Association between increased iron stores and impaired endothelial function in patients with hereditary hemochromatosis
Association between increased iron stores and impaired endothelial function in patients with hereditary hemochromatosis
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DOI：
10.1016/s0735-1097(02)02611-6
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发表时间：
2002-12-18
影响因子：
24
通讯作者：
Weiss, G
中科院分区：
文献类型：
--
作者：
Gaenzer, H;Marschang, P;Weiss, G
我们研究了遗传性血色素沉着症（HH）患者的铁状态与早期功能和结构血管异常之间的关系。背景铁可能参与动脉粥样硬化的形成，携带与HH相关的基因突变的患者可能有患冠心病的风险。方法我们研究了41例具有C282 Y突变纯合性的HH患者的血管特性，沿着与51名年龄匹配的对照组，通过测定肱动脉的内皮依赖性舒张（EDD）和颈动脉内膜中层厚度（IMT）。结果男性HH患者谁没有接受静脉切开治疗显示减少EDD和增加IMT与对照组和HH患者接受治疗。在女性HH患者中，无论治疗状态如何，血管参数与对照组无差异，这些患者均无严重铁超负荷。在HH患者中，铁负荷增加与EDD减少和IMT增加显著相关。此外，我们发现体内铁储备和氧化应激指标之间呈正相关。当先前未经治疗的男性HH患者在强化静脉切开术治疗后重新研究时，观察到EDD显著改善（治疗前2.6 +/- 1.3%对治疗后5.5 +/- 2.1%，p = 0.0015）。结论内皮功能受损和IMT增加与铁过载相关，随后诱导氧化应激，并且与HH患者的遗传残疾无关。补充铁的治疗可以使内皮功能正常化，从而降低心血管事件的风险。女性患者的风险可能会降低，可能是由于月经持续流失铁。(C)2002年，美国心脏病学会基金会。
OBJECTIVES We studied associations between iron status and early functional and structural vascular abnormalities in patients with hereditary hemochromatosis (HH).BACKGROUND Iron may be involved in atherogenesis, and patients bearing a genetic mutation associated with HH are possibly at risk of developing coronary heart disease.METHODS We studied the vascular properties of 41 HH patients who had homozygosity for the C282Y mutation, along with 51 age-matched control subjects, by determination of endothelium-dependent dilation (EDD) of the brachial artery and intima-media thickness (IMT) of the carotid artery.RESULTS Male HH patients who were not receiving phlebotomy therapy showed a reduced EDD and increased IMT compared with controls and HH patients receiving therapy. In female HH patients, irrespective of treatment status, vascular parameters were not different from those of controls, and none of these patients had severe iron overload. In HH patients, increased iron load was significantly associated with reduced EDD and increased IMT. Moreover, we found a positive correlation between body iron stores and indicators of oxidative stress. When previously untreated male HH patients were re-investigated after intensive phlebotomy therapy, a significant improvement in EDD was observed (2.6 +/- 1.3% before vs. 5.5 +/- 2.1% after treatment, p = 0.0015).CONCLUSIONS Impaired endothelial function and increased IMT are associated with iron overload, with subsequent induction of oxidative stress, and are not linked to a genetic disability in HH patients. Consequent iron-depletion therapy normalizes endothelial function and may thus reduce the increased risk of cardiovascular events. Female patients may be at a reduced risk, presumably due to continuous iron loss by menstruation. (C) 2002 by the American College of Cardiology Foundation.