Referee 1's review (Daniel R. Wagner, MD, PhD):

MMP-9 levels are elevated in patients with CAD. MMP-9 is secreted by macrophages present in coronary plaques and can lead to plaque rupture. MMP-9 is also secreted by neutrophils or macrophages in the myocardium and can lead to remodeling after infarction. The present study investigated peripheral levels of MMP-9 in patients without known CAD but with CV risk factors. It appears that MMP-9 levels increase with the number of CV risk factors.

The findings are interesting and the manuscript is well written. However, there are some concerns:
1. Patients were not studied invasively with cath or IVUS. Therefore, the presence of significant CAD cannot be excluded.
2. Why were TIMP levels only measured in half of the patients?
3. The authors should be more cautious with their overall conclusions. Indeed, it is not possible to conclude from this study that MMP-9 is a biomarker with additive information beyond CRP (for which disease?).
4. The discrepancy with the results from the Framingham study may in part be due the different type of ELISA chosen or to the fact that samples were stored for shorter periods of time in the present study. It is known that MMP-9 is degraded during storage, even at -80C (Rouy D et al. Anal Biochem 2005;338:294-298)

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N.B. These are the comments made by the referee when reviewing an earlier version of this paper. Prior to publication the manuscript has been revised in light of these comments and to address other editorial requirements.