TY - JOUR
T1 - MMP-2 Associates With Incident Heart Failure and Atrial Fibrillation
T2 - The ARIC Study
AU - Buckley, Leo F.
AU - Agha, Ali M.
AU - Dorbala, Pranav
AU - Claggett, Brian L.
AU - Yu, Bing
AU - Hussain, Aliza
AU - Nambi, Vijay
AU - Chen, Lin Yee
AU - Matsushita, Kunihiro
AU - Hoogeveen, Ron C.
AU - Ballantyne, Christie M.
AU - Shah, Amil M.
N1 - Publisher Copyright:
© 2023 American Heart Association, Inc.
PY - 2023/11/1
Y1 - 2023/11/1
N2 - 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.
AB - 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.
KW - atrial fibrillation
KW - echocardiography
KW - epidemiology
KW - heart failure
KW - matrix metalloproteinases
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U2 - 10.1161/CIRCHEARTFAILURE.123.010849
DO - 10.1161/CIRCHEARTFAILURE.123.010849
M3 - Article
C2 - 37753653
AN - SCOPUS:85178542579
SN - 1941-3289
VL - 16
SP - E010849
JO - Circulation: Heart Failure
JF - Circulation: Heart Failure
IS - 11
ER -