Published Online
on October 9, 2006

A more recent version of this article appeared on October 24, 2006

This Article Full Text (PDF) CME: Take the course for this article: Circulation: October 24, 2006, Volume 114, Number 17 All Versions of this Article: 114/17/1847    most recent CIRCULATIONAHA.105.593483v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Eldrup, N. Articles by Nordestgaard, B. G. Search for Related Content PubMed PubMed Citation Articles by Eldrup, N. Articles by Nordestgaard, B. G. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Medline Plus Health Information Stroke Related Collections Pathophysiology Risk Factors Carotid Stenosis Related Article

Submitted on October 7, 2005
Revised on August 4, 2006
Accepted on August 29, 2006

Elevated Matrix Metalloproteinase-9 Associated With Stroke or Cardiovascular Death in Patients With Carotid Stenosis

Nikolaj Eldrup MD, Marie-Louise Moes Grønholdt MD, PhD, DMSc, Henrik Sillesen MD, DMSc, and Børge G. Nordestgaard MD, DMSc^*

From the Department of Vascular Surgery, Rigshospitalet, Copenhagen University Hospital (N.E., M.-L.M.G., H.S.) and Department of Clinical Biochemistry, Herlev University Hospital, University of Copenhagen (N.E., B.G.N.), Copenhagen, Denmark.

^* To whom correspondence should be addressed. E-mail: brno{at}herlevhosp.kbhamt.dk.

Background--Matrix metalloproteinase-9 could exhibit an important role in the destabilization of atherosclerotic carotid plaques. We hypothesized that in patients with carotid stenosis, elevated levels of plasma matrix metalloproteinase-9 are associated with ipsilateral stroke or cardiovascular death.

Methods and Results--We followed up 207 patients with 50% carotid stenosis initially for a mean of 4.4 years, during which time 53 patients developed ipsilateral stroke or died of cardiovascular causes. The cumulative incidence of ipsilateral stroke or cardiovascular death was higher in those with matrix metalloproteinase-9 above versus below the median of 41.9 ng/mL (log-rank P=0.002). Matrix metalloproteinase-9 above versus below the median had a hazard ratio for ipsilateral stroke or cardiovascular death of 1.9 (95% confidence interval [CI], 1.1 to 3.5); during extended follow-up, this remained significant until 10 years. The absolute risk of ipsilateral stroke or cardiovascular death at 4.4 years was 34% and 17% in those with matrix metalloproteinase-9 above and below the median, respectively. Elevated matrix metalloproteinase-9 and an echolucent plaque on B-mode ultrasound versus a low matrix metalloproteinase-9 and an echorich plaque had a hazard ratio for ipsilateral stroke or cardiovascular death of 4.4 (95% CI, 1.8 to 11.1) and for ipsilateral stroke of 3.3 (95% CI, 1.1 to 9.7).

Conclusions--Elevated levels of matrix metalloproteinase-9 in patients with 50% carotid stenosis were associated with a 2-fold risk of ipsilateral stroke or cardiovascular death. Combining elevated matrix metalloproteinase-9 and plaque echolucency was associated with a 4-fold risk for ipsilateral stroke or cardiovascular death and a 3-fold risk for ipsilateral stroke.

Key words: atherosclerosis • carotid artery diseases • matrix metalloproteinases

Related Article:

Issue Highlights
Circulation 2006 114: 1793. [Extract] [Full Text]

This article has been cited by other articles:

				S. Fujimoto, D. Hartung, S. Ohshima, D. S. Edwards, J. Zhou, P. Yalamanchili, M. Azure, A. Fujimoto, S. Isobe, Y. Matsumoto, et al. Molecular Imaging of Matrix Metalloproteinase in Atherosclerotic Lesions: Resolution With Dietary Modification and Statin Therapy J. Am. Coll. Cardiol., December 2, 2008; 52(23): 1847 - 1857. [Abstract] [Full Text] [PDF]

				P. Welsh, P.H. Whincup, O. Papacosta, S.G. Wannamethee, L. Lennon, A. Thomson, A. Rumley, and G.D.O. Lowe Serum matrix metalloproteinase-9 and coronary heart disease: a prospective study in middle-aged men QJM, October 1, 2008; 101(10): 785 - 791. [Abstract] [Full Text] [PDF]

				R. R. S. Packard and P. Libby Inflammation in Atherosclerosis: From Vascular Biology to Biomarker Discovery and Risk Prediction Clin. Chem., January 1, 2008; 54(1): 24 - 38. [Abstract] [Full Text] [PDF]