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

Abstract

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- β (TGF-β), 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-β (n=1371) and PIIINP (n=2568) from plasma samples collected in 1996 and ascertained events through 2010. Given TGF-β'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-β 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-β has a stronger fibrogenic effect in the setting of inflammation is warranted.

• Authors: 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
• Journal: Circulation. Arrhythmia and electrophysiology (Circ Arrhythm Electrophysiol) Vol. 7 Issue 4 Pg. 583-9 (Aug 2014) ISSN: 1941-3084 [Electronic] United States
• PMID: 24963008 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)
• Copyright: © 2014 American Heart Association, Inc.

Chemical References

• Biomarkers
• Peptide Fragments
• Procollagen
• Transforming Growth Factor beta
• procollagen Type III-N-terminal peptide
• C-Reactive Protein

Topics

• Age Factors
• Aged
• Aged, 80 and over
• Aging (blood)
• Biomarkers (blood)
• C-Reactive Protein (analysis)
• Cardiovascular Diseases (blood, epidemiology, pathology)
• Female
• Fibrosis
• Heart Failure (blood, epidemiology, pathology)
• Humans
• Incidence
• Male
• Myocardial Infarction (blood, epidemiology, pathology)
• Peptide Fragments (blood)
• Procollagen (blood)
• Prognosis
• Prospective Studies
• Risk Assessment
• Risk Factors
• Stroke (blood, epidemiology, pathology)
• Time Factors
• Transforming Growth Factor beta (blood)
• United States (epidemiology)