# Network medicine, risk stratification, and pulmonary hypertension

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $123,470

## Abstract

Project Summary/Abstract
Pulmonary hypertension (PH) is an independent risk factor for adverse outcome across the spectrum of medical
diseases. However, there is wide variability in clinical event rates within PH populations: the estimated 5-year
mortality rate following PH diagnosis is ~48% in right heart catheterization (RHC) registries, whereas normal
lifespan is reported for a sizeable subgroup of patients with severe PH. Understanding the clinical profiles
corresponding to PH risk and resilience has important implications on prognosis and individualized treatment
planning. Traditional methods for classifying and prognosticating patients use reductionist methods, such as
linear regression-based models, which provide important information on individual risk predictors. However, such
probabilistic methods do not consider interdependent relationships between variables for classifying patients,
and, thus, provide limited knowledge on key clinical parameters that integrate to determine phenotypes. In this
proposal, we present novel preliminary data to illustrate the utility of network (Bayesian) methods for enhancing
classification and risk stratification of patients. Specifically, we developed a correlation network based on data
from a large cohort of patients with unexplained exercise intolerance undergoing cardiopulmonary exercise
testing. Our findings focused on a novel collection of 10 interrelated exercise variables that identified 4 patient
groups, which were independent of traditional exercise diagnoses and associated with distinctly different clinical
profiles and clinical event rates. An overarching goal of this project is to apply this network methodology to PH.
 The Veterans Affairs Clinical Assessment, Reporting and Tracking (VA-CART) program includes RHC,
clinical, and outcome data from a national patient cohort. We recently analyzed data from RHC patients in VA-
CART (2007-2012; N=21,727), and observed that the prevalence of PH was 57%. The adjusted hazard ratio for
PH was 2.16 (95% confidence interval, 1.96-2.38, P<0.001) compared to non-PH patients. These data affirm the
importance of PH on survival; however, the factors influencing outcome within PH patients remain unknown.
Thus, the central hypothesis of this proposal is: Analyzing the VA-CART database using network methods
will discover novel PH subgroups defined by a unique collection of variables, distinct clinical profiles,
and significant outcome differences. The study aims are (1) develop a correlation network using RHC and
other data to discover novel PH subgroups defined by unique clinical and outcome profiles, and (2) use
Betweeness centrality analyses to determine clinical variables that differentiate survivors vs. non-survivors (e.g.,
resilience vs. risk, respectively) in PH. Our network findings from VA-CART will also be validated in a second,
gender-balanced and outcome-linked RHC database (Vanderbilt University). Collectively, these studies leverage
network methods...

## Key facts

- **NIH application ID:** 9851952
- **Project number:** 5R21HL145420-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Bradley Maron
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $123,470
- **Award type:** 5
- **Project period:** 2019-02-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851952

## Citation

> US National Institutes of Health, RePORTER application 9851952, Network medicine, risk stratification, and pulmonary hypertension (5R21HL145420-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9851952. Licensed CC0.

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