Inflammation and obesity correlate in pulmonary hypertension but associate with diverging outcomes

Résumé fourni par la source

Background: 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. Methods: Time-series clustering of longitudinal CRP levels was employed. Clinical differences between clusters were validated in three independent UK/International cohorts (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). Multi-omics were interrogated from associated previously published arrays. Results: Patients segregated into two stable CRP clusters, with strong associations with body mass index (BMI). Increased CRP and BMI associated with worse exercise capacity. Inflammation associated with worse survival, more comorbidities, higher pulmonary vascular resistance (PVR), and smoking status. No relationship was observed between CRP and circulating autoantibodies, but 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 and lower PVR and did not negatively affect treatment response. Conclusions: We establish a strong relationship between CRP and BMI across all cause PH. Despite this relationship, CRP and BMI associated 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.

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