Brittain Evan L, Janz David R, Austin Eric D, Bastarache Julie A, Wheeler Lisa A, Ware Lorraine B, Hemnes Anna R
Division of Cardiovascular Medicine, Vanderbilt University Medical School, Nashville, TN.
Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical School, Nashville, TN.
Chest. 2014 Dec;146(6):1478-1485. doi: 10.1378/chest.14-0809.
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.
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.
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).
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.
无细胞血红蛋白（CFH）是一种强效的一氧化氮清除剂，与多种疾病的不良预后相关。肺动脉高压（PAH）的特征是一氧化氮可用性降低。我们推测CFH在PAH中会升高，并与血流动力学和临床结局相关。
我们测量了200例连续评估的PAH患者、16例未受影响的骨形态发生蛋白2型（BMPR2）突变携带者、19名健康受试者和29例肺静脉高压（PVH）患者的CFH。测试CFH值与血流动力学、住院时间和死亡的相关性。
与健康受试者和PVH患者相比，PAH患者和BMPR2携带者的CFH升高（所有比较P≤0.01）。PAH各亚型之间的CFH无差异。在PAH患者中，CFH与平均肺动脉压（ρ = 0.16，P = 0.03）和肺血管阻力（ρ = 0.21，P = 0.01）呈适度相关，与心脏指数呈负相关（ρ = -0.18，P = 0.02）。CFH与对一氧化氮的血流动力学反应或死亡无关。在调整年龄、性别和PAH病因后，CFH水平最高的患者发生PAH相关住院的风险增加（风险比，1.69；95%CI，1.08 - 2.66；P = 0.02）。
与健康受试者和PVH患者相比，PAH患者和BMPR2携带者的CFH升高。CFH水平升高与住院风险增加独立相关。需要进一步研究以了解CFH升高的机制以及CFH在PAH中的潜在病理作用。
