{
  "abstract": "Rationale and 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 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.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=2 mmHg) 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.",
  "authors": [
    {
      "affiliations": [
        "University of Cambridge, Cambridge, UK"
      ],
      "name": "EMDDDe Bie"
    },
    {
      "affiliations": [
        "Mount Sinai Icahn School of Medicine, New York, USA"
      ],
      "name": "P Correa-Jaque"
    },
    {
      "affiliations": [
        "University of Cambridge, Cambridge, UK"
      ],
      "name": "R Jones"
    },
    {
      "affiliations": [
        "Amsterdam University Medical Centre, Amsterdam, Netherlands"
      ],
      "name": "HJ Bogaard"
    },
    {
      "affiliations": [
        "University of Cambridge, Cambridge, UK"
      ],
      "name": "J Chan"
    },
    {
      "affiliations": [
        "Golden Jubilee National Hospital, Glasgow, UK"
      ],
      "name": "C Church"
    },
    {
      "affiliations": [
        "Royal Free Hospital, London, UK"
      ],
      "name": "JG Coghlan"
    },
    {
      "affiliations": [
        "University of Sheffield, Sheffield, UK"
      ],
      "name": "A Gaur"
    },
    {
      "affiliations": [
        "Fondazione IRCCS Policlinico San Matteo, Pavia, Italy"
      ],
      "name": "S Ghio"
    },
    {
      "affiliations": [
        "University of Giessen and Marburg Lung Center, Giessen, Germany"
      ],
      "name": "HA Ghofrani"
    },
    {
      "affiliations": [
        "University of Sheffield, Sheffield, UK"
      ],
      "name": "ZM Goh"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College, London, UK"
      ],
      "name": "LS Howard"
    },
    {
      "affiliations": [
        "Université Paris-Saclay, Le Kremlin-Bicêtre, Paris, France"
      ],
      "name": "M Humbert"
    },
    {
      "affiliations": [
        "Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria"
      ],
      "name": "G Kovacs"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College, London, UK"
      ],
      "name": "A Lawrie"
    },
    {
      "affiliations": [
        "Freeman Hospital, Newcastle upon Tyne, UK"
      ],
      "name": "J Lordan"
    },
    {
      "affiliations": [
        "University of Cambridge, Cambridge, UK"
      ],
      "name": "WY Lin"
    },
    {
      "affiliations": [
        "University of Sheffield, Sheffield, UK"
      ],
      "name": "D Neelam-Naganathan"
    },
    {
      "affiliations": [
        "University of Cambridge, Cambridge, UK"
      ],
      "name": "J Newman"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College, London, UK"
      ],
      "name": "CJ Rhodes"
    },
    {
      "affiliations": [
        "Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK"
      ],
      "name": "K Sheares"
    },
    {
      "affiliations": [
        "Université Paris-Saclay, Le Kremlin-Bicêtre, Paris, France"
      ],
      "name": "O Sitbon"
    },
    {
      "affiliations": [
        "University of Cambridge, Cambridge, UK"
      ],
      "name": "TW Willis"
    },
    {
      "affiliations": [
        "National Heart and Lung Institute, Imperial College, London, UK"
      ],
      "name": "SJ Wort"
    },
    {
      "affiliations": [
        "University of Cambridge, Cambridge, UK"
      ],
      "name": "S Gräf"
    },
    {
      "affiliations": [
        "University of Sheffield, Sheffield, UK"
      ],
      "name": "DG Kiely"
    },
    {
      "affiliations": [
        "Mount Sinai Icahn School of Medicine, New York, USA"
      ],
      "name": "RL Benza"
    },
    {
      "affiliations": [
        "University of Sheffield, Sheffield, UK"
      ],
      "name": "AMK Rothman"
    },
    {
      "affiliations": [
        "University of Cambridge, Cambridge, UK"
      ],
      "name": "C Wallace"
    },
    {
      "affiliations": [
        "University of Cambridge, Cambridge, UK"
      ],
      "name": "MR Toshner"
    }
  ],
  "title": "S146 Inflammation and obesity correlate in pulmonary hypertension but associate with diverging outcomes",
  "uid": "f308314a-ea49-5f6d-93b6-4a11753c048c"
}