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Abstract：
Various erythropoietic abnormalities are highly prevalent among patients with pulmonary arterial hypertension (PAH) and associated with worse disease severity. Given the poorly understood yet important roles of dysregulated erythropoiesis and iron metabolism in PAH, we sought to further characterize the hematologic and iron profiles in PAH and their relationship to PAH severity. We recruited 67 patients with PAH and 13 healthy controls. Hemodynamics attained within 1 year of blood sample collection were available for 36 patients. Multiple hematologic, iron, and inflammatory parameters were evaluated for their association with hemodynamics. The subset with hemodynamic data consisted of 29 females (81%). The most common etiologies were idiopathic PAH (47%) and connective tissue disease-related PAH (33%). 19 (53%) had functional class 3 or 4 symptomatology, and 12 (33%) were on triple pulmonary vasodilator therapy. Immature reticulocyte fraction (IRF) had significant positive correlations with mean pulmonary artery (PA) pressure (mPAP) (0.59, p < 0.001), pulmonary vascular resistance (0.52, p = 0.001), and right atrial pressure (0.46, p = 0.005), and significant negative correlations with cardiac index (-0.43, p = 0.009), PA compliance (PAC) (-0.60, p < 0.001), stroke volume index (SVI) (-0.57, p < 0.001), and mixed venous oxygen saturation (-0.51, p = 0.003). IRF correlated with markers of iron deficiency (ID) and erythropoiesis. On multivariable linear regression, IRF was associated with elevated mPAP and reduced SVI and PAC independent of EPO levels, transferrin saturation, and soluble transferrin receptor levels. We identified IRF as a novel and potent biomarker of PAH hemodynamic severity, possibly related to its associations with erythropoiesis, ID, and tissue hypoxia.
摘要：
各种红细胞生成异常在肺动脉高压（PAH）患者中非常普遍，并且与疾病严重程度更差有关。鉴于人们对红细胞生成失调和铁代谢在PAH中的重要作用知之甚少，我们试图进一步描述PAH的血液学和铁特征及其与PAH严重程度的关系.我们招募了67例PAH患者和13例健康对照。36名患者在血液样本收集的1年内获得了血液动力学。多发性血液学，铁,评估炎症参数与血流动力学的相关性。具有血液动力学数据的子集包括29名女性(81%)。最常见的病因是特发性PAH（47％）和结缔组织疾病相关的PAH（33％）。19（53%）有功能3级或4级症状，12例(33%)接受三联肺血管扩张剂治疗。未成熟网织红细胞分数(IRF)与平均肺动脉压(mPAP)呈显著正相关(0.59,p<0.001),肺血管阻力（0.52，p=0.001），和右心房压力（0.46，p=0.005），与心脏指数呈显著负相关(-0.43，p=0.009)，PA依从性（PAC）（-0.60，p<0.001），每搏量指数（SVI）（-0.57，p<0.001），和混合静脉血氧饱和度（-0.51，p=0.003）。IRF与铁缺乏（ID）和红细胞生成的标志物相关。关于多元线性回归，IRF与mPAP升高和SVI和PAC降低相关，与EPO水平无关。转铁蛋白饱和度，和可溶性转铁蛋白受体水平。我们将IRF确定为PAH血流动力学严重程度的新型有效生物标志物，可能与红细胞生成有关，ID,和组织缺氧。
