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 Kizer, Eric B. Rimm, David S. Sicovick, Russell P. Tracy, Kenneth J. Mukamal

Research output: Contribution to journalArticle

19 Citations (Scopus)

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- 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
Volume7
Issue number4
DOIs
StatePublished - Aug 1 2014

Fingerprint

Transforming Growth Factors
Fibrosis
Cardiovascular Diseases
Biomarkers
Collagen Type III
Confidence Intervals
Health
Heart Failure
Stroke
C-Reactive Protein
Myocardial Infarction
Inflammation
Arteries
Research

Keywords

  • Cardiovascular diseases
  • Collagen
  • Epidemiology
  • Heart failure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Medicine(all)

Cite this

Agarwal, I., Glazer, N. L., Barasch, E., Biggs, M. L., Djousse, L., Fitzpatrick, A. L., ... Mukamal, K. J. (2014). Fibrosis-related biomarkers and incident cardiovascular disease in older adults the cardiovascular health study. Circulation: Arrhythmia and Electrophysiology, 7(4), 583-589. https://doi.org/10.1161/CIRCEP.114.001610

Fibrosis-related biomarkers and incident cardiovascular disease in older adults the cardiovascular health study. / Agarwal, Isha; Glazer, Nicole L.; Barasch, Eddy; Biggs, Mary L.; Djousse, Luc; Fitzpatrick, Annette L.; Gottdiener, John S.; Ix, Joachim H.; Kizer, Jorge; Rimm, Eric B.; Sicovick, David S.; Tracy, Russell P.; Mukamal, Kenneth J.

In: Circulation: Arrhythmia and Electrophysiology, Vol. 7, No. 4, 01.08.2014, p. 583-589.

Research output: Contribution to journalArticle

Agarwal, I, Glazer, NL, Barasch, E, Biggs, ML, Djousse, L, Fitzpatrick, AL, Gottdiener, JS, Ix, JH, Kizer, J, Rimm, EB, Sicovick, DS, Tracy, RP & Mukamal, KJ 2014, 'Fibrosis-related biomarkers and incident cardiovascular disease in older adults the cardiovascular health study', Circulation: Arrhythmia and Electrophysiology, vol. 7, no. 4, pp. 583-589. https://doi.org/10.1161/CIRCEP.114.001610
Agarwal, Isha ; Glazer, Nicole L. ; Barasch, Eddy ; Biggs, Mary L. ; Djousse, Luc ; Fitzpatrick, Annette L. ; Gottdiener, John S. ; Ix, Joachim H. ; Kizer, Jorge ; Rimm, Eric B. ; Sicovick, David S. ; Tracy, Russell P. ; Mukamal, Kenneth J. / Fibrosis-related biomarkers and incident cardiovascular disease in older adults the cardiovascular health study. In: Circulation: Arrhythmia and Electrophysiology. 2014 ; Vol. 7, No. 4. pp. 583-589.
@article{f83d84b90a1e4808a1ebbbb056422b29,
title = "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- {\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.",
keywords = "Cardiovascular diseases, Collagen, Epidemiology, Heart failure",
author = "Isha Agarwal and Glazer, {Nicole L.} and Eddy Barasch and Biggs, {Mary L.} and Luc Djousse and Fitzpatrick, {Annette L.} and Gottdiener, {John S.} and Ix, {Joachim H.} and Jorge Kizer and Rimm, {Eric B.} and Sicovick, {David S.} and Tracy, {Russell P.} and Mukamal, {Kenneth J.}",
year = "2014",
month = "8",
day = "1",
doi = "10.1161/CIRCEP.114.001610",
language = "English (US)",
volume = "7",
pages = "583--589",
journal = "Circulation: Arrhythmia and Electrophysiology",
issn = "1941-3149",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Fibrosis-related biomarkers and incident cardiovascular disease in older adults the cardiovascular health study

AU - Agarwal, Isha

AU - Glazer, Nicole L.

AU - Barasch, Eddy

AU - Biggs, Mary L.

AU - Djousse, Luc

AU - Fitzpatrick, Annette L.

AU - Gottdiener, John S.

AU - Ix, Joachim H.

AU - Kizer, Jorge

AU - Rimm, Eric B.

AU - Sicovick, David S.

AU - Tracy, Russell P.

AU - Mukamal, Kenneth J.

PY - 2014/8/1

Y1 - 2014/8/1

N2 - 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.

AB - 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.

KW - Cardiovascular diseases

KW - Collagen

KW - Epidemiology

KW - Heart failure

UR - http://www.scopus.com/inward/record.url?scp=84907901497&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907901497&partnerID=8YFLogxK

U2 - 10.1161/CIRCEP.114.001610

DO - 10.1161/CIRCEP.114.001610

M3 - Article

VL - 7

SP - 583

EP - 589

JO - Circulation: Arrhythmia and Electrophysiology

JF - Circulation: Arrhythmia and Electrophysiology

SN - 1941-3149

IS - 4

ER -