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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Wang, RS; Huang, S; Waldo, SW; Hess, E; Gokhale, M; Johnson, SW; Zeder, K; Choudhary, G; Leopold, JA; Oldham, WM; Kovacs, G; Freiberg, MS; Tedford, RJ; Maron, BA; Brittain, EL.
Elevated Pulmonary Arterial Compliance Is Associated with Survival in Pulmonary Hypertension: Results from a Novel Network Medicine Analysis
AM J RESP CRIT CARE. 2023; 208(3): 312-321.
Doi: 10.1164/rccm.202211-2097OC
[OPEN ACCESS]
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Kovacs Gabor
- Zeder Katarina Eleonora
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- Abstract:
- Rationale: Predictors of adverse outcome in pulmonary hypertension (PH) are well established; however, data that inform survival are lacking. Objectives: We aim to identify clinical markers and therapeutic targets that inform the survival in PH. Methods: We included data from patients with elevated mean pulmonary artery pressure (mPAP) diagnosed by right heart catheterization in the U.S. Veterans Affairs system (October 1, 2006-September 30, 2018). Network medicine framework was used to subgroup patients when considering an N of 79 variables per patient. The results informed outcome analyses in the discovery cohort and a sex-balanced validation right heart catheterization cohort from Vanderbilt University (September 24, 1998-December 20, 2013). Measurements and Main Results: From an N of 4,737 complete case patients with mPAP of 19-24mmHg, there were 21 distinct subgroups (network modules) (all-cause mortality range = 15.9-61.2% per module). Pulmonary arterial compliance (PAC) drove patient assignment to modules characterized by increased survival. When modeled continuously in patients with mPAP >19mmHg (N= 37,744; age, 67.2 yr [range = 61.7-73.8 yr]; 96.7% male; median follow-up time, 1,236 d [range = 570-1,971 d]), the adjusted all-cause mortality hazard ratio was,1.0 beginning at PAC >3.0ml/mmHg and decreased progressively to similar to 7ml/mmHg. A protective association between PAC >3.0ml/mmHg and mortality was also observed in the validation cohort (N= 1,514; age, 60.2yr [range= 49.2-69.1 yr]; 48.0% male; median follow-up time, 2,485 d [range = 671-3,580 d]). The association was strongest in patients with precapillary PH at the time of catheterization, in whom 41% (95% confidence interval, 0.55-0.62; P, 0.001) and 49% (95% confidence interval, 0.38-0.69; P, 0.001) improvements in survival were observed for PAC >3.0 versus,3.0ml/mmHg in the discovery and validation cohorts, respectively. Conclusions: These data identify elevated PAC as an important parameter associated with survival in PH. Prospective studies are warranted that consider PAC >3.0 ml/mm Hg as a therapeutic target to achieve through proven interventions.
- Find related publications in this database (Keywords)
- hypertension
- pulmonary
- hemodynamics
- survival
- network medicine