MMP-2 Associates With Incident Heart Failure and Atrial Fibrillation: The ARIC Study
Circulation: Heart Failure, 2023
Buckley L., Agha A., Dorbala P., Claggett B., Yu B., Hussain A., Nambi V., Chen L., Matsushita K., Hoogeveen R., Ballantyne C., Shah A.
Disease area | Application area | Sample type | Products |
---|---|---|---|
CVD | Pathophysiology | Plasma | Olink Target 96 |
Abstract
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.