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

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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.