Plasma proteoglycan prolargin in diagnosis and differentiation of pulmonary arterial hypertension

Research output: Contribution to journalArticle

Abstract

Aims: Right ventricular dysfunction may arise because of pulmonary arterial hypertension (PAH). Development of new diagnostic methods able to identify PAH and allow for earlier treatment initiation, before the development of vascular remodelling and manifest right heart failure (HF), could potentially improve prognosis. Proteoglycans and inflammatory proteins are involved in vascular remodelling. We aimed to investigate their potential as biomarkers to differentiate PAH in a dyspnoeic population. Methods and results: Plasma from 152 patients with PAH (n = 48), chronic thrombo-embolic pulmonary hypertension (n = 20), pulmonary hypertension due to HF with reduced (n = 36) or preserved (n = 33) ejection fraction, and HF without pulmonary hypertension (n = 15) and 20 healthy controls were analysed with proximity extension assays. Haemodynamics were assessed in the patients with right heart catheterization. Plasma prolargin levels in PAH were lower compared with all the other studied disease groups (P < 0.001) but higher than the controls' levels (P = 0.003). Receiver operating characteristic curve of prolargin as a PAH-differentiating marker in a pooled population, encompassing all the other studied disease groups, had a sensitivity of 74% and a specificity of 83.3% (area under the curve = 0.84, P < 0.001). Prolargin correlated with the mean right atrial pressure (rs = 0.65, P < 0.001), N-terminal pro-brain natriuretic peptide (rs = 0.64, P < 0.001), cardiac index (rs = −0.31, P = 0.029), stroke volume index (rs = −0.41, P = 0.004), right ventricular stroke work index (rs = −0.31, P = 0.032), six-minute walking distance (rs = −0.41, P = 0.005), and mixed venous blood oxygen saturation (rs = −0.42, P = 0.003). Conclusions: Plasma prolargin levels differentiate PAH patients from controls and the other investigated dyspnoea groups including HF. Its potential in PAH differentiation may be enhanced by inclusion in a multi-marker panel. Larger studies are needed to evaluate its discriminative ability of PAH in relation to other dyspnoea aetiologies and its potential role in PAH risk stratification and pathobiology.

Details

Authors
Organisations
External organisations
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cardiac and Cardiovascular Systems

Keywords

  • Differentiation, Plasma biomarkers, Prolargin, Proteoglycans, Pulmonary hypertension
Original languageEnglish
Pages (from-to)1230-1243
JournalESC Heart Failure
Volume8
Issue number2
Early online date2021 Jan 5
Publication statusPublished - 2021
Publication categoryResearch
Peer-reviewedYes