Abstract 19401: Increased Levels of Tissue Inhibitor of Metalloproteinase 1 Are Independently Associated with Adverse Outcomes in Outpatients with Heart Failure
Introduction: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in cardiac remodeling through regulation of extracellular matrix. However, reports on their association with heart failure (HF) outcomes have been conflicting.
Methods: We examined the association of baseline serum levels of MMP 1, 2, 3, and 9 and TIMP 1, 2, 3, and 4 with outcomes (death, cardiac transplantation, left ventricular assist device implantation, or hospitalization for any cause) in 147 stable outpatients with HF who were enrolled in a prospective HF cohort study in the greater metropolitan Atlanta, GA area from 1/2008 to 7/2009. Levels of MMPs and TIMsP were measured by Fluorokine MAP Human MMP and TIMP Kits.
Results: Mean age of patients was 57.1±12.0 years; 66.7% were male; 58.2% were white and 35.6% black; 41.5% had established coronary artery disease (CAD) and 33.3% had diabetes; 43.5% had a biventricular pacemaker +/− defibrillator. Mean left ventricular ejection fraction was 37.4±13.3%. On follow-up (median: 20 months; IQR: 18–22 months), 52 of 147 patients (35.4%) experienced an event. Table 1 presents the serum levels of MMPs and TIMPs in the total cohort and according to event status. In time-to-event (Cox) models, levels of TIMP-1 (likelihood ratio [LR] chi-square=9.70; p=0.002) and TIMP-2 (LR chi-square=4.81; p=0.028) were positively associated with risk of adverse outcomes, while MMP-1 had a bimodal, inverse U-shape association with outcomes (LR chi-square=9.77; p=0.008). In Cox models controlling for age, gender, race, diabetes, CAD, serum creatinine, and ejection fraction, only baseline TIMP-1 levels were still associated with risk of adverse outcomes (HR per 0.1 ng/mL: 2.19; 95% CI: 1.08–4.47; p=0.031).
Conclusions: Elevated serum levels of TIMP-1 were strongly associated with adverse outcomes in this cohort of stable outpatients with primarily systolic HF; this association was independent of major clinical determinants of outcomes.
- © 2010 by American Heart Association, Inc.