Kickas.org Forums Ankylosing Spondylitis General Discussion #1 AS Web Support Group statins for AS?

Did anyone else notice an article about cholesterol lowering statins having a positive effect on RA (and I suppose by extension AS)? I came across the info when I was in Sacramento, but didn't save the article and haven't seen any more about it.

Adam Rodman

Hmmmm, what are statins? Are they like plant sterols? probably not..

anyways, found a medical journal article on PubMed using the keywords "arthritis statin" :


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Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site.
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Nat Med 2001 Jun;7(6):687-92 Related Articles, Links
Weitz-Schmidt G, Welzenbach K, Brinkmann V, Kamata T, Kallen J, Bruns C, Cottens S, Takada Y, Hommel U.
Novartis Pharma AG, Preclinical Research, Basel, Switzerland. gabrielle.weitz@pharma.novartis.com

The beta2 integrin leukocyte function antigen-1 (LFA-1) has an important role in the pathophysiology of inflammatory and autoimmune diseases. Here we report that statin compounds commonly used for the treatment of hypercholesterolemia selectively blocked LFA-1-mediated adhesion and costimulation of lymphocytes. This effect was unrelated to the statins' inhibition of 3-hydroxy-3-methylglutaryl coenzyme-A reductase; instead it occurred via binding to a novel allosteric site within LFA-1. Subsequent optimization of the statins for LFA-1 binding resulted in potent, selective and orally active LFA-1 inhibitors that suppress the inflammatory response in a murine model of peritonitis. Targeting of the statin-binding site of LFA-1 could be used to treat diseases such as psoriasis, rheumatoid arthritis, ischemia/reperfusion injury and transplant rejection.

PMID: 11385505 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11385505&dopt=Abstract
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This one briefly mentions statins possible anti-inflammatory properties:
http://my.webmd.com/encyclopedia/article/1809.51304

Excellent article on statin and Alzheimers (unrelated obviously) :
http://my.webmd.com/content/article/1809.52340

"So long and thanks for all the fish" - Hitch Hikers Guide To The Galaxy

You found the right articles. Statins are a class of cholesterol lowering drugs that have been enormously effective and are a standard prescription for people with any kind of coronary artery disease.

Adam Rodman

Isn't that curious. I am on Lipitor, a statin drug, to lower my cholesterol, and it is working well for that purpose. Come to think of it, my AS has been much better since I have been on the Lipitor. Maybe there is something to this. I'm glad I have the Lipitor. My doctor is probably significantly extending my life by placing me on it.

Val.

I should have bolded the conclusion, since I doubt anyone would bother reading the gibberish all the way to the end.

"Targeting of the statin-binding site of LFA-1 could be used to treat diseases such as psoriasis, rheumatoid arthritis, ischemia/reperfusion injury and transplant rejection."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11385505&dopt=Abstract



"So long and thanks for all the fish" - Hitch Hikers Guide To The Galaxy

I will have to get my doctor to perscribe a statin drug :-) I wonder which ones would work best?

If you have a high LDL (low densitiy lipoprotein) and a high CRP (C reactive protein) gives you a high risk of coronary artery disease (CAD). so we probably should be on statins anyway :-) (eg: lipitor) take note: Having a high LDL and a high CRP almost doubles your risk. I would bet all us AS'ers have high CRP's, and a good number of high LDL's.


BTW, There was a scientific american article about the link of gingivitis leading to elevated CRP (C reactive protein) . High CRP is a risk factor in heart disease. Therefore gingivitis could be associated with heart disease !
http://www.sciam.com/article.cfm?articleID=0002DB6D-1B78-1C70-84A9809EC588EF21&pageNumber=1&catID=2

Question: Do women (supposedly) have milder AS symptoms due to lower LDL CRP values.

Question 2: If I lower my LDL CRP levels, will my symptoms be milder

So I guess the plan know is to brush my teeth, then start taking Lipitor :-)


"So long and thanks for all the fish" - Hitch Hikers Guide To The Galaxy

Try going on pubmed and searching for statin - as there are so many articles I dont have time to read them all !

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=&DB=PubMed
try these searches:
statin inflammation
statin arthritis
statin
the first one has 76 articles, some of which are interesting.

"So long and thanks for all the fish" - Hitch Hikers Guide To The Galaxy

This thread does certainly seemed to have hitched a ride out into orbit. I think what happens is LFA-1 is a molecule that enables leukocytes in the blood stream to hitch themselves onto the endothelium of blood vessels and then subsequently pass through to reach damaged tissue (trauma, infection etc). That is, it is part of the immune system, and this proposed drug that will stop it working is essentially another kind of immunosuppressant. And maybe drugs which stop leukocytes hitching on will also stop the cholesterol doing the same as well, and vice versa? According to a Medscape article when cholesterol particles adhere to the endothelial wall they increase permeability. If this is so then perhaps that could aid the autoimmune activity by allowing more leukocytes to cross over, hence the reported improvement in AS symptoms above when statins are used.

They also serve who have to use a straw

Edited by bilko on 10/30/02 08:14 AM (server time).

thanx for that bilko!

here is another abstract:
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"However, an increasing number of in vitro and in vivo studies indicate that statins have direct anti-inflammatory effects that are not mediated by their hypocholesterolemic activity."
"mechanisms by which statins might affect leukocyte adhesion and migration to sites of inflammation are reviewed"

Trends Pharmacol Sci 2002 Oct;23(10):482
Statins as anti-inflammatory agents.
PMID: 12368073 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12368073&dopt=Abstract

"So long and thanks for all the fish" - Hitch Hikers Guide To The Galaxy

This abstract relates to my comment on CRP's earlier and their relation to heart disease. I saw an excellent explanation of this in a Scientific American magazine.. but I cant find it, darn....

** "The acute-phase reactant C-reactive protein (CRP) has been shown to reflect systemic and, perhaps, vascular inflammation and to predict future cardiovascular events in asymptomatic individuals."...
"Statin class drugs and aspirin appear to modulate CHD risk in those with increased hs-CRP concentration. "

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Cardiovasc Toxicol 2001;1(2):153-7
C-reactive protein and coronary heart disease: diagnostic and therapeutic implications for primary prevention.

Rifai N.
Department of Laboratory Medicine, Children's Hospital and Harvard Medical School, Boston MA 02115, USA. Rifai@tch.harvard.edu

Coronary heart disease (CHD) is the leading cause of death in the industrialized world. Recent laboratory and clinical studies have shown that inflammation plays a pivotal role in the inception, progression, and destabilization of atheromas. The acute-phase reactant C-reactive protein (CRP) has been shown to reflect systemic and, perhaps, vascular inflammation and to predict future cardiovascular events in asymptomatic individuals. The relative risk associated with CRP is independent of other cardiovascular disease risk factors. High-sensitivity assays (hs-CRP) are needed for the measurement of CRP concentration for the purpose of predicting the risk of future coronary events. Available assays must be standardized because patients' results will be interpreted using population-based cutpoints. An algorithm for risk stratification incorporating hs-CRP and total cholesterol to high-density lipoprotein cholesterol ratio has been developed. Statin class drugs and aspirin appear to modulate CHD risk in those with increased hs-CRP concentration. Several prospective studies are now underway to specifically develop novel clinical utilities and therapeutic strategies for hs-CRP.

Publication Types:
Review
Review, Tutorial
PMID: 12213988 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12213988&dopt=Abstract


"So long and thanks for all the fish" - Hitch Hikers Guide To The Galaxy