Abstract：
BACKGROUND: Hereditary angioedema (HAE) due to C1-inhibitor (C1-INH) deficiency is characterized by unpredictable recurrent episodes of swelling affecting the skin and the mucosa tissues, including gastrointestinal tract and/or oropharyngeal-laryngeal mucosae. Long-term prophylaxis (LTP) is used to prevent attacks.
OBJECTIVE: Because C1-INH plays a pivotal role in several biological pathways, we investigated the possible association of comorbidities with C1-INH deficiency and the use of LTP with attenuated androgens (AA) or tranexamic acid (TXA).
METHODS: This retrospective cohort study involved adult patients with HAE referred to Milan and Padua angioedema centers in the period 1979-2021. A qualitative comparison was performed to analyze comorbidities versus general population. The incidence of comorbidities was evaluated during LTP with AA or TXA versus patients without LTP.
RESULTS: A total of 446 patients were studied. A greater prevalence among patients was found for heart diseases (9.6% vs 4.8%), acute myocardial infarction (5.6% vs 1.4%), hepatitis C virus infection (10.5% vs 2.5%), and appendectomy (15.9% vs 4.3%). In patients taking AA, a greater incidence was found for hypertension (22.8% vs 10.8%; odds ratio [OR]: 2.02), hypercholesterolemia (19.5% vs 5.3%; OR: 3.97), diabetes mellitus (5% vs 1.4%; OR: 3.21), hepatic angioma (4.4% vs 0.7%; OR: 8.35), and focal nodular hyperplasia (2.5% vs 0.4%; OR: 6.9). No association between TXA and comorbidities was found.
CONCLUSIONS: In this large patient population with a rare disease followed for up to a 43-year period, we found a greater prevalence of comorbidities hitherto unreported in the literature and an association between comorbidities and LTP with AA.
OBJECTIVE: Because C1-INH plays a pivotal role in several biological pathways, we investigated the possible association of comorbidities with C1-INH deficiency and the use of LTP with attenuated androgens (AA) or tranexamic acid (TXA).
METHODS: This retrospective cohort study involved adult patients with HAE referred to Milan and Padua angioedema centers in the period 1979-2021. A qualitative comparison was performed to analyze comorbidities versus general population. The incidence of comorbidities was evaluated during LTP with AA or TXA versus patients without LTP.
RESULTS: A total of 446 patients were studied. A greater prevalence among patients was found for heart diseases (9.6% vs 4.8%), acute myocardial infarction (5.6% vs 1.4%), hepatitis C virus infection (10.5% vs 2.5%), and appendectomy (15.9% vs 4.3%). In patients taking AA, a greater incidence was found for hypertension (22.8% vs 10.8%; odds ratio [OR]: 2.02), hypercholesterolemia (19.5% vs 5.3%; OR: 3.97), diabetes mellitus (5% vs 1.4%; OR: 3.21), hepatic angioma (4.4% vs 0.7%; OR: 8.35), and focal nodular hyperplasia (2.5% vs 0.4%; OR: 6.9). No association between TXA and comorbidities was found.
CONCLUSIONS: In this large patient population with a rare disease followed for up to a 43-year period, we found a greater prevalence of comorbidities hitherto unreported in the literature and an association between comorbidities and LTP with AA.
摘要：
背景：由于C1抑制剂缺乏（HAE）引起的遗传性血管性水肿的特征是不可预测的复发性肿胀发作影响皮肤和粘膜组织，包括胃肠道和/或口咽喉粘膜。长期预防（LTP）用于预防发作。
目的：由于C1抑制剂（C1-INH）在几种生物学途径中起关键作用，我们调查了合并症与C1-INH缺乏以及LTP与雄激素(AA)或氨甲环酸(TXA)的使用之间的可能关联.
方法：这项回顾性队列研究涉及1979-2021年米兰和帕多瓦血管性水肿中心的成人HAE患者。进行了定性比较，以分析合并症与一般人口。在使用AA或TXA与LTP期间评估合并症的发生率。无LTP的患者。
结果：共研究了446例患者。在患者中发现更高的患病率：心脏病(9.6%vs.4.8%），急性心肌梗死（5.6%vs.1.4%），HCV感染（10.5%vs.2.5%），和阑尾切除术(15.9%vs.4.3%）。在服用AA的患者中，高血压的发病率更高(22.8%vs.10.8%；OR2.02)，高胆固醇血症（19.5%vs.5.3%；OR3.97)，糖尿病（5%vs.1.4%；OR3.21)，肝血管瘤（4.4%vs.0.7%；OR8.35），和局灶性结节增生(2.5%vs.0.4%；OR6.9）。未发现与TXA和合并症的关联。
结论：在这个患有罕见疾病的庞大患者群体中，随访长达43年，我们发现,迄今为止文献中未报道的合并症患病率更高,并且合并症和LTP与AA之间存在关联.
目的：由于C1抑制剂（C1-INH）在几种生物学途径中起关键作用，我们调查了合并症与C1-INH缺乏以及LTP与雄激素(AA)或氨甲环酸(TXA)的使用之间的可能关联.
方法：这项回顾性队列研究涉及1979-2021年米兰和帕多瓦血管性水肿中心的成人HAE患者。进行了定性比较，以分析合并症与一般人口。在使用AA或TXA与LTP期间评估合并症的发生率。无LTP的患者。
结果：共研究了446例患者。在患者中发现更高的患病率：心脏病(9.6%vs.4.8%），急性心肌梗死（5.6%vs.1.4%），HCV感染（10.5%vs.2.5%），和阑尾切除术(15.9%vs.4.3%）。在服用AA的患者中，高血压的发病率更高(22.8%vs.10.8%；OR2.02)，高胆固醇血症（19.5%vs.5.3%；OR3.97)，糖尿病（5%vs.1.4%；OR3.21)，肝血管瘤（4.4%vs.0.7%；OR8.35），和局灶性结节增生(2.5%vs.0.4%；OR6.9）。未发现与TXA和合并症的关联。
结论：在这个患有罕见疾病的庞大患者群体中，随访长达43年，我们发现,迄今为止文献中未报道的合并症患病率更高,并且合并症和LTP与AA之间存在关联.
