Nakamura Hiroyuki, Kato Masaru, Nakaya Toshitaka, Kono Michihiro, Tanimura Shun, Sato Takahiro, Fujieda Yuichiro, Oku Kenji, Ohira Hiroshi, Bohgaki Toshiyuki, Yasuda Shinsuke, Tsujino Ichizo, Nishimura Masaharu, Atsumi Tatsuya
Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University First Department of Medicine, Hokkaido University Hospital, Sapporo, Japan.
Medicine (Baltimore). 2017 Oct;96(43):e8349. doi: 10.1097/MD.0000000000008349.
We investigated the serum haptoglobin levels in patients with pulmonary arterial hypertension (PAH) based on the hypothesis that haptoglobin levels would reflect subclinical hemolysis due to microangiopathy in pulmonary arterioles.This cross-sectional study included 3 groups of patients attending Hokkaido University Hospital: PAH, chronic thromboembolic pulmonary hypertension (CTEPH), and connective tissue diseases (CTD) without PAH (CTD-non-PAH) group. Serum haptoglobin levels were measured by standardized turbidimetric immunoassay in all patients. Demographic data, laboratory results, right heart catheter, and echocardiographic findings were extracted from the medical records. Decreased haptoglobin levels were defined as below 19 mg/dL based on the 95th percentile of healthy controls.Thirty-five patients in PAH group including 11 with idiopathic PAH (IPAH) and 24 with CTD-associated PAH (CTD-PAH), 27 in CTEPH group, and 32 in CTD-non-PAH group were analyzed. Serum haptoglobin levels in PAH group (median 66 mg/dL) were significantly lower than those in CTEPH group (median 94 mg/dL, P = .03) and CTD-non-PAH group (median 79 mg/dL, P = .03). The prevalence of decreased haptoglobin levels was 26% in PAH group, 15% in CTEPH group, and 6% in CTD-non-PAH group. Serum haptoglobin levels had a significant negative correlation (r = -0.66, P < .001) with mean pulmonary artery pressure in PAH group, particularly in CTD-PAH subgroup (r = -0.74, P < .001), but no correlation in IPAH subgroup (r = -0.52, P = .13) and in CTEPH group (r = -0.17, P = .41). Follow-up cases of CTD-PAH showed lowering pulmonary artery pressure led to normalizing serum haptoglobin levels.Serum haptoglobin levels decreased in PAH patients and inversely correlated with pulmonary artery pressure in CTD-PAH patients, suggesting their potential as a surrogate marker for CTD-PAH.
我们基于触珠蛋白水平会反映因肺小动脉微血管病导致的亚临床溶血这一假设，对肺动脉高压（PAH）患者的血清触珠蛋白水平进行了研究。这项横断面研究纳入了三组在北海道大学医院就诊的患者：PAH组、慢性血栓栓塞性肺动脉高压（CTEPH）组以及无PAH的结缔组织病（CTD）组（CTD-非PAH组）。对所有患者均采用标准化比浊免疫分析法测定血清触珠蛋白水平。从病历中提取人口统计学数据、实验室检查结果、右心导管检查及超声心动图检查结果。根据健康对照者的第95百分位数，将触珠蛋白水平降低定义为低于19mg/dL。分析了PAH组的35例患者，其中包括11例特发性PAH（IPAH）患者和24例CTD相关性PAH（CTD-PAH）患者，CTEPH组的27例患者，以及CTD-非PAH组的32例患者。PAH组的血清触珠蛋白水平（中位数66mg/dL）显著低于CTEPH组（中位数94mg/dL，P = 0.03）和CTD-非PAH组（中位数79mg/dL，P = 0.03）。PAH组触珠蛋白水平降低的患病率为26%，CTEPH组为15%，CTD-非PAH组为6%。在PAH组中，血清触珠蛋白水平与平均肺动脉压呈显著负相关（r = -0.66，P < 0.001）；在CTD-PAH亚组中尤其如此（r = -0.74，P < 0.001），但在IPAH亚组（r = -0.5）和CTEPH组中无相关性（r = -0.17，P = 0.41）。CTD-PAH的随访病例显示，肺动脉压降低会使血清触珠蛋白水平恢复正常。PAH患者的血清触珠蛋白水平降低，且在CTD-PAH患者中与肺动脉压呈负相关，提示其有可能作为CTD-PAH的替代标志物。
