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2014 ; 179
(11
): 1331-9
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Fibrosis-related biomarkers and risk of total and cause-specific mortality: the
cardiovascular health study
#MMPMID24771724
Agarwal I
; Glazer NL
; Barasch E
; Biggs ML
; Djoussé L
; Fitzpatrick AL
; Gottdiener JS
; Ix JH
; Kizer JR
; Rimm EB
; Siscovick DS
; Tracy RP
; Zieman SJ
; Mukamal KJ
Am J Epidemiol
2014[Jun]; 179
(11
): 1331-9
PMID24771724
show ga
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-? (TGF-?) 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-? and PIIINP levels in plasma samples
collected in 1996 and ascertained the number of deaths through 2010. Both TGF-?
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-? 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-? and 1.52 (CI: 1.11, 2.10; P =
0.01) for PIIINP. Associations of TGF-? 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.