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Elevated matrix metalloproteinase-9 associated with stroke or cardiovascular death in patients with carotid stenosis
Nikolaj Eldrup1, Marie-Louise Moes Grønholdt, Henrik Sillesen
1Department of Vascular Surgery, Rigshospitalet, Copenhagen University Hospital, Denmark.
Insights
Elevated matrix metalloproteinase-9 levels in patients with carotid stenosis significantly increase the risk of stroke or cardiovascular death. Combining high matrix metalloproteinase-9 with echolucent plaques further amplifies this risk.
Area of Science:
- Cardiovascular Medicine
- Neurology
- Biochemistry
Background:
- Matrix metalloproteinase-9 (MMP-9) is implicated in atherosclerotic plaque destabilization.
- Carotid stenosis poses a significant risk for cerebrovascular events.
Purpose of the Study:
- To investigate the association between plasma MMP-9 levels and the risk of ipsilateral stroke or cardiovascular death in patients with carotid stenosis.
- To evaluate the combined predictive value of MMP-9 and plaque characteristics on cardiovascular outcomes.
Main Methods:
- Prospective follow-up of 207 patients with >= 50% carotid stenosis.
- Measurement of plasma MMP-9 levels and assessment of carotid plaque echogenicity using B-mode ultrasound.
- Analysis of cumulative incidence and hazard ratios for ipsilateral stroke or cardiovascular death.
Main Results:
- Patients with MMP-9 levels above the median (41.9 ng/mL) had a 1.9-fold increased risk of ipsilateral stroke or cardiovascular death (P=0.002).
- This association remained significant up to 10 years of follow-up.
- Elevated MMP-9 combined with echolucent plaques showed a 4.4-fold increased risk for cardiovascular death and a 3.3-fold increased risk for stroke.
Conclusions:
- Elevated plasma MMP-9 is a significant predictor of adverse cardiovascular events in patients with severe carotid stenosis.
- The combination of high MMP-9 and echolucent plaque morphology substantially increases the risk of stroke and cardiovascular death.
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 > or = 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 > or = 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.
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