replaced, whether to go with another tissue or a mechanical valve. I know that sometimes there isn't a choice and you do what you have to do regardless. The quote is from The American Journal of Medicine blog and I couldn't read the whole article since I'm not a member. Here is the url - http://amjmed.org/warfarin-and-vascular-calcification/

"Use of warfarin is associated with an increase in systemic calcification, including in the coronary and peripheral vasculature. This increase in vascular calcification is due to inhibition of the enzyme matrix gamma-carboxyglutamate Gla protein (MGP). MGP is a vitamin K-dependent protein that ordinarily prevents systemic calcification by scavenging calcium phosphate in the tissues."

 

[pellicle]

that's funny ...

there is just as many people saying its associated with removal of calcium ... which is it ?? Perhaps neither

My vote is that its neither.

Much is written on stuff that is weakly linked ... it gives researchers a budget.

The blog you linked to bases its views on the following single reference to the subject

http://www.ncbi.nlm.nih.gov/pubmed/21775389

METHODS AND RESULTS:

A prospective coronary calcium scan was performed in 157 AF patients without significant cardiovascular disease (108 males; mean age 57 ± 9 years). A total of 71 (45%) patients were chronic VKA users. The duration of VKA treatment varied between 6 and 143 months (mean 46 months). No significant differences in clinical characteristics were found between patients on VKA treatment and non-anticoagulated patients. However, median coronary artery calcium scores differed significantly between patients without and patients with VKA treatment [0, inter-quartile range (IQR) 0-40, vs. 29, IQR 0-184; P = 0.001]. Mean coronary calcium scores increased with the duration of VKA use (no VKA: 53 ± 115, 6-60 months on VKA: 90 ± 167, and >60 months on VKA: 236 ± 278; P < 0.001). Multivariable logistic regression analysis revealed that age and VKA treatment were significantly related to increased coronary calcium score.

So, of the 157 patients (of which we know bugger all about) only 45% were long term warfarin users (chronic VKA) ... hardly conclusive if you ask me. I notice that they determine AGE and VKA are significant factors.

But hey, lets ignore age and go for the enemy warfarin ...

For balance I suggest you read this link to a 2010 study:

http://onlinelibrary.wiley.com/doi/1.../clc.20865/pdf

In a cross-sectional analysis of 70 patients (46 men, mean age 68 ± 13 years) on warfarin therapy without known coronary artery disease, after adjustment for cardiovascular risk factors, no correlation between warfarin duration and coronary artery calcification ...
...
These preliminary studies do suggest an association of warfarin use with calcification, but the potential relationship warrants larger prospective randomized studies to better evaluate this relationship. Based on the available data, we do not currently recommend screening for vascular calcification before initiation of warfarin therapy. It is still unclear whether warfarin-associated calcification isclinically significant enough to affect the morbidity and mortality associated with vascular and valvular calcification

so basically they are of the view that its so insignificant its not even worth screening patients.

IMO crossing the road is more dangerous

Of note they seems to mention dabigatran a lot as a potential alternative (which it isn't) and since that costs a LOT more I'd wonder if there is a "skeleton in the closet" hunt to scare up business for the alternatives (like dabigatran which makes more profit).

In their abstract they say:

Newer anticoagulants such as dabigatran and rivaroxaban offer promise as future therapeutic options in such cases

but in their summary they also say (I'll bold what jumped out at me):

Warfarin still remains the least expensive and most widely available mode of anticoagulation with long-term expertise in managing it, and inexpensive testing for monitoring the dose. It has a proven benefit in preventing strokes in AF patients, recurrent deep venous thrombosis and pulmonary embolism, and in reducing mortality in patient populations at risk for thromboembolic disease. Warfarin is also fairly quickly reversible in case of bleeding and can be safely used in patients with low creatinine clearance. However, the use of warfarin has always been difficult because of complex pharmacodynamics, a narrow therapeutic window, numerous drug-drug and drug-food interactions, and multiple adverse effects.

I love the "difficult" ... because of dipstick clinics just wanting a quick money grab for a simple task of monitoring which they usually cock-up


Then in this study that finds a link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2517807/
In their methods they admit to overdosing the rats

[FONT=&quot] Ten rats were treated daily with a subcutaneous injection of sodium warfarin (100 mg/kg) [/FONT]

so, as I weigh 75Kg if they were dosing me they'd have give me 7000mg of warfarin ... naturally I'd die.

so would the rats ... if they hadn't also done:

[FONT=&quot]and 10 mg/kg vitamin K1[/FONT]

so they gave them what would have been a lethal dose if not for the administration of an antidote to prevent them dying ...

they then observe:

Rationale for the animal model

[FONT=&quot]The animal model used in this study is not completely analogous to the human receiving warfarin. Ideally we would have treated the rats with warfarin on its own to cause an increased clotting time as occurs in the human. However, it is difficult to maintain rats on a therapeutic dose of warfarin due to coprophagia which results in unpredictable dosing. [/FONT]

got to love coprophagia (and I'm not clear if its the rats or the research model that's eating ****)

meaning "we gave them too much, but we couldn't be bothered in administering such small amounts. OR perhaps "we didn't see any effect till we gave them 10 times a lethal dose + an antidote to the poision"

Also, you'll note us valvers are ignored ... meaning they're after a bigger market ... I'll stay with warfarin thanks.

 

[Agian]

The other option is to take Vitamin K and adjust your Warfarin dose accordingly. Why not?

 

[pellicle]

The other option is to take Vitamin K and adjust your Warfarin dose accordingly. Why not?

Gym guy does just that

 

[Agian]

Do you know what specifically? Apparently there's a couple of formulations out there.

 

[Agian]

Wait a second. Did you say rats eat their own ****?

 

[pellicle]

Wait a second. Did you say rats eat their own ****?

its in that journal article

anyway ... for sure it happens ... I've seen enough evidence emerge from Canberra that rats are coprophages ... particularly that sub-species.

 

[Nocturne]

I'm very concerned about this issue, given my advanced coronary artery calcification for a man my age. My hope is that I'll be able to hang in the waiting room for 10-20 years, and that by then there will be a more viable bioprosthetic or mechanical valve option that does not require warfarin. It could happen.

But if I were to need surgery tomorrow, I have to say I'd be leaning strongly towards a bioprosthetic. I've read several studies revealing that lifespan after surgery is about the same for either type of valve, and that risk of stroke is greater with a mechanical valve. Meanwhile my wife, who is a hematologist, is of the opinion that warfarin is a great drug to avoid having to take if possible. And of course there's this issue with calcification.

One of the studies you mention had less than 100 participants. That's an almost meaningless study. Too much chance for an odd group of people to skew the data. The conclusion of that study was that they didn't know one way or the other, and recommended further study, and to proceed with caution (i.e. Conservatively, i.e. Follow established guidelines) until more research is done. Which is pretty sensible advice for practitioners, but as an individual, you don't want to be the guy who learns ten years after the fact that yeah, warfarin has been giving you a push forward in the pine box derby all this time, and will for the rest of your life, too bad so sad. Certainly not when you weren't likely to enjoy any fewer years if you'd gone with the bioprosthetic and future studies had confirmed that warfarin DIDN'T accelerate the progression of CAC (coronary artery calcification). And in my case, I'm one of the people for whom a finding that "well yeah, it DOES accelerate CAC progression, but not by enough that it will matter to the average Joe" is NOT going to be enough, because I'm already far on the wrong side of the CAC bell curve.

That's just my reasoning, for myself.

Oh, and also, if I were really to need the surgery tomorrow, I'd be 42, and likely young enough if/when a bioprosthetic replacement was needed that survival through a second surgery -- after 10-20 years of medical advances -- would not be much of a problem.

But honestly, my hope is that by the time I need the valve replaced, we'll see a significant advance in bioprosthetic valve tech, mechanical valve tech, and/or medicine and I won't have to make the big "repeat surgery or rat poison" decision.

 

[pellicle]

...Which is pretty sensible advice for practitioners, but as an individual, you don't want to be the guy who learns ten years after the fact that yeah, warfarin has been giving you a push forward in the pine box derby all this time, and will for the rest of your life.

except as I mentioned there is no evidence to support the idea ... there is a heap of people such as dick who have been on it for decades longer than anyone in that survery with no effect

 

[Agian]

Calcification is a product of arterial plaque. Look it up. it starts off as fatty streaks and builds up from there. Calcium just doesn't miraculously appear in one's arteries just because someone is on Warfarin. Address CAD and there's nothing to calcify. Does Warfarin contribute to CAD? You'd know about it long before it even got to the calcification phase, if it did. To go from fatty streaking to calcification takes many years. Get your lipids under control. Calcified plaques cause angina, but not heart attacks. Heart attacks are caused by fragile soft plaques that break up and cause clots. Warfarin minimises clots, btw.

 

[Agian]

PS, you'll probably get your wish anyway.

Triflomedical.com

 

[Agian]

its in that journal article

anyway ... for sure it happens ... I've seen enough evidence emerge from Canberra that rats are coprophages ... particularly that sub-species.

Sub species of bottom-feeding sycophants that bludge off the tax-payer's money and make a career talking **** and polishing poles.... You're being unfair to rats, now.

 

[cldlhd]

The other option is to take Vitamin K and adjust your Warfarin dose accordingly. Why not?

If you did that, took vitamin k2 and upper the warfarin dose, would it just offset?

 

[cldlhd]

Calcification is a product of arterial plaque. Look it up. it starts off as fatty streaks and builds up from there. Calcium just doesn't miraculously appear in one's arteries just because someone is on Warfarin. Address CAD and there's nothing to calcify. Does Warfarin contribute to CAD? You'd know about it long before it even got to the calcification phase, if it did. To go from fatty streaking to calcification takes many years. Get your lipids under control. Calcified plaques cause angina, but not heart attacks. Heart attacks are caused by fragile soft plaques that break up and cause clots. Warfarin minimises clots, btw.

I don't think that's definitive either. There are other theories that calcification in arteries can result from arterial damage from things like high blood pressure or inflammation. The reality is none of us out here know for sure. One study is 157 men the other is 70 so neither are very large so it might be a bit of pick the one you like if it reinforces what you already believe. I think examples like Dick are great but as evidence anecdotal. It tells me that while k2, or lack thereof, MAY effect calcification there are surely other factors such as genetics and overall health. I admit I haven't dug into this subject as much as others because I'm not on warfarin but I know I could be one day and obviously calcification is a concern for a lot of people out here. I suspect there is a probable connection between warfarin and increased calcification especially if you already have a propensity for it but even so at the age of 45 when I had my surgery last year I told the surgeon I wanted mechanical if my valve wasn't repairable.

 

[Agian]

I'm guessing you'd probably have to increase your dose of Warfarin, but so what?
Pel reckons "gym guy" did it, so I'm hoping our resident expert will tune in soon.
They say "dose the diet". You adjust your Wararin to match what you consume. Why not a supplement?
I'm thinking of taking Q10, because I'm on statins. Interesting to see what it will do to my INR.

Please read up on Coronary Artery Disease and how we get it. I'd never take calcium supplements though.

 

[Agian]

Cholesterol is just one cause of CAD. There are heaps of others: Diabetes, elevated homocysteine, inflammation, high CRP, high Lipoprotein (a). High LDL, Low HDL, hypertension, even stress, Inflammation makes the blood vessels vulnerable to plaque formation, including smoking, Triglyceride surges after fatty meals etc etc. There are volumes written on this stuff! Kids with FH get CAD in their 30s, so we know lipids are a major cause of plaques. Like I said, first come the fatty streaks, then the plaques, when the plaques mature, they calcify. All we can do is modify our risk factors. Saying Warfarin causes calcification based on some bullshit you read on the net is doing yourself a disservice, when there are literally thousands of studies on the cause of CAD.

Oh, I'd rather not have to take Medication X (be that Warfarin, or whatever). Who wants to take ANY medication?

 

[Agian]

My total cholesterol went down to 1.0 just after surgery, my Lp(a) went from 0.44 to 0.78, my HDL went from 1.3 to 0.6, whilst my platelets went from 74 to over 400. These are called acute phase reactants, post -op. My Hb dropped to 78 and is now creeping up, 114 last time I checked. Since we're talking about numbers. There's science and there's frogshit.

 

[cldlhd]

I'm guessing you'd probably have to increase your dose of Warfarin, but so what?
Pel reckons "gym guy" did it, so I'm hoping our resident expert will tune in soon.
They say "dose the diet". You adjust your Wararin to match what you consume. Why not a supplement?
I'm thinking of taking Q10, because I'm on statins. Interesting to see what it will do to my INR.

Please read up on Coronary Artery Disease and how we get it. I'd never take calcium supplements though.

I have read up on it, maybe not to the extent of some but hey. Some believe the fatty deposits cause calcification theory is pushed by pharmaceutical companies who want everyone on a statin from birth to death. I'm not saying they've set the hook on me with that one but it's out there.

 

[Paleowoman]

I don’t think anyone knows for sure the causes of Coronary Heart Disease. Currently two doctors in the UK are writing good blogs about it. First one, Dr Malcolm Kendrick is on the 19th ‘episode’ https://drmalcolmkendrick.org you’ll have a lot of reading to read them all And second one, Dr David Grimes, who writes a little less often than Dr Kendrick, has a very interesting point of view (microbial/infection): http://www.drdavidgrimes.com

 

[Nocturne]

L

except as I mentioned there is no evidence to support the idea ... there is a heap of people such as dick who have been on it for decades longer than anyone in that survery with no effect

Were any of them in the worst 1% category for CAC? Or even the worst 25%?

If they had and maintained a CAC score of zero, that means that their "windshield never got cracked", so of course the speed at which the crack was going to grow would have been of no consequence.

If they had mild amounts of CAC for their age, and warfarin messing with K2 levels accelerated things enough that the went from the bottom 25% to the mid range when it comes to CAC for their age, over the course of twenty years, maybe they had not much to worry about.

Maybe for MOST people under 65, it's not a big issue and mechanical valves are just the way to go.

But I'm not MOST people. When it comes to CAC, my ship is taking on water and I'm going to be bailing for the rest of my life -- do I really want to risk another hull breach?