title: Evaluation of circulating proteins and hemodynamics towards predicting mortality in children with pulmonary arterial hypertension.
abstract: BACKGROUND
  Although many predictors have been evaluated, a set of strong independent prognostic mortality indicators has not been established in children with pediatric pulmonary arterial hypertension (PAH). The aim of this study was to identify a combination of clinical and molecular predictors of survival in PAH.
  
  
  METHODS
  This single-center, retrospective cohort study was performed from children with PAH between 2001 and 2008 at Children's Hospital Colorado. Blood samples from 83 patients (median age of 8.3 years-old) were obtained. We retrospectively analyzed 46 variables, which included 27 circulating proteins, 7 demographic variables and 12 hemodynamic and echocardiographic variables for establishing the best predictors of mortality. A data mining approach was utilized to evaluate predictor variables and to uncover complex data structures while performing variable selection in high dimensional problems.
  
  
  RESULTS
  Thirteen children (16%) died during follow-up (median; 3.1 years) and survival rates from time of sample collection at 1 year, 3 years and 5 years were 95%, 85% and 79%, respectively. A subset of potentially informative predictors were identified, the top four are listed here in order of importance: Tissue inhibitors of metalloproteinases-1 (TIMP-1), apolipoprotein-AI, RV/LV diastolic dimension ratio and age at diagnosis. In univariate analysis, TIMP-1 and apolipoprotein-AI had significant association with survival time (hazard ratio [95% confidence interval]: 1.25 [1.03, 1.51] and 0.70 [0.54-0.90], respectively). Patients grouped by TIMP-1 and apolipoprotein-AI values had significantly different survival risks (p<0.01).
  
  
  CONCLUSIONS
  Important predictors of mortality were identified from a large number of circulating proteins and clinical markers in this cohort. If confirmed in other populations, measurement of a subset of these predictors could aid in management of pediatric PAH by identifying patients at risk for death. These findings also further support a role for the clinical utility of measuring circulating proteins.
authors.affiliation: Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Brandie D
authors.initials: BD
authors.lastname: Wagner
authors.forename: Shinichi
authors.initials: S
authors.lastname: Takatsuki
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Accurso
authors.forename: David Dunbar
authors.initials: DD
authors.lastname: Ivy
mesh_terms: D001798:Blood Proteins / Q000378:metabolism*; D002648:Child; D005260:Female; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000401:mortality* / Q000503:physiopathology; D057230:Limit of Detection; D008297:Male; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D001798:Blood Proteins