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The biomarker tissue inhibitor of metalloproteinase-1 (TIMP-1) is an independent predictor of all-cause mortality in the AGES-Reykjavik study

Session Novel biomarkers in predicting cardiovascular diseases

Speaker Gina LaRocca

Congress : ESC Congress 2014

  • Topic : coronary artery disease, acute coronary syndromes, acute cardiac care
  • Sub-topic : Acute Coronary Syndromes: Biomarkers
  • Session type : Rapid Fire Abstracts
  • FP Number : 1134

Authors : G Larocca (Bethesda,US), T Aspelund (Reykjavik,IS), M Neely (Durham,US), G Eiriksdottir (Kopavogur,IS), LJ Launer (Bethesda,US), TB Harris (Bethesda,US), V Gudnason (Reykjavik,IS), AE Arai (Bethesda,US)

Authors:
G. Larocca1 , T. Aspelund2 , M. Neely3 , G. Eiriksdottir4 , L.J. Launer5 , T.B. Harris5 , V. Gudnason2 , A.E. Arai1 , 1National Institutes of Health, National Heart, Lung, Blood Institute - Bethesda - United States of America , 2University of Iceland - Reykjavik - Iceland , 3Duke University Medical Center - Durham - United States of America , 4Icelandic Heart Association - Kopavogur - Iceland , 5National Institutes of Health, National Institute on Aging - Bethesda - United States of America ,

Citation:
European Heart Journal ( 2014 ) 35 ( Abstract Supplement ), 204

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.

Figure 1

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