Fran or Doc, could you please translate!!

[bibbz]

As I also have IHD and I am wanting to ditch the statins could you possibly take a look at this article and explain MMP2-3 and 9 are these figures good or bad.

Initial question: I have a male 60 yr old patient with established IHD who is taking simvastatin. Simvastatin may be causing him side effects. If the simvastatin is stopped to see if his side effects go away. how quickly will his risk of a coronary event rise because of the absence of simvastatin. ( I assume his cholesterol will slowly rise up, but does his risk form being OFF simvastatin rise more quickly, possibly making it a dangerous thing to do )?
Answer:
We were unable to find an evidence based answer to this using Cochrane, Medline or TRIP.

We were hopeful of an answer in a review in Bandolier entitled “Statins and the law of unintended consequences” (1) which looked at “two pieces of evidence which imply that stopping or changing statins could increase vascular risk by about three times.” However, we have been unable to access the first piece of evidence, which is an audit published by letter in the Lancet (2), and the second piece of evidence looks at patients who were taking statins before onset of chest pain for whom the statin was discontinued, which seems of limited relevance to your query (3).

We found a recent primary study on Medline entitled “Effects of simvastatin withdrawal on serum matrix metalloproteinases in hypercholesterolaemic patients” (4):

“Sixty-one consecutive hypercholesterolaemic patients whose lipid profiles had been well controlled by regular simvastatin (20 mg day (-1)) treatment for more than 6 months were enrolled. Statin was discontinued after their lipid profiles reached the treatment goal of the ATP-III guideline. The lipid profiles, serum matrix metalloproteinase (MMP) -2, MMP-3 and MMP-9, tissue inhibitor of MMP and highly sensitive C-reactive protein (hsCRP) levels were measured on the day of simvastatin withdrawal and 120 days later. A further 50 hyperlipidaemia patients who had never received statin treatment (positive control group) and 28 healthy patients with normal lipid profiles (negative control group) were also studied as control groups.”

The study found:

“While the lipid profiles had been normalized, the levels of serum inflammatory markers were still higher in hypercholesterolaemic patients than in the healthy subjects. Up to 120 days after statin withdrawal there was no coronary event, but the lipid profiles and serum hsCRP levels had significantly rebounded in study patients. However, serum MMP-2 and MMP-9 levels remained unchanged and the MMP-3 level was even further reduced after statin withdrawal (115.04 +/- 84.54 vs. 92.71 +/- 66.71 ng mL (-1), P = 0.022). Moreover, the amplitudes of variation (%) of each parameter including MMPs, TIMP, hsCRP and lipid profiles after statin withdrawal were inversely correlated to their respective baseline levels before withdrawal (r = -0.702 to -0.284; P < 0.005).
Conclusions: The effects of short-term discontinuation of statin were different on serum hsCRP and MMPs levels in hypercholesterolaemic patients. While lipid profiles and serum hsCRP level had rebounded the serum MMPs levels were still unchanged, or even reduced, suggesting the prolonged effect of statin treatment, especially on serum MMP-3 level up to 120 days after simvastatin withdrawal. Further work is required to clarify the situation both in terms of these serum markers and clinical effects.”

References

1. “Statins and the law of unintended consequences.” Bandolier, 2003.
(http://www.jr2.ox.ac.uk/bandolier/band113/b113-2.html)
2. Thomas, M. and Mann, J. “Increased thrombotic vascular events after change of statin.” Lancet, 5th Dec 98, 352 (9143), pgs 1830 - 1831.
(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9851392&dopt=Abstract)
3. Heeschen, C. et al. “Withdrawal of statins increases event rates in patients with acute coronary syndromes.” Circulation, 26th March 02, 105 (12), pgs 1446 – 1452.
(http://circ.ahajournals.org/cgi/reprint/105/12/1446)
4. Huang, C. Y. et al. “Effects of simvastatin withdrawal on serum matrix metalloproteinases in hypercholesterolaemic patients.” European journal of clinical investigation, Feb 06, 36 (2), pgs 76 – 84.
(http://www.hubmed.org/display.cgi?uids=16436088

Thanks

Lavinia

[sos_group_owner]

Hi Lavinia,

MMP's are "matrix metalloproteinase".
Info from Wikipedia (great internet resource)

"MMPs are also thought to play a major role on cell behaviors such as cell proliferation, migration (adhesion / dispersion), differentiation, angiogenesis, apoptosis and host defense."

For more info this is the link:

[url]http://en.wikipedia.org/wiki/Matrix_metalloproteinase[/url]

Fran