Elevation of plasma cell-free hemoglobin in pulmonary arterial hypertension.

Brittain EL, Janz DR, Austin ED, Bastarache JA, Wheeler LA, Ware LB, Hemnes AR
Chest. 2014 146 (6): 1478-1485

PMID: 24945582 · PMCID: PMC4251612 · DOI:10.1378/chest.14-0809

BACKGROUND - Cell-free hemoglobin (CFH) is a potent nitric oxide scavenger associated with poor outcomes in several diseases. Pulmonary arterial hypertension (PAH) is characterized by reduced nitric oxide availability. We hypothesized that CFH would be elevated in PAH and would associate with hemodynamics and clinical outcomes.

METHODS - We measured CFH in 200 consecutively evaluated patients with PAH, 16 unaffected bone morphogenetic receptor protein type 2 (BMPR2) mutation carriers, 19 healthy subjects, and 29 patients with pulmonary venous hypertension (PVH). CFH values were tested for association with hemodynamics, time to hospitalization, and death.

RESULTS - CFH was elevated in patients with PAH and BMPR2 carriers compared with healthy subjects and patients with PVH (P ≤ .01 all comparisons). There were no differences in CFH across PAH subtypes. CFH modestly correlated with mean pulmonary artery pressure (ρ = 0.16, P = .03) and pulmonary vascular resistance (ρ = 0.21, P = .01) and inversely with cardiac index (ρ = -0.18, P = .02) in patients with PAH. CFH was not associated with hemodynamic response to nitric oxide or death. Patients with the highest CFH levels had increased risk of PAH-related hospitalization when adjusted for age, sex, and PAH cause (hazard ratio, 1.69; 95% CI ,1.08-2.66; P = .02).

CONCLUSIONS - CFH is elevated in patients with PAH and BMPR2 carriers compared with healthy subjects and patients with PVH. Elevated CFH levels are independently associated with an increased risk of hospitalization. Further study is required to understand the mechanism of CFH elevation and the potential pathologic contribution of CFH in PAH.

MeSH Terms (21)

Adult Aged Biomarkers Bone Morphogenetic Protein Receptors, Type II Case-Control Studies Female Hemodynamics Hemoglobins Humans Hypertension, Pulmonary Kaplan-Meier Estimate Male Middle Aged Plasma Cells Prognosis Proportional Hazards Models Retrospective Studies Sensitivity and Specificity Severity of Illness Index Statistics, Nonparametric Vascular Resistance

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