Serum tissue-degrading proteinases and incident cardiovascular disease events

Background: Extracellular matrix-degrading proteinases are upregulated in atherosclerotic lesions and can contribute to subsequent pathological events. In the present nested case-control study, we investigated the association of serum concentrations of matrix metalloproteinases MMP-7, MMP-8, and MMP-13, tissue inhibitor of metalloproteinase-1 (TIMP-1), and neutrophil elastase (NE) with incident cardiovascular disease (CVD) events.

Design: The FINRISK97 cohort included 8090 persons with no history of CVD. During the 10-year follow up, 471 incident CVD cases were ascertained and for them, three individually matched controls (n = 1413) were selected. The CVD events included myocardial infarction, stroke, coronary revascularization, and CVD death.

Results: Compared to the controls, the cases had significantly higher serum mean concentrations of MMP-7, MMP-8, and TIMP-1, as well as MMP-7/TIMP-1 ratio. In multivariate analyses adjusted for CVD risk factors, MMP-7, MMP-8, TIMP-1, and MMP-8/TIMP-1 ratio were associated with the risk for incident CVD: OR 1.16 (95% CI 1.03-1.31), OR 1.13 (95% CI 1.01-1.26), OR 1.16 (95% CI 1.02-1.31), and OR 1.13 (95% CI 1.00-1.27) respectively, per SD-increase of log-transformed unit. The associations, however, attenuated into non-significant after adjusting for C-reactive protein (CRP) concentrations.

Conclusions: MMP-7 and MMP-8, which are upregulated during inflammation, can form a proinflammatory tissue destructive cascade. They can be regarded as risk factors, and thus as potential biomarkers for incident CVD. The balance between these MMPs and their tissue inhibitor may indicate vulnerability to plaque rupture.