title: Serum endostatin and risk of mortality in the elderly: findings from 2 community-based cohorts.
abstract: OBJECTIVE
  Experimental data imply that endostatin, a proteolytically cleaved fragment of collagen XVIII, could be involved in the development of cardiovascular disease and cancer. Prospective data concerning the relation between circulating endostatin and mortality are lacking. Accordingly, we aimed to study associations between circulating endostatin and mortality risk.
  
  
  RESULTS
  Serum endostatin was analyzed in 2 community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n=931; mean age, 70 years; median follow-up, 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=748; mean age, 77 years; median follow-up, 9.7 years). During follow-up, 90 participants died in PIVUS (1.28/100 person-years at risk), and 417 participants died in ULSAM (6.7/100 person-years at risk). In multivariable Cox regression models adjusted for age and established cardiovascular risk factors, 1 SD higher ln(serum endostatin level) was associated with a hazard ratio of mortality of 1.39 and 95% confidence interval, 1.26 to 1.53, on average in both cohorts. In the ULSAM cohort, serum endostatin was also associated with cardiovascular mortality (177 deaths; hazard ratio per SD of ln[endostatin] 1.45, 95% confidence interval [1.25-1.71]) and cancer mortality (115 deaths; hazard ratio per SD of ln[endostatin] 1.35, 95% confidence interval [1.10-1.66]).
  
  
  CONCLUSIONS
  High serum endostatin was associated with increased mortality risk in 2 independent community-based cohorts of the elderly. Our observational data support the importance of extracellular matrix remodeling in the underlying pathophysiology of cardiovascular disease and cancer.
authors.affiliation: From the Department of Public Health and Caring Sciences/Section of Geriatrics (J.Ä.), Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden (E.I., J.Ä.); Department of Medical Sciences, Uppsala University, Uppsala, Sweden (A.L., J.S., L.L.); School of Health and Social Studies, Dalarna University, Falun, Sweden (J.Ä.); and Department of Surgery, Umea University, Umea, Sweden (T.R.).
authors.forename: Johan
authors.initials: J
authors.lastname: Ärnlöv
authors.forename: Toralph
authors.initials: T
authors.lastname: Ruge
authors.forename: Erik
authors.initials: E
authors.lastname: Ingelsson
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.forename: Johan
authors.initials: J
authors.lastname: Sundström
authors.forename: Lars
authors.initials: L
authors.lastname: Lind
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000401:mortality*; D043169:Endostatins / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009369:Neoplasms / Q000378:metabolism* / Q000401:mortality*; D016016:Proportional Hazards Models; D012111:Residence Characteristics; D012307:Risk Factors
chemical_list: D043169:Endostatins
keywords: cardiovascular diseases; endostatin; epidemiology; extracelluler matrix proteins; mortality; neoplasms