Do single or sequential measurements of leptin and adiponectin in plasma have prognostic value in pulmonary arterial hypertension?

Leptin (a neuroendocrine peptide that enhances metabolism and acts on the hypothalamus to suppress appetite) and adiponectin (a protein that has insulin-sensitizing, anti-inflammatory, and antiproliferative properties) are involved in the pathobiology of pulmonary arterial hypertension (PAH). We hypothesized that plasma leptin and adiponectin as well as the leptin/adiponectin ratio are abnormal in PAH patients and their levels track with disease severity and functional changes during follow-up. We tested this hypothesis in a cohort of patients included in the 16-week, international, multicenter, double-blind, placebo-controlled FREEDOM-C2 study. Blood was collected at baseline and week 16 in 178 out of 310 randomized patients with PAH. Baseline plasma leptin and adiponectin concentrations were 25 ± 31 ng/mL and 7.8 ± 6.1 ug/mL, respectively. Leptin, adiponectin, and leptin/adiponectin (mean ± SD) changes at 16 week were of small magnitude. Leptin at baseline was significantly associated with older age, higher BMI, higher Borg dyspnea index, and lower NT-pro BNP. Women had higher levels of leptin than men (30.5 ± 33.2 versus 7.2 ± 6.4 ng/mL), even when adjusting for background therapy and etiology (linear regression: β = 21.8, P < 0.001). Adiponectin was negatively associated with BMI and positively associated with NT-pro BNP. Changes in leptin, adiponectin, and leptin/adiponectin ratio adjusted for weight at 16 weeks did not predict functional class, distance walk in 6 min or survival at one, two, three, or four years. Plasma leptin and adiponectin at baseline and their change at 16-week do not appear to significantly impact prognosis in PAH.