CLINICAL TRIAL: CAN THE HEART BE PROTECTED FROM HYPERLIPIDEMIA? GSD & ATHEROSCL

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 糖原贮积症是一种糖原代谢紊乱，可导致低血糖、乳酸血症、高尿酸血症、高脂血症等。1987年。虽然GSD患者表现出以高胆固醇血症、高甘油三酯血症和低密度脂蛋白为特征的促动脉粥样硬化的血脂特征，但严重的高脂血症尚未与早期心血管疾病风险的增加相关。因此，目前的护理标准不建议使用降脂剂Ubels等人进行治疗。2002年。已经有几种理论来解释GSD患者的保护特征，如增加胆固醇外流，增加抗氧化潜力，以及降低血小板聚集性等。2005年，维滕斯坦等人。2002年，Muhlhausen等人。2005年。尽管存在血脂异常，但还没有全面的研究来充分评估GSD患者的心血管风险。我们假设高脂血症会增加GSD患者患早期心血管疾病的风险。使用颈动脉内膜中层厚度IMT、肱动脉反应性条和大鼠放射状动脉眼压计对CVD进行无创性测量。2001年将对100例GSD合并高脂血症患者进行检查。BAR将成为CVD的主要结果衡量标准。我们将通过测量载脂蛋白、游离脂肪酸、单一血浆抗氧化剂和凝血参数来评估所提出的保护机制。如果有证据表明这些拟议的机制确实具有保护性，这项研究的数据可能会推广到其他人群的心血管疾病预防。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Glycogen Storage Disease GSD is a disorder of glycogen metabolism which results in hypoglycemia, lactic acidemia, hyperuricemia and hyperlipidemia Levy et al. 1987. While GSD patients manifest a pro-atherogenic lipid profile characterized by hypercholesterolemia, hypertriglyceridemia, and reduced HDL, the severe hyperlipidemia has not yet been correlated with an increased risk of early cardiovascular disease CVD. Consequently, the current standard of care does not recommend treatment with lipid lowering agents Ubels et al. 2002. Several theories have been postulated to explain the protective features in GSD patients such as increased cholesterol efflux, increased antioxidant potential, and decreased platelet aggregation Nguyen et al. 2005, Wittenstein et al. 2002, Muhlhausen et al. 2005. Despite the presence of dyslipidemia, there has been no comprehensive study to adequately assess cardiovascular risk in GSD patients. We hypothesize that hyperlipidemia places GSD patients at increased risk for early cardiovascular disease. Noninvasive measures of CVD using carotid intima media thickness IMT, brachial artery reactivity BAR, and radial artery tonometry RAT Fathi et al. 2001 will be performed on 100 patients with GSD and hyperlipidemia. BAR will be the primary outcome measurement of CVD. We will evaluate the proposed protective mechanisms with by measuring Apo proteins, free fatty acids, single plasma antioxidants and coagulation parameters. The data from this study may be generalized to CVD prevention in other populations if there is evidence that these proposed mechanisms are indeed protective.