Fibrosis-related biomarkers and incident cardiovascular disease in older adults the cardiovascular health study

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

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Background-Fibrotic changes in the heart and arteries have been implicated in a diverse range of cardiovascular diseases (CVD), but whether circulating biomarkers that reflect fibrosis are associated with CVD is unknown. Methods and Results-We determined the associations of 2 biomarkers of fibrosis, transforming growth factor- ß (TGF-ß), and procollagen type III N-terminal propeptide (PIIINP), with incident heart failure, myocardial infarction, and stroke among community-living older adults in the Cardiovascular Health Study. We measured circulating TGF-ß (n=1371) and PIIINP (n=2568) from plasma samples collected in 1996 and ascertained events through 2010. Given TGF-ß's pleiotropic effects on inflammation and fibrogenesis, we investigated potential effect modification by C-reactive protein in secondary analyses. After adjustment for sociodemographic, clinical, and biochemical risk factors, PIIINP was associated with total CVD (hazard ratio [HR] per SD=1.07; 95% confidence interval [CI], 1.01-1.14) and heart failure (HR per SD=1.08; CI, 1.01-1.16) but not myocardial infarction or stroke. TGF-ß was not associated with any CVD outcomes in the full cohort but was associated with total CVD (HR per SD=1.16; CI, 1.02-1.31), heart failure (HR per SD=1.16; CI, 1.01-1.34), and stroke (HR per SD=1.20; CI, 1.01-1.42) among individuals with C-reactive protein above the median, 2.3 mg/L (P interaction <0.05).Conclusions-Our findings provide large-scale, prospective evidence that circulating biomarkers of fibrosis, measured in community-living individuals late in life, are associated with CVD. Further research on whether TGF-ß has a stronger fibrogenic effect in the setting of inflammation is warranted.

Original languageEnglish (US)
Pages (from-to)583-589
Number of pages7
JournalCirculation: Arrhythmia and Electrophysiology
Issue number4
StatePublished - Aug 1 2014
Externally publishedYes


  • Cardiovascular diseases
  • Collagen
  • Epidemiology
  • Heart failure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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