Usefulness of Circulating Amino Acid Profile and Fischer Ratio to Predict Severity of Pulmonary Hypertension

Abstract

Plasma amino acid concentrations (aminogram) show distinct patterns under various pathologic conditions. However, the plasma aminogram pattern in patients with pulmonary hypertension (PH) has not been elucidated. We sought to examine whether an aminogram could be predictive of clinical severity in patients with PH. We attained fasting plasma aminograms for 140 patients with PH and then compared the patient plasma amino acid levels with those of age- and gender-matched healthy control subjects. Aminograms revealed that the plasma concentrations of many amino acids were significantly different between patients with PH and healthy control subjects. We focused on the Fischer ratio (branched-chain amino acids/aromatic amino acids) as an integrated parameter. In all enrolled patients, Fischer ratio was negatively correlated with New York Heart Association functional class (ρ = -0.37, p <0.001), plasma B-type natriuretic peptide (ρ = -0.35, p <0.001), and pulmonary vascular resistance (ρ = -0.27, p = 0.002) and positively correlated with venous oxygen saturation (ρ = 0.27, p = 0.002) and 6-minute walk distance (ρ = 0.23, p = 0.016). Time course changes in Fischer ratio and in cardiac output were significantly correlated (ρ = 0.39, p = 0.024). The aminogram is changed in patients with PH, and in these patients, Fischer ratio decreases in proportion to the clinical severity of PH.