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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 糖原累积病GSD是一种糖原代谢紊乱，可导致低血糖、乳酸血症、高尿酸血症和高脂血症Levy et al. 1987。 虽然GSD患者表现出以高胆固醇血症、高甘油三酯血症和HDL降低为特征的促动脉粥样硬化脂质谱，但重度高脂血症尚未与早期心血管疾病CVD的风险增加相关。 因此，现行标准治疗不推荐使用降脂药治疗Ubels et al. 2002。 已经提出了几种理论来解释GSD患者的保护性特征，如胆固醇流出增加、抗氧化潜力增加和血小板聚集减少Nguyen et al. 2005，维滕施泰因et al. 2002，Muhlhausen et al. 2005。 尽管存在血脂异常，但目前还没有全面的研究来充分评估GSD患者的心血管风险。 我们假设高脂血症使GSD患者早期心血管疾病的风险增加。 采用颈动脉内膜中层厚度IMT、肱动脉反应性BAR和桡动脉张力测定法（RAT Fathi et al. 2001）对100例GSD和高脂血症患者进行CVD的无创测量。 BAR将是CVD的主要结局指标。 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提出的机制确实具有保护作用，则本研究的数据可推广到其他人群的CVD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.