Markedly impaired fibrinolytic balance contributes to cardiovascular risk in adults with growth hormone deficiency
Markedly impaired fibrinolytic balance contributes to cardiovascular risk in adults with growth hormone deficiency
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DOI：
10.1210/jc.2007-0609
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发表时间：
2007-09-01
影响因子：
5.8
通讯作者：
Vaughan, Douglas E.
中科院分区：
文献类型：
--
作者：
Devin, Jessica K.;Blevins, Lewis S., Jr.;Vaughan, Douglas E.
背景：成人生长激素缺乏症（GHD）有多种心血管危险因素，包括不利的脂质特征和身体组成，以及内皮功能和心脏功能的损害。我们假设GHD与纤溶酶原激活物抑制剂-1 （PAI-1）水平升高有关，PAI-1是循环中纤溶酶原激活的主要抑制剂。目的：该研究的目的是确定成人GHD患者的纤溶特征，并与对照组进行比较。研究设计和参与者：这是一项前瞻性观察性研究，包括12名成人GHD患者。12名性别、年龄和体重指数匹配的成年人作为对照。主要结局指标：主要结局指标为昼夜血浆PAI- 1抗原与相应的组织-纤溶酶原激活物（tPA）活性值。结果：成人GHD表现出不利的24小时纤维蛋白溶解特征，其特征是PAI- 1抗原平均升高62%（调整基线PAI- 1后为2.77 ng/ml, P = 0.049）， tPA活性平均降低24%（调整基线tPA后为- 0.17 IU/ml, P = 0.003）。静脉闭塞后PAI- 1活性持续升高，超过4 IU/ml [7.2 IU/ml（四分位数范围0.8-17.4）]，证明了GHD的纤溶反应存在缺陷；P = 0.018]。通过120秒内血流介导的血管舒张百分比(曲线下面积3.8（四分位数范围-2.4至7.9）vs. 12.8（四分位数范围2.1至19.4）来量化，GHD患者内皮功能受损；P = 0.043]。结论：成人GHD表现出血浆纤溶平衡的改变，包括PAI- 1抗原水平升高和tPA活性降低。这些变化可能导致这一人群心血管发病率的增加。
Context: Adults with GH deficiency (GHD) have multiple cardiovascular risk factors, including an unfavorable lipid profile and body composition as well as impairments in endothelial function and cardiac performance. We hypothesized that GHD is associated with elevated levels of plasminogen activator inhibitor-1 (PAI-1), the major inhibitor of plasminogen activation in the circulation.Objective: The objective of the study was to determine the fibrinolytic profile of adults with GHD in comparison with controls.Study Design and Participants: This was a prospective, observational study including 12 adults with GHD. Twelve gender-, age-, and body mass index-matched adults served as controls.Main Outcome Measures: The primary outcome measures were circadian plasma PAI- 1 antigen with corresponding tissue-plasminogen activator (tPA) activity values. Endothelial function was assessed by flow-mediatedResults: Adults with GHD exhibited an unfavorable 24-h fibrinolytic profile characterized by a mean 62% elevation in PAI- 1 antigen (2.77 ng/ml after adjustment for baseline PAI- 1; P = 0.049) in the setting of a mean 24% reduction in tPA activity (- 0.17 IU/ml after adjustment for baseline tPA; P = 0.003). Fibrinolytic response was defective in GHD, as demonstrated by a sustained elevation in PAI- 1 activity greater than 4 IU/ml after venous occlusion [7.2 IU/ml ( interquartile range 0.8-17.4); P = 0.018]. Endothelial function was impaired in GHD, as quantified by percent flow-mediated vasodilation over 120 sec [ area under the curve 3.8 ( interquartile range -2.4 to 7.9) vs. 12.8 ( interquartile range 2.1-19.4); P = 0.043].Conclusions: Adults with GHD demonstrate alterations in plasma fibrinolytic balance, including elevated levels of PAI- 1 antigen with decreased tPA activity. These changes may contribute to the increased cardiovascular morbidity within this population.