Evaluation of circulating proteins and hemodynamics towards predicting mortality in children with pulmonary arterial hypertension.
Evaluation of circulating proteins and hemodynamics towards predicting mortality in children with pulmonary arterial hypertension.
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DOI：
10.1371/journal.pone.0080235
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ivy DD
中科院分区：
文献类型：
--
作者：
Wagner BD;Takatsuki S;Accurso FJ;Ivy DD
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. 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. 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). 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.
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影响因子：
168.9
作者：
Berger, Rolf M. F.;Beghetti, Maurice;Humpl, Tilman;Raskob, Gary E.;Ivy, D. Dunbar;Jing, Zhi-Cheng;Bonnet, Damien;Schulze-Neick, Ingram;Barst, Robyn J.
通讯作者：
Barst, Robyn J.
影响因子：
3.5
作者：
Lammers, Astrid E.;Hislop, Alison A.;Haworth, Sheila G.
通讯作者：
Haworth, Sheila G.
影响因子：
37.8
作者：
Barst, RJ;Maislin, G;Fishman, AP
通讯作者：
Fishman, AP
影响因子：
9.6
作者：
McLaughlin, VV;Presberg, KW;Ahearn, G
通讯作者：
Ahearn, G
影响因子：
9.6
作者：
Bernus, Anna;Wagner, Brandie D.;Ivy, D. Dunbar
通讯作者：
Ivy, D. Dunbar