Matrix metalloproteinase 2 (MMP-2) and cardiovascular events in atrial fibrillation patients: A nested case control study from the ATHERO-AF cohort

: Atrial fibrillation (AF) is associated with an increased risk of major adverse cardiovascular events (CVEs) including myocardial infarction, ischemic stroke and peripheral arterial ischemic events despite optimal anticoagulant therapy. Matrix metalloproteinase 2 (MMP-2) levels have been associated with endothelial dysfunction and atherosclerosis, and in AF patients, MMPs seem to play a role in atrial fibrosis but no solid data on the association with CV risk do exist. We measured MMP-2 plasma levels, and its selective naturally occurring inhibitor TIMP-2 in 211 AF patients with (n = 86) or without (n = 125) CVEs, in a nested case-control study from the prospective ATHERO-AF study. The two groups were balanced for clinical characteristics. The median value of MMP-2 was 731 ng/ml in patients with and 953 ng/ml in patients without CVEs (p < 0.05). ROC curve analysis identified a cut-off value of 825 ng/ml associated with CVEs. Patients with MMP-2 above this level had a lower incidence of CVEs (OR: 0.38, CI 0.2-0.6) and stroke (OR 0.37 CI 0.1-0.9). Additionally, multivariable Cox proportional hazards analysis confirmed an inverse association between high levels of MMP-2, CVEs and stroke (HR 0.563, 95%CI 0.358-0.886, p = 0.013 and HR 0.335, 95%CI 0.146-0.771, p = 0.010, respectively). Results were confirmed using continuous values. These data suggest a possible protective role of MMP-2 against CVEs occurrence in patients with AF and highlight the need of further investigations on the potential role of MMP-2 as a prognostic biomarker in non-valvular AF.