Szegedi Róbert, Széplaki Gábor, Varga Lilian, Prohászka Zoltán, Széplaki Zoltán, Karádi István, Füst George, Farkas Henriette
Department of Neurology, Kútvölgyi Clinical Centre, Semmelweis University, Budapest, Hungary.
Atherosclerosis. 2008 May;198(1):184-91. doi: 10.1016/j.atherosclerosis.2007.09.025. Epub 2007 Oct 30.
Hereditary angioedema (HAE) is characterized by episodic edematous attacks due to the deficiency of the C1-inhibitor (C1-INH). Recently, we have described that the long-term use of danazol affects lipid metabolism, resulting in decreased high-density lipoprotein (HDL) and increased low-density lipoprotein (LDL) cholesterol levels, which might lead to accelerated, early atherosclerosis. Our aim in the present study was to investigate the impact of danazol treatment on the risk of atherosclerosis in HAE patients.
The prevalence of vascular disease, as well as carotid intima-media thickness (IMT)--an objective marker of atherosclerosis--was determined in 32 HAE patients undergoing danazol prophylaxis, and compared to 25 HAE patients without danazol treatment, as well as to 20 healthy controls. Distinct atherosclerosis risk profiles were determined in addition.
HAE patients with danazol prophylaxis had higher body mass index (p=0.0055 and 0.0020), creatinine (p=0.0001 and 0.0130), alanine aminotransferase (p=0.0298 and 0.0457), LDL (p=0.0060 and <0.0001) and decreased HDL (p<0.0001 and <0.0001) levels compared to both control groups. The prevalence of vascular diseases did not differ in the two patient groups. No significant differences were observed in mean (0.43 (0.37-0.50)mm vs. 0.40 (0.35-0.49)mm, p=0.5465) carotid IMT values, when comparing patients with or without long-term danazol prophylaxis.
Thickening of IMT due to danazol use was not observed in HAE patients. We hypothesize that the functional deficiency of C1-INH might confer protection against atherosclerosis in these patients.
遗传性血管性水肿(HAE)的特征是由于C1抑制因子(C1-INH)缺乏而导致的发作性水肿发作。最近,我们描述了达那唑的长期使用会影响脂质代谢,导致高密度脂蛋白(HDL)降低和低密度脂蛋白(LDL)胆固醇水平升高,这可能会导致动脉粥样硬化加速和早期发生。我们在本研究中的目的是调查达那唑治疗对HAE患者动脉粥样硬化风险的影响。
在32名接受达那唑预防治疗的HAE患者中确定血管疾病的患病率以及颈动脉内膜中层厚度(IMT)——动脉粥样硬化的一个客观指标,并与25名未接受达那唑治疗的HAE患者以及20名健康对照进行比较。此外,还确定了不同的动脉粥样硬化风险概况。
与两个对照组相比,接受达那唑预防治疗的HAE患者的体重指数(p = 0.0055和0.0020)、肌酐(p = 0.0001和0.0130)、丙氨酸转氨酶(p = 0.0298和0.0457)、LDL(p = 0.0060和<0.0001)更高,HDL降低(p<0.0001和<0.0001)。两个患者组中血管疾病的患病率没有差异。在比较长期接受达那唑预防治疗和未接受该治疗的患者时,颈动脉IMT值的平均值没有显著差异(0.43(0.37 - 0.50)mm对0.40(0.35 - 0.49)mm,p = 0.5465)。
在HAE患者中未观察到达那唑使用导致的IMT增厚。我们推测C1-INH的功能缺陷可能使这些患者免受动脉粥样硬化的影响。