MMP-2 Associates With Incident Heart Failure and Atrial Fibrillation: The ARIC Study

Leo F. Buckley, Ali M. Agha, Pranav Dorbala, Brian L. Claggett, Bing Yu, Aliza Hussain, Vijay Nambi, Lin Yee Chen, Kunihiro Matsushita, Ron C. Hoogeveen, Christie M. Ballantyne, Amil M. Shah

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


BACKGROUND: MMP (matrix metalloproteinase)-2 participates in extracellular matrix regulation and may be involved in heart failure (HF), atrial fibrillation (AF), and coronary heart disease. METHODS: Among the 4693 ARIC study (Atherosclerosis Risk in Communities) participants (mean age, 75±5 years; 42% women) without prevalent HF, multivariable Cox proportional hazard models were used to estimate associations of plasma MMP-2 levels with incident HF, HF with preserved ejection fraction (≥50%), HF with reduced ejection fraction (<50%), AF, and coronary heart disease. Mediation of the association between MMP-2 and HF was assessed by censoring participants who developed AF or coronary heart disease before HF. Multivariable linear regression models were used to assess associations of MMP-2 with measures of left ventricular and left atrial structure and function. RESULTS: Compared with the 3 lower quartiles, the highest MMP-2 quartile associated with greater risk of incident HF overall (adjusted hazard ratio, 1.48 [95% CI, 1.21–1.81]), incident HF with preserved ejection fraction (1.44 [95% CI, 1.07–1.94]), incident heart failure with reduced ejection fraction (1.48 [95% CI, 1.08–2.02]), and incident AF (1.44 [95% CI, 1.18–1.77]) but not incident coronary heart disease (0.97 [95% CI, 0.71–1.34]). Censoring AF attenuated the MMP-2 association with HF with preserved ejection fraction. Higher plasma MMP-2 levels were associated with larger left ventricular end-diastolic volume index, greater left ventricular mass index, higher E/e ratio, larger left atrial volume index, and worse left atrial reservoir and contractile strains (all P<0.001). CONCLUSIONS: Higher plasma MMP-2 levels associate with diastolic dysfunction, left atrial dysfunction, and a higher risk of incident HF and AF. AF is a mediator of MMP-2–associated HF with preserved ejection fraction risk.

Original languageEnglish (US)
Pages (from-to)E010849
JournalCirculation: Heart Failure
Issue number11
StatePublished - Nov 1 2023

Bibliographical note

Publisher Copyright:
© 2023 American Heart Association, Inc.


  • atrial fibrillation
  • echocardiography
  • epidemiology
  • heart failure
  • matrix metalloproteinases

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


Dive into the research topics of 'MMP-2 Associates With Incident Heart Failure and Atrial Fibrillation: The ARIC Study'. Together they form a unique fingerprint.

Cite this