02905nas a2200505 4500008004100000022001400041245011300055210006900168260001600237300001100253490000800264520146700272653000901739653002201748653001501770653001901785653001101804653001301815653002201828653001101850653002501861653000901886653002601895653002201921653001601943653003201959653002401991653001702015653003602032100001802068700002202086700001802108700001902126700001802145700002802163700002402191700001902215700002002234700001802254700002402272700002202296700002102318700002402339856003602363 2014 eng d a1476-625600aFibrosis-related biomarkers and risk of total and cause-specific mortality: the cardiovascular health study.0 aFibrosisrelated biomarkers and risk of total and causespecific m c2014 Jun 01 a1331-90 v1793 a
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.
10aAged10aAged, 80 and over10aBiomarkers10aCause of Death10aFemale10aFibrosis10aFollow-Up Studies10aHumans10aLikelihood Functions10aMale10aMultivariate Analysis10aPeptide Fragments10aProcollagen10aProportional Hazards Models10aProspective Studies10aRisk Factors10aTransforming Growth Factor beta1 aAgarwal, Isha1 aGlazer, Nicole, L1 aBarasch, Eddy1 aBiggs, Mary, L1 aDjoussé, Luc1 aFitzpatrick, Annette, L1 aGottdiener, John, S1 aIx, Joachim, H1 aKizer, Jorge, R1 aRimm, Eric, B1 aSiscovick, David, S1 aTracy, Russell, P1 aZieman, Susan, J1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/6336