Background:
Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in cardiac remodeling through regulation of extracellular matrix. Reports on their association with heart failure (HF) outcomes have been conflicting.
Methods:
We prospectively examined the association of baseline serum levels of MMP‐1, ‐2, and ‐9 and TIMP‐1, ‐2, ‐3, and ‐4 with outcomes (death, cardiac transplantation, left ventricular assist device implantation, or HF hospitalization) in 147 stable outpatients with HF from January 2008 to July 2009. Levels of MMPs and TIMPs were measured by Fluorokine MAP Human MMP and TIMP kits.
Results:
Mean age of patients was 56.5 ± 12 years, 66.7% were male, 57.8% were white, and 36.7% were black. Mean left ventricular ejection fraction was 24.6% ± 11%. During a mean follow‐up of 23.4 ± 6.7 months, 49 patients (33%) experienced an outcome event. MMP‐2 (239 ± 76 vs. 286 ± 78 ng/mL, P = 0.01) and TIMP‐2 (119 ± 20 vs. 133 ± 22 ng/mL, P = 0.01) were significantly higher in patients with events. MMP‐2 and TIMP‐2 had an area under the curve of 0.68 ± 0.05 and 0.71 ± 0.05 for predicting outcomes. TIMP‐2 positively correlated with MMP‐2 (r = 0.77, P < 0.01) and B‐type natriuretic peptide (r = 0.19, P < 0.03) and negatively with ejection fraction (r = 0.26, P < 0.01) and the 6‐minute walk test (r = 0.19, P < 0.03). In Cox models controlling for age, sex, ejection fraction, creatinine, and therapy, only TIMP‐2 level was associated with risk of adverse outcomes (OR, 1.018; 95% CI, 1.005‐1.031, per ng/m; P = 0.005).
Conclusions:
Elevated serum levels of TIMP‐2 were strongly and independently associated with adverse outcomes in this cohort of stable outpatients with primarily systolic HF.
Disclosures:
V. Bhalla ‐ none; V. V. Georgiopoulou ‐ none; A. P. Kalogeropoulos ‐ none; L. Fike ‐ none; G. Giamouzis ‐ none; C. P. Norton ‐ none; S. R. Laskar ‐ none; A. L. Smith ‐ none; J. Butler ‐ none