Abstract 16159: The Biomarker Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) is a Stronger Independent Predictor of All-Cause Mortality Than Other Established Biomarkers in the AGES-Reykjavik Study
Objectives: Biomarkers matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1), relate to remodeling of the extracellular matrix. The imbalance of these proteins leads to tissue destruction, proteolysis, synthesis of cytokines, and inflammation. We therefore, hypothesized that MMP-9 and TIMP-1 would predict all-cause mortality independent of other well-established biomarkers in the AGES-Reykjavik Study (Age Gene/Environment Susceptibility- Reykjavik Study).
Methods: Participants in this study represent 5491 of the 5,764 community-dwelling men and women characterized by the AGES-Reykjavik Study and followed by the Icelandic Heart Association since 1967. We measured MMP-9 and TIMP-1 using an ELISA assay in citrate plasma, creatinine for estimated glomerular filtration rate (eGFR), and serum high sensitivity C-reactive protein (hs-CRP). Multivariable Cox regression was used to evaluate rate ratios for all-cause mortality according to 50th, 75th and 95th percentiles of TIMP-1. Chi-square values were used to compare the relative prognostic strength between TIMP-1 and other covariates to all-cause mortality.
Results: At the time of blood sampling, the mean age was 77 years (range 66-98); 42% were male; hypertension was treated in 64%, diabetes was present in 13%, and 12% were active smokers. Of the participants, 34% died (N=1871) with a median follow-up of 8 years. Among all covariates independently associated with all-cause mortality, the overall effect of TIMP-1 percentiles emerged as the strongest covariate after age (Table 1). Fully adjusted, the upper 5th percentile of TIMP-1 remained at a nearly 3-fold increased risk of dying as compared to the lowest 50th percentile (HR 2.5 (2.2 - 3.0), p<0.0001).
Conclusion: TIMP-1 is independently associated with increased risk of all-cause mortality in older community dwelling subjects and was the strongest biomarker of any studied.
Author Disclosures: G. LaRocca: None. A. Greve: None. T. Aspelund: None. G. Eiriksdottir: None. L.J. Launer: None. T.B. Harris: None. V. Gudnason: None. A.E. Arai: None.
- © 2014 by American Heart Association, Inc.