Does Raising HDL-C with Niacin Improve Endothelial Function in Early CKD?

描述（由申请人提供）：心血管疾病（CVD）是导致慢性肾脏疾病（CKD）死亡的主要原因。低高密度脂蛋白胆固醇（HDL- c）是心血管疾病的危险因素，与炎症、氧化应激和内皮功能障碍增加有关。对低HDL-C患者的研究表明，HDL-C适度升高可显著降低心血管疾病风险。外周血管内皮功能障碍是冠状血管内皮功能受损的标志，与CVD风险增加有关。在CKD中，低HDL-C和内皮功能受损的发生率很高。因此，CKD的部分CVD风险可能是由内皮功能障碍介导的，并可能通过提高HDL-C水平来减轻。烟酸是提高HDL-C水平最有效的药物，似乎可以改善非CKD患者的内皮功能。鉴于低HDL-C和内皮功能障碍在CKD患者中的高患病率，针对HDL-C的改善在这一人群中特别有意义，特别是在CKD早期阶段的患者，他们最有可能从预防性干预中受益。关于烟酸提高CKD患者HDL-C水平的有效性以及这一高危人群中HDL-C与内皮功能之间的关系的数据有限。我们建议在80例2-3期CKD和低HDL-C水平患者中进行一项试点随机对照研究。总的研究假设是，在早期CKD患者中，烟酸治疗提高HDL-C水平可能通过减少炎症和氧化应激来改善内皮功能。具体目标1：为未来的研究收集试点数据，以确定烟酸治疗是否与早期CKD较高的HDL-C水平和内皮功能改善有关。我们将在基线和烟酸治疗12周后评估HDL-C和其他脂蛋白参数的水平及其与内皮功能的关系（用肱动脉反应性测量）。具体目的2：收集初步数据，研究内皮功能改善的机制。我们将研究HDL-C变化与炎症和氧化应激标志物水平之间的关系，以及它们与内皮功能变化的关系。这项研究的结果将为烟酸作为CKD的心脏保护剂的效用提供重要的见解。公共卫生相关性：心血管疾病（CVD）是慢性肾脏疾病（CKD）死亡的主要原因。低高密度脂蛋白胆固醇（HDL- c）是心血管疾病的危险因素，与炎症、氧化应激和内皮功能障碍增加有关。烟酸是提高HDL-C水平和改善非ckd患者内皮功能最有效的药物。鉴于低HDL-C和内皮功能障碍在CKD患者中的高患病率，针对HDL-C的改善在这一人群中特别有意义，特别是在CKD早期阶段的患者，他们最有可能从预防性干预中受益。这项初步研究的结果将为烟酸作为慢性肾病的心脏保护剂的效用提供重要的见解。

DESCRIPTION (Provided by applicant): Cardiovascular disease (CVD) is the leading cause of mortality in chronic kidney disease (CKD). Low HDL- cholesterol (HDL-C) is a risk factor for CVD and is associated with increased inflammation, oxidative stress and endothelial dysfunction. Studies in patients with low HDL-C have shown significant CVD risk reduction with modest elevations in HDL-C. Peripheral vascular endothelial dysfunction is a marker for impaired endothelial function in the coronary vasculature and is associated with increased CVD risk. There is a high prevalence of low HDL-C and impaired endothelial function in CKD. Thus, part of the excess CVD risk in CKD may be mediated by endothelial dysfunction and may potentially be mitigated by raising HDL-C levels. Niacin is the most effective agent available to increase HDL-C levels and appears to improve endothelial function in non- CKD patients. Given the high prevalence of low HDL-C and endothelial dysfunction in patients with CKD, targeting improvement in HDL-C is of particular interest in this population especially in patients in the earlier stages of CKD who may be most likely to benefit from preventive interventions. There are limited data regarding the efficacy of niacin in raising HDL-C levels in patients with CKD and on the relationship between HDL-C and endothelial function in this high-risk population. We propose a pilot randomized controlled study in 80 patients with Stage 2-3 CKD and low HDL-C levels. The overall study hypothesis is that raising HDL-C levels with niacin therapy is associated with improvements in endothelial function potentially by reducing inflammation and oxidative stress, in patients in the earlier stages of CKD. Specific Aim 1: To collect pilot data for future studies to determine whether niacin therapy is associated with higher HDL-C levels and improvements in endothelial function in the earlier stages of CKD. We will evaluate levels of HDL-C and other lipoprotein parameters and their relationship with endothelial function (measured using brachial artery reactivity) at baseline and after a 12 week course of niacin. Specific Aim 2: To collect preliminary data to examine mechanisms underlying the improvements in endothelial function. We will examine the relationship between changes in HDL-C and levels of markers of inflammation and oxidative stress and how they relate to changes in endothelial function. The results of this study will provide important insights into the utility of niacin as a cardioprotective agent in CKD. PUBLIC HEALTH RELEVANCE: Cardiovascular disease (CVD) is the leading cause of mortality in chronic kidney disease (CKD). Low HDL- cholesterol (HDL-C) is a risk factor for CVD and is associated with increased inflammation, oxidative stress and endothelial dysfunction. Niacin is the most effective agent available to increase HDL-C levels and appears to improve endothelial function in non-CKD patients. Given the high prevalence of low HDL-C and endothelial dysfunction in patients with CKD, targeting improvement in HDL-C is of particular interest in this population especially in patients in the earlier stages of CKD who may be most likely to benefit from preventive interventions. The results of this pilot study will provide important insights into the utility of niacin as a cardioprotective agent in CKD.