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Matrix metalloproteinase 2 (MMP-2) and cardiovascular events in atrial fibrillation patients: A nested case control

Danilo Menichelli1, Emanuela Falcinelli2, Pasquale Pignatelli3

  • 1Department of General Surgery, Surgical Specialty and Anaesthesiology, Sapienza University of Rome, Rome, Italy.

Thrombosis Research
|May 22, 2026
PubMed

Insights

Matrix metalloproteinase 2 (MMP-2) may protect against cardiovascular events in atrial fibrillation (AF) patients. Higher MMP-2 levels were linked to a lower incidence of major adverse cardiovascular events and stroke in AF patients.

Area of Science:

  • Cardiovascular Medicine
  • Biomarkers
  • Proteomics

Background:

  • Atrial fibrillation (AF) increases the risk of major adverse cardiovascular events (CVEs) despite anticoagulation.
  • Matrix metalloproteinase 2 (MMP-2) is implicated in endothelial dysfunction and atherosclerosis, with potential roles in AF-related atrial fibrosis.
  • Limited data exist on MMP-2's association with cardiovascular risk in AF patients.

Purpose of the Study:

  • To investigate the association between plasma levels of MMP-2 and its inhibitor TIMP-2 and the occurrence of CVEs in patients with non-valvular AF.
  • To explore the potential of MMP-2 as a prognostic biomarker for cardiovascular risk in AF.

Main Methods:

  • A nested case-control study was conducted within the prospective ATHERO-AF study, including 211 AF patients.
  • Plasma levels of MMP-2 and TIMP-2 were measured in patients with (n=86) and without (n=125) CVEs.
  • Statistical analyses included ROC curve analysis and multivariable Cox proportional hazards analysis.

Main Results:

  • Median MMP-2 levels were lower in patients with CVEs (731 ng/ml) compared to those without (953 ng/ml) (p < 0.05).
  • An MMP-2 cut-off value of 825 ng/ml identified patients with a lower incidence of CVEs (OR: 0.38) and stroke (OR: 0.37).
  • High MMP-2 levels were inversely associated with CVEs (HR: 0.563) and stroke (HR: 0.335) in multivariable analysis.

Conclusions:

  • These findings suggest a potential protective role for MMP-2 against CVEs in AF patients.
  • MMP-2 warrants further investigation as a prognostic biomarker for cardiovascular risk stratification in non-valvular AF.

Keywords:
Atrial fibrillationCardiovascular eventsMatrix metalloproteinases

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