Inflammation and obesity correlate in pulmonary hypertension but associate with diverging outcomes
File(s)
Accepted version
Supporting information
Author(s)
Type
Journal Article
Abstract
Rationale & Objectives: Inflammation is associated with all types of Pulmonary Hypertension (PH) both as a known cause and/or a putative confounder. The most common marker of inflammation, C-reactive protein (CRP), has not been widely studied in PH. This study set out to clarify if CRP informed clinical endotyping and outcomes. Methods & Measurements: Time-series clustering of longitudinal CRP levels was employed. Clinical differences between clusters were validated in three independent UK/international cohorts using clinical cut off values (n=10,301; UK-cohort, ASPIRE and FDA cohort). Associations were analysed with functional and mortality outcomes by linear and Cox regression models including all-causes of PH (groups 1-5). To add mechanistic insight, multi-omics were interrogated from associated previously published arrays. Main Results: Patients segregated into two stable CRP clusters (median CRP 2 versus 6.5 mg/l), with the high cluster exhibiting significantly higher BMI (difference between medians DBM=5.4 kg/m2), higher RAP (DBM=2mmHg) and reduced 6-minute walk distance (6MWD (DBM=55m)). Inflammation was associated with worse survival, comorbidities, higher pulmonary vascular resistance (PVR), and smoking status. CRP and BMI were associated with differing inflammatory profiles in proteomic and transcriptomic analyses. Despite the relationship with CRP, higher BMI associated with improved survival, lower PVR and did not negatively affect 6MWD treatment-related functional responses. Conclusions: We establish a relationship between CRP and BMI across all-cause PH, though CRP and BMI associate with diverging clinical outcomes. Inflammation and obesity are relevant phenotypes for consideration in clinical trial design. Understanding their impacts on outcomes is important for clinical practice.
Date Issued
2026-01-01
Date Acceptance
2025-08-06
Citation
American Journal of Respiratory and Critical Care Medicine, 2026, 212 (1), pp.117-128
ISSN
1073-449X
Publisher
American Thoracic Society
Start Page
117
End Page
128
Journal / Book Title
American Journal of Respiratory and Critical Care Medicine
Volume
212
Issue
1
Copyright Statement
© American Thoracic Society, All Rights Reserved. This is the author’s accepted manuscript made available under a CC-BY licence in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy)
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40788756
Subjects
Body mass index
C-Reactive protein
Inflammation
Obesity
Pulmonary hypertension
Publication Status
Published
Coverage Spatial
United States
Article Number
rccm.202412-2393OC
Date Publish Online
2025-08-11