Studies on Serial Phlebotomy in Voluntary Blood Donors

无偿献血者连续放血的研究

• 批准号: 7460980
• 负责人: STUART D KATZ
• 金额: $ 38.12万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-11 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7460980
• 关键词: Accounting; Age; American; Biochemical; Biological; Blood; Blood Donations; Blood Plasma Volume; Blood Vessels; Blood Volume; Blood donor; Cardiovascular Diseases; Cardiovascular system; Cross-Sectional Studies; Data; Double-Blind Method; Erythrocytes; Erythropoietin; Event; Excision; Food; Frequencies; Goals; Health; Hemochromatosis; Hemorrhage; Hereditary Disease; Hyperhomocysteinemia; Intervention Studies; Intravenous; Invasive; Iron; Knowledge; Lead; Life; Linear Regressions; Link; Measures; Mediating; Mediator of activation protein; Medical; Modeling; Morbidity - disease rate; Observational Study; Oxidative Stress; Physiological; Policies; Population; Procedures; Public Policy; Randomized; Recommendation; Regulation; Relative (related person); Replacement Therapy; Research Design; Risk; Screening procedure; Serum; Testing; Time; Upper arm; Vascular blood supply; Venous blood sampling; Week; Woman; brachial artery; cardiovascular risk factor; dietary supplements; improved; insight; mortality; novel; prospective; response; shear stress; urinary

DESCRIPTION (provided by applicant): Sullivan first proposed in 1981 that reduction in body iron stores may protect against cardiovascular disease. Blood donation is known to reduce iron stores and has been tentatively associated with reduced cardiovascular risk in observational studies, but the mechanisms to account for this finding are not well characterized. Our preliminary data demonstrate that high-frequency blood donation is associated with severe reductions in iron stores, decreased oxidative stress, and improved vascular endothelial function when compared with sporadic donation. Since improved vascular endothelial function is known to be associated with decreased cardiovascular morbidity and mortality, these preliminary data support a potential mechanistic link between blood donation and reduced cardiovascular risk. We now propose a prospective interventional trial to investigate potential mechanisms linking blood donation and vascular endothelial function in voluntary blood donors. We hypothesize that serial phlebotomy is associated with improved vascular function related to physiological and biochemical effects of iron removal and blood removal. To test this hypothesis, 150 iron-replete voluntary blood donors currently deferred from active donation for non-medical reasons will be randomly assigned to 3 treatment groups: four 500 ml phlebotomy procedures over 6 months without replacement of lost iron, four 500 ml phlebotomy procedures over 6 months with intravenous replacement of lost iron, or sham phlebotomy. This 3-arm study design provides the means to distinguish the relative contributions of blood loss vs. iron loss on biological responses to serial phlebotomy. Flow-mediated dilation in the brachial artery (a non-invasive measure of vascular endothelial function) in the basal state and in response to transient hyperhomocysteinemia, serum and urinary measures of iron stores and oxidative stress, red cell and plasma volume, regional arterial wall shear stress, and erythropoietin levels will be obtained before and after the assigned study intervention. Mulitvariate mixed effects models will be used to determine the association between study treatment and vascular function and whether physiological and biochemical correlates of iron and blood removal are mediators of this association. This study will provide new insight into the relationship between iron stores and vascular function and will provide new data on the health effects of blood donation that could impact the nation's blood supply. More than 50% of all Americans will require a blood donation at least one time in their lives. We propose a prospective randomized double-blind study to determine the effects of blood donation on vascular function. The overall goal of the proposal is to better characterize the potential impact of blood donation on cardiovascular health. The findings of this study will provide novel data that could favorably impact the nation's blood supply, and could influence public policy decisions on screening for hemochromatosis (one of the most common genetic diseases in the US) and regulation of iron content in nutritional supplements and foods.

描述（由申请人提供）：沙利文在1981年首次提出，人体铁储存的减少可能可以预防心血管疾病。已知血液捐赠可以减少铁储存量，并且与观察性研究中的心血管风险降低有关，但是考虑到这一发现的机制并没有很好地表征。我们的初步数据表明，与零星捐赠相比，高频血液捐赠与铁储存量的严重减少，氧化应激减少以及提高血管内皮功能有关。由于已知改善的血管内皮功能与心血管发病率和死亡率降低有关，因此这些初步数据支持血液捐赠与降低心血管风险之间的潜在机械联系。现在，我们提出了一项前瞻性介入试验，以研究将献血和血管内皮功能联系起来的潜在机制。我们假设系列静脉切开术与改善与铁去除铁和除血的生理和生化作用有关的血管功能有关。为了检验这一假设，由于非医学原因，目前从积极捐赠中推迟的150个铁匠自愿献血者将随机分配给3个治疗组：在6个月内进行了四个500 ml 500 ml静脉切开术程序，而无需替换铁失去的铁，四个500 ml 500 ml phlebotsome手术在6个月内，在6个月内，在6个月内丢失了失去的铁photecort of Iron of Iron of Iron of Iron of Iral phlebot of Shams phlebot of Shams phlebot。这项三臂研究设计提供了区分失血与铁损失对生物学静脉切开术的相对贡献的方法。肱动脉中流介导的流动介导的扩张（一种非侵入性血管内皮功能的测量）以及对瞬时性高肌细胞质血症，铁储存的血清和尿液储存，红细胞和血浆的氧化应激，红细胞和等离子体体积，区域动脉壁应力的压力，以及在不适用的均应分配的氧化应激和氧化应激量的响应。 MulitVariate混合效应模型将用于确定研究治疗与血管功能之间的关联，以及铁和除血的生理和生化相关性是否是该关联的介体。这项研究将为铁储存与血管功能之间的关系提供新的见解，并将提供有关血液捐赠的健康影响的新数据，这些数据可能会影响该国血液供应。超过50％的美国人至少需要一次献血。我们提出了一项前瞻性随机双盲研究，以确定捐献血液对血管功能的影响。该提案的总体目标是更好地表征捐献血液对心血管健康的潜在影响。这项研究的发现将提供可能有利的数据，这些数据可能会对美国的血液供应有利，并可能影响筛查血色素症（美国最常见的遗传疾病之一）的公共政策决策，并在营养补充剂和食物中调节铁含量。