Serum apelin levels in established pulmonary arterial hypertension: A cross-sectional case-control study

Pulmonary arterial hypertension (PAH) is a progressive condition involving pulmonary vasoconstriction, vascular remodeling, abnormal angiogenesis, and right ventricular dysfunction. Apelin, an endogenous peptide acting via the APJ receptor, modulates vascular tone, enhances nitric oxide-mediated vasodilation, and counteracts the renin-angiotensin system, suggesting relevance to PAH.

To compare serum apelin levels between patients with established PAH and healthy controls and to examine their relationship with cross-sectional measures of disease severity.

In this prospective cross-sectional study, 40 patients with established Group 1 PAH receiving PAH-specific therapy and 40 age- and sex-matched healthy controls were enrolled. All participants underwent echocardiographic evaluation, a six-minute walk test, and serum apelin measurement. PAH patients were additionally classified using the 2022 ESC/ERS four-strata risk model and WHO functional class.

Serum apelin levels were significantly higher in PAH patients than in controls (1006.20 ± 312.99 pg/mL vs. 812.46 ± 245.80 pg/mL; p = 0.003). Apelin levels did not differ significantly across PAH etiologies (p = 0.16), ESC/ERS risk strata (p = 0.84), or WHO functional classes (p = 0.06). In multivariable logistic regression, apelin remained independently associated with PAH status (OR 1.345 per 100 pg/mL; 95% CI 1.084-1.669; p = 0.007).

Serum apelin levels were higher in patients with established PAH than in healthy controls and were independently associated with PAH status, whereas no significant association with the evaluated cross-sectional severity measures was demonstrated. Any potential diagnostic role of apelin requires validation in newly diagnosed, treatment-naïve patients and clinically relevant comparator groups.