Comparison of matrix metalloproteinase 9 and brain natriuretic peptide as clinical biomarkers in chronic heart failure.
BACKGROUND
Matrix metalloproteinase 9 (MMP-9) may serve as a biomarker of ventricular remodeling in selected populations, but few studies have assessed its performance in clinical practice. We tested MMP-9 as a biomarker of remodeling and predictor of outcomes in a systolic heart failure cohort derived from clinical practice and compared its performance to brain natriuretic peptide (BNP).


METHODS
Plasma MMP-9 and BNP levels were measured in 395 outpatients with systolic heart failure who participated in the Penn Heart Failure Study. We tested for (1) cross-sectional associations between biomarker levels, left ventricular end-diastolic dimension index (LVEDDI), and ejection fraction (EF), and (2) associations between baseline biomarker levels and risk of subsequent cardiac hospitalization or death over 3 years of follow-up.


RESULTS
Matrix metalloproteinase 9 had no significant correlation with LVEDDI (rho = 0.04, P = not significant) or EF (rho = -0.06, P = not significant), whereas BNP showed highly significant correlations (LVEDDI: rho = -0.27, P < .0001; EF: rho = -0.35, P < .0001). In multivariate linear regression models, MMP-9 again showed no significant associations with LVEDDI (P = .6) or EF (P = .14), whereas BNP showed strong independent associations (LVEDDI: P < .001; EF: P = .002). Kaplan-Meier analyses showed no difference in hospital-free survival by baseline MMP-9 tertile (P = .7), whereas higher BNP tertile predicted worse survival (P < .0001). In multivariate Cox models, baseline MMP-9 level did not predict risk of adverse outcome (hazard ratio for log increase 0.98, P = .9), whereas BNP was a significant independent predictor (hazard ratio for log increase 1.15, P = .02).


CONCLUSIONS
Compared to BNP, MMP-9 is a poor clinical biomarker of remodeling and outcome in patients with systolic heart failure derived from clinical practice.
Penn Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Esther E
EE
Vorovich
Shaokun
S
Chuai
Mingyao
M
Li
Justin
J
Averna
Victor
V
Marwin
David
D
Wolfe
Muredach P
MP
Reilly
Thomas P
TP
Cappola
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D004452:Echocardiography; D005260:Female; D054143:Heart Failure, Systolic / Q000097:blood* / Q000175:diagnosis* / Q000000981:diagnostic imaging; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D011237:Predictive Value of Tests; D020257:Ventricular Remodeling
D015415:Biomarkers; D020097:Natriuretic Peptide, Brain; D020780:Matrix Metalloproteinase 9