Purpose: Biomarkers matrix metalloproteinase-9, (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1), relate to remodeling of the extracellular matrix. In some disease states, the imbalance of these proteins leads to tissue destruction, proteolysis, and synthesis of cytokines and inflammation. Two intermediate-sized studies indicated that TIMP-1 predicts prognosis. We investigated TIMP-1 levels to predict all-cause mortality in the AGES-Reykjavik Study.
Methods: Participants in this study represent 5721 of the 5764 community-dwelling men and women characterized by the AGES-Reykjavik Study and followed by the Icelandic Heart Association since 1967. We measured TIMP-1 using an ELISA assay in citrate plasma drawn in 2002-2006 in participants and related results to all cause mortality.
Results: At the time of blood sampling, the mean age was 77 years (range 66-98); 58‰ were female; hypertension was treated in 64‰, diabetes was present in 13‰, and 12‰ were active smokers. Of the 5721 participants in the study, 39‰ died with a median follow-up of 8 years.
Kaplan Meier survival analysis showed higher quartiles of TIMP-1 were associated with all-cause mortality (Fig.1 1). Both Kaplan Meier and Cox analyses suggested a potential threshold effect where mortality risk elevates after TIMP-1 levels surpass a threshold. Cox multivariable regression analysis adjusted for the cardiovascular risk factors: age, gender, hypertension, smoking status and diabetes found TIMP-1 had the second highest Wald Chi-square score (after age) in the adjusted model.
Conclusion: The biomarker, TIMP-1, is a strong predictor of all-cause mortality in older community dwelling subjects even after adjusting for cardiovascular risk factors.