Take Losartan/Cozaar for BAV with aneurysm, says expert

[Maryka]

Johns Hopkins Hospital lecture by expert geneticist, Hal Dietz, yesterday was very enlightening! The animal studies all show that Losartan/Cozaar turns around damage done by the faulty genes in Marfan Syndrom. The Human studies are still continuing, but look very promising. (Marfan Syndrome is so rare, it has taken awhile to get the number of subjects they need.)

I have been taking Cozaar for a few years, but since my diagnosis changed to Bicuspid Aortic Valve disorder from Marfan Syndrome, I wondered if I should still take it. I also am forced to pay totally out-of-pocket for my Cozaar (100 dollars a month) by my delightful medical insurance, so I am very motivated to switch meds, if possible. So, I asked Hal Dietz during the open audience question-and-answer period if I, not being "Marfan" anymore, could stop taking Cozaar.

Hal Dietz said "Take it!" because: He has looked at the tissue slides from people with BAV combined with an aortic aneurysm and their tissue abnormalities are very similar to Marfan abnormailites, so his educated opinion is that people with BAV+aneurysm should take Losartan/Cozaar. (People with BAV and NO aneurysm would not necessarily benefit, however.)

In Marfan people, Losartan/Cozaar helps normalize tissues in the following trouble areas: Heart valve, aorta, lungs (as in emphysema), and muscles (as in genetic Marfan weakness). (I am sorry that I forgot whether it helps Marfan eye problems, but I think it does.)

As for my high cost of Losartan/Cozaar, Hal Dietz said that generic versions of Losartan will be marketed within a month or two, so that should help me.

 

[Ross]

As for my high cost of Losartan/Cozaar, Hal Dietz said that generic versions of Losartan will be marketed within a month or two, so that should help me.

Man I hope so, Losartan ain't cheap. I've been waiting and waiting for wait seems like forever.

 

[Fundy]

In Marfan people, Losartan/Cozaar helps normalize tissues in the following trouble areas: Heart valve, aorta, lungs (as in emphysema), and muscles (as in genetic Marfan weakness).

What would normalize mean in terms of heart valve,lungs?
Preventing further deterioration or reversing it?

Any discussions by Dietz on contra-indications for stuff like caffeine, alcohol, and tobacco. I've found those often listed in discussions concerning Marfans and other ctds. Just wondering if they remain contra-indicated if Losartan working as expected.

Why is it that your medical insurance wouldn't cover Losartan?

At what point pre-aortic root replacement did you begin taking Losartan, I think you mentioned previously that it didn't seem to help at all in that respect. I'm wondering how quickly the drug is theorized to work. such as x amount of time to begin rebuilding process and y amount of time to complete.

I'm also wondering about Marfan people with BAV, is that thought to be part of the genetic Marfan defect or is it a defect in another gene which accompanies Marfan gene defect alot. Put it another way, is the BAV of myself and the BAV of a Marfan caused by the same gene defect, or is the BAV caused by defects in separate genes.

and in regard to the reference about muscles (Marfan weakness). I've searched alot of articles on ctds looking for named disorders that had muscle symptoms, but it seemed to me that Turners was the only one with any consistancy of being mentioned. Although I've seen it mentioned that tight muscles may be the result of weak/loose tendons and compensating for that fact in many disorders. I don't recall weak muscles being mentioned at all I don't think.

Just wondering if you have any thoughts or links to others thoughts on this. I've found dietary changes such as no coffee,pop, beef, to help a lot with regard to my muscle problems. Being male and not mentally handicapped, I doubt Turner's would apply in my case. What type of side effects accompany Losartan use, is muscle tightness is one of them.

Have you seen any web presentations of his lectures on Losartan studies available?

 

[Maryka]

I am not sure if I can address all of your questions right here because, well, I was not really taking notes. The Dietz Losartan research project is still going on, so I am not sure what is published officially yet. I will research some of this on Google and get back to this forum. (Right now I am fighting a horribly painful hip problem which you could read about on the Antigoagulation thread. However, that will hopefully be "fixed" next week.)

Here is what I saw in the presentation given by Hal Dietz: There were lots of photos of Marfan people and their various geneticly caused problems (more on the muscle issue later). There were lots of photos of mice bred to have Marfan syndrome problems (yucky, but impressive). There were lots of photos of slides of tissues from various organs in Marfan people and Marfan mice. There were lots of photos of normal (non-marfan) people's tissue slides and pictures of normal ("wild type") mouse tissue slides. The differences in the "normal" tissues and the marfan tissues were striking. The key difference is something called an abnormal substance called TGFBeta. (I could have the initials wrong, but I think I got it right. This TGFBeta is produced in Marfan people and not normal people. In the past we all believed that Marfan people were born with a lack of connective tissue, but it now appears that this TGFBeta produced in Marfan people DESTROYS important connective tissue and, the longer a Marfan person survives, the greater the damage caused by TGFBeta. There are great variations in the amount of TGFBeta produced by various people with Marfan. (Marfan seems to have unique variations from family to family. That is why you cannot easily diagnose it from blood analysis as you can from say, Turners Syndrome.) Although Dietz did not emphasize it in his talk, it seems to me that the longer it takes to start taking Losartan (and the hundreds of other drugs pharmaceutical companies are waiting to roll out), the more irreparable damage is done. This is MY take on it. Still, Marfan damage is ongoing over the life of the afflicted, so anything to lessen future damage is worth doing. But, all things considered, Losartan looks like it would be best administered to children continuously so they do not have so much damage over time.

Muscle problems with Marfan: If your have ever seen a Marfan person in person or photographs of marfan people, you will see they have scrawny limbs. Even doing muscle building exercises will not build normal muscles for marfan people. This, as with all the other Marfan problems, seems to be tied to that TGFBeta stuff attacking the development of muscles. Could a Marfan individual on Losartan become a muscle bound superman in the future? This was not addressed by Dietz and no one asked because, let's face it, Marfan people are mostly concerned with staying alive. Having big muscles would only be icing on the cake-of-life.

As for giving up all of those items you mention, well, I never heard Dietz mention those things, but, maybe he would say that. I, myself, am a vegetarian by conscionce and do not have much of the other things you mentioned. On the other hand, Marfan groups usually serve soft drinks, caffeine rich drinks, sugar-filled treats and other not-so-good foods/drinks. I have seen smoking Marfan people, although, with the propensity of emphysema and other lung disorders, this is not good. (I have never smoked) Vincent Sciavelli (spelling?), the famous Marfan actor overcame many of his Marfan ailments through surgery but died, ultimately, of lung cancer from his smoking addiction.

I only started taking Losartan about four years ago. One of Dietz's early lectures on Losartan mentioned that Losartan may actually greatly help various other genetic disorders, including a form of Muscular Dystrophy. I came away thinking that since I must always take a blood pressure drug anyway, why not switch to Losartan? At last week's lecture, however, I notice that Dietz dropped all mention of other disorders helped by Losartan. He is not yet finished with the Marfan people studies yet (mostly because there are so few Marfan people out there). Other uses of this class of drug will no doubt follow, but that is years away.

So, on Dietz's advice I will continue on Losartan, but, although my aneurysm stopped growing and maybe even shrank a little before my OHS, I did progress with my BAV damage despite taking Losartan. But, from looking at his slides, I see the biggest gains from Losartan are made in the very young, before all of the terrible defects start. (Gee! I had better post this before this new blog times me out again!)

 

[Maryka]

Fundy: Rereading your questions, I think the issue is not which basic bad gene we are born with , but the creation of that TGFBeta substance which attacks various parts of the tissues creating our bodies. I think bicuspid aortic valves are present at birth, even if unrecognized for years or even decades (in my case). The next question: Can scientists test for TGFBeta in our blood? This I do not know. That test in newborns could result in their overcoming the bad effects of TGFBeta and becoming "normal". For us who already falling apart, Losartan can only slow down the damage already happening. (I saw animal photos and tissue slides showing how damage could be somewhat reversed in the circulatory system of mice and their life spans be increased almost to the normal level. Still, starting treatment at birth would have prevented the problems altogether, it appears.)

 

[Maryka]

OK. I see some of the things in the top sticky of this area have some good references. Below are some links I found that make reference to TGF-beta in their discussions:

Apparently what I was describing as "TGFBeta substance" is really a mutation in the T(oops forgot this part) Growth Factor beta receptor.

I found the current Wikipedia entry on Marfan Syndrome is useful in explaining this.

The following articles are useful:
"Aneurysm Syndromes Caused by Mutations in the TGF-beta Receptor"
(Mostly about the Loeys–Dietz syndrome)
In the New England Journal of Medicine , August 24, 2006 (one person in test had a Bicuspid aortic valve)

Also in that issue (above) is "Marfan’s Syndrome and Related Disorders—More Tightly Connected Than We Thought" by Bruce D. Gelb, M.D.
(You need to be a subscriber to read the whole aricles in the New England Journal of Medicine.)

Another helpful link:
http://www.genetics.uab.edu/Education/Graduate/Genomics09-14-05.pdf

Help, someone! We probably need a (more comprehensive) sticky on TBF-Beta!