Fibrosis-related biomarkers and risk of total and cause-specific mortality

Isha Agarwal, Nicole L. Glazer, Eddy Barasch, Mary L. Biggs, Luc Djoussé, Annette L. Fitzpatrick, John S. Gottdiener, Joachim H. Ix, Jorge Kizer, Eric B. Rimm, David S. Siscovick, Russell P. Tracy, Susan J. Zieman, Kenneth J. Mukamal

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Fibrosis has been implicated in diverse diseases of the liver, kidney, lungs, and heart, but its importance as a risk factor for mortality remains unconfirmed. We determined the prospective associations of 2 complementary biomarkers of fibrosis, transforming growth factor-β (TGF-β) and procollagen type III N-terminal propeptide (PIIINP), with total and cause-specific mortality risks among community-living older adults in the Cardiovascular Health Study (1996-2010). We measured circulating TGF-β and PIIINP levels in plasma samples collected in 1996 and ascertained the number of deaths through 2010. Both TGF-β and PIIINP were associated with elevated risks of total and pulmonary mortality after adjustment for sociodemographic, clinical, and biochemical risk factors. For total mortality, the hazard ratios per doubling of TGF-β and PIIINP were 1.09 (95% confidence interval (CI): 1.01, 1.17; P = 0.02) and 1.14 (CI: 1.03, 1.27; P = 0.01), respectively. The corresponding hazard ratios for pulmonary mortality were 1.27 (CI: 1.01, 1.60; P = 0.04) for TGF-β and 1.52 (CI: 1.11, 2.10; P = 0.01) for PIIINP. Associations of TGF-β and PIIINP with total and pulmonary mortality were strongest among individuals with higher C-reactive protein concentrations (P for interaction < 0.05). Our findings provide some of the first large-scale prospective evidence that circulating biomarkers of fibrosis measured late in life are associated with death.

Original languageEnglish (US)
Pages (from-to)1331-1339
Number of pages9
JournalAmerican Journal of Epidemiology
Volume179
Issue number11
DOIs
StatePublished - Jun 1 2014

Fingerprint

Collagen Type III
Transforming Growth Factors
Fibrosis
Biomarkers
Mortality
Confidence Intervals
Lung
Kidney Diseases
C-Reactive Protein
Liver Diseases
Health

Keywords

  • biomarkers
  • fibrosis
  • inflammation
  • mortality

ASJC Scopus subject areas

  • Epidemiology

Cite this

Agarwal, I., Glazer, N. L., Barasch, E., Biggs, M. L., Djoussé, L., Fitzpatrick, A. L., ... Mukamal, K. J. (2014). Fibrosis-related biomarkers and risk of total and cause-specific mortality. American Journal of Epidemiology, 179(11), 1331-1339. https://doi.org/10.1093/aje/kwu067

Fibrosis-related biomarkers and risk of total and cause-specific mortality. / Agarwal, Isha; Glazer, Nicole L.; Barasch, Eddy; Biggs, Mary L.; Djoussé, Luc; Fitzpatrick, Annette L.; Gottdiener, John S.; Ix, Joachim H.; Kizer, Jorge; Rimm, Eric B.; Siscovick, David S.; Tracy, Russell P.; Zieman, Susan J.; Mukamal, Kenneth J.

In: American Journal of Epidemiology, Vol. 179, No. 11, 01.06.2014, p. 1331-1339.

Research output: Contribution to journalArticle

Agarwal, I, Glazer, NL, Barasch, E, Biggs, ML, Djoussé, L, Fitzpatrick, AL, Gottdiener, JS, Ix, JH, Kizer, J, Rimm, EB, Siscovick, DS, Tracy, RP, Zieman, SJ & Mukamal, KJ 2014, 'Fibrosis-related biomarkers and risk of total and cause-specific mortality', American Journal of Epidemiology, vol. 179, no. 11, pp. 1331-1339. https://doi.org/10.1093/aje/kwu067
Agarwal I, Glazer NL, Barasch E, Biggs ML, Djoussé L, Fitzpatrick AL et al. Fibrosis-related biomarkers and risk of total and cause-specific mortality. American Journal of Epidemiology. 2014 Jun 1;179(11):1331-1339. https://doi.org/10.1093/aje/kwu067
Agarwal, Isha ; Glazer, Nicole L. ; Barasch, Eddy ; Biggs, Mary L. ; Djoussé, Luc ; Fitzpatrick, Annette L. ; Gottdiener, John S. ; Ix, Joachim H. ; Kizer, Jorge ; Rimm, Eric B. ; Siscovick, David S. ; Tracy, Russell P. ; Zieman, Susan J. ; Mukamal, Kenneth J. / Fibrosis-related biomarkers and risk of total and cause-specific mortality. In: American Journal of Epidemiology. 2014 ; Vol. 179, No. 11. pp. 1331-1339.
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