Active matrix metalloproteinases 3 and 9 are independently associated with coronary artery in-stent restenosis.
OBJECTIVE
This study aimed to determine whether plasma levels of active matrix metalloproteinases (MMP) are predictors of in-stent restenosis (ISR) in New Zealand patients treated with bare-metal coronary stents.


METHODS
A group of 152 patients with a history of ISR were compared with 151 symptom free 1-year post-stenting patients (non-ISR). Demographic and angiographic characteristics were collected. Plasma samples were analyzed for the active forms of MMP-1, -2, -3 and -9 as well as tissue inhibitor of metalloproteinases (TIMP-1) using ELISA-based isoform sensitive assays.


RESULTS
Both active MMP-9 and active MMP-3 were independently associated with history of ISR. Elevated levels of both active MMP-3 and -9 had an adjusted odds ratio of 11.8 (95% CI: 4-35, p<0.0001) for association with ISR, with 37% of ISR patients having such levels versus 11% on non-ISR. The addition of both of the MMP biomarkers significantly increased the area under the curve (AUC) of a receiver operator characteristic (ROC) analysis incorporating the significant demographic and angiographic variables (AUC 0.85 versus 0.78, p<0.005).


CONCLUSIONS
Measures of plasma active MMP isoforms appear to be independently associated with ISR, and assessment of multiple MMP markers yields cumulative utility.
Jones
G T
GT
Vascular Research Group, Section of Surgery, University of Otago, Dunedin, New Zealand. greg.jones@otago.ac.nz
Tarr
G P
GP
Phillips
L V
LV
Wilkins
G T
GT
van Rij
A M
AM
Williams
M J A
MJ
D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000295:instrumentation*; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000628:therapy*; D023903:Coronary Restenosis / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000209:etiology; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D019278:Matrix Metalloproteinase 3 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008670:Metals; D008875:Middle Aged; D009520:New Zealand; D016017:Odds Ratio; D011474:Prosthesis Design; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors; D015607:Stents; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D016896:Treatment Outcome
D015415:Biomarkers; D008670:Metals; D019715:Tissue Inhibitor of Metalloproteinase-1; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9