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

用烟酸提高 HDL-C 是否可以改善早期 CKD 的内皮功能？

• 批准号: 7387961
• 负责人: Vandana Menon
• 金额: $ 25.21万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7387961
• 关键词: 2-tyrosine; 3-nitrotyrosine; Achievement; Address; Apolipoprotein A-I; Apolipoproteins B; Attenuated; C-reactive protein; Cardiotonic Agents; Cardiovascular Diseases; Chronic Kidney Failure; Clinical; Clinical Practice Guideline; Clinical Research; Clinical Trials; Coronary; Coronary Circulation; Coronary heart disease; Data; Development; Diabetes Mellitus; Disease Marker; Double-Blind Method; Dyslipidemias; Elevation; Epidemiologic Studies; Epidemiology; Event; Functional disorder; Future; General Population; Glomerular Filtration Rate; Goals; High Density Lipoprotein Cholesterol; High Density Lipoproteins; High Prevalence; Impairment; Inflammation; Inflammatory; Interleukin-6; Kidney; Kidney Diseases; LDL Cholesterol Lipoproteins; Lead; Lipids; Lipoprotein (a); Lipoprotein (a-); Lipoproteins; Low-Density Lipoproteins; Measures; Mediating; Microalbuminuria; Morbidity - disease rate; NIH Program Announcements; Nicotinic Acids; Nitric Oxide Synthase; Oxidative Stress; Pathway interactions; Patients; Peripheral; Pilot Projects; Placebos; Population; Preventive Intervention; Principal Investigator; Public Health; Randomized; Randomized Controlled Trials; Research; Risk; Risk Factors; Risk Reduction; Staging; Stratification; Testing; Thinking; Translational Research; Triglycerides; Tyrosine; Vascular Cell Adhesion Molecule-1; Vascular Endothelium; Very low density lipoprotein; Week; Woman; brachial artery; cardiovascular disorder risk; cytokine; hydroxyoctadecadienoic acid; improved; insight; interest; men; mortality; placebo controlled study; research study; vascular endothelial dysfunction

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.

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.