부산대학교 도서관

Background: Fibrotic changes in the heart and vasculature have been implicated in a diverse range of cardiovascular disease (CVD). However, limited epidemiological data exists to support such associations. Methods: We determined prospective associations of two complementary biomarkers of fibrosis, transforming growth factor- β (TGF-β, n=1,371) and procollagen type III N-terminal propeptide (PIIINP, n=2,568), with congestive heart failure (CHF), myocardial infarction (MI), and stroke among community-living older adults in the Cardiovascular Health Study over 14 years of follow-up. Due to potentially pleiotropic effects of TGF-β on inflammation and fibrosis, we investigated effect modification by C-reactive protein (CRP) in secondary analyses. Results: In age, sex, race, and site-adjusted models, higher PIIINP was associated with risk of total CVD, CHF, and stroke, as was the combined measure of TGF-β and PIIINP (sum of z-scores). Most of these associations remained statistically significant in fully-adjusted models (Table). TGF-β was not associated with CVD in the full cohort, but associations with total CVD, CHF, and stroke were statistically significant among individuals with CRP above the median (2.3 mg/L) (Pinteraction= 0.05). Associations involving PIIINP were also statistically significant and stronger among individuals with higher CRP. In the high CRP stratum, HRs for total CVD were 1.15 (CI: 1.02, 1.30) per SD TGF-β, 1.14 (CI: 1.04, 1.25) per SD PIIINP, and 1.21 (CI: 1.06, 1.38) per SD of the combined measure. In the low CRP stratum, HRs were 0.96 (CI: 0.82, 1.12) per SD of TGF-β, 1.02 (CI: 0.92, 1.12) per SD PIIINP, and 1.04 (CI: 0.90, 1.20) per SD of the combined measure. Conclusion: Our findings provide further evidence that circulating biomarkers of fibrosis, measured late in life, are associated with CVD. Research on whether TGF-β has a stronger pro-fibrotic effect in the setting of increased inflammation is warranted. [ABSTRACT FROM AUTHOR]