Phosphorus and Vitamin D Metabolism and Cardiovascular Outcomes: The MESA Study

磷和维生素 D 代谢与心血管结局：MESA 研究

• 批准号: 8250476
• 负责人: BRYAN R KESTENBAUM
• 金额: $ 51.21万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8250476
• 关键词: 25-hydroxyvitamin D; Address; Atherosclerosis; Biological Markers; Blood Pressure; Calcified; Calcium; Cardiac Myocytes; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cells; Cessation of life; Chronic Kidney Failure; Clinical; Clinical Data; Clinical Trials; Communities; Disease; Disease Outcome; Disease Pathway; Ethnic Origin; Evaluation; Event; Exclusion; Functional disorder; Goals; Growth; Health; Hormones; Human; Hypertension; Intervention; Knowledge; Laboratories; Left Ventricular Hypertrophy; Left Ventricular Mass; Link; Measurement; Measures; Medial; Medical; Medicine; Metabolic; Metabolic Diseases; Metabolic Pathway; Metabolism; Minerals; Organ; Osteoblasts; Outcome; Parathyroid gland; Participant; Pathway interactions; Phosphorus; Physiological Processes; Population; Population Heterogeneity; Population Sciences; Preventive Intervention; Race; Renin-Angiotensin-Aldosterone System; Risk Factors; Sampling; Serum; Testing; Therapeutic Intervention; Thoracic aorta; Time; Translations; Urine; Vascular Diseases; Vascular Smooth Muscle Tissue; Vitamin D; Vitamin D Deficiency; Woman; adjudicate; adverse outcome; arterial stiffness; base; calcification; cardiovascular disorder risk; clinical application; clinically relevant; coronary artery calcification; cytokine; fibroblast growth factor 23; follow-up; men; mortality; novel; premature; prevent; public health relevance; transmission process

DESCRIPTION (provided by applicant): Evolving evidence suggests that phosphorous excess and vitamin D insufficiency contribute to cardiovascular disease (CVD) and premature death. Phosphorous excess directly transforms vascular smooth muscle tissue into osteoblast-like cells, which calcify the medial vessel wall. Vitamin D insufficiency activates the renin-angiotensin-aldosterone system, stimulates atherogenic cytokine expression, and directly promotes cardiomyocyte growth. Important gaps in existing knowledge constrain full understanding of mineral metabolism-CVD relationships in humans. First, current ascertainment of the phosphorous and vitamin D metabolic axes is crude, obscuring relationships with CVD outcomes and impeding translation to clinical application. Second, CVD pathways through which disturbed mineral metabolism may promote CVD are incompletely evaluated in humans. Third, phosphorous and vitamin D metabolism vary strongly by race/ethnicity, but knowledge of cardiovascular consequences of mineral metabolism disorders derive from populations with limited diversity. The overall goal of this proposal is to define relationships of phosphorous excess and vitamin D insufficiency with pathophysiologically relevant clinical and subclinical CVD outcomes in a community based, multi-ethnic population. We will characterize the phosphorous and vitamin D metabolic axes using multiple serum and urine biomarkers measured from previously collected baseline samples obtained from 6,736 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). MESA offers a unique opportunity to comprehensively evaluate novel CVD risk factors because of its multi-ethnic sampling strategy, exclusion of clinical CVD at baseline, state-of-the-art subclinical CVD measurements, and adjudicated cardiovascular events. We hypothesize that biomarkers of phosphorous excess (higher concentrations of serum phosphorous, serum fibroblast growth factor-23, and urine phosphorous) and vitamin D deficiency (lower 25- hydroxyvitamin D and higher parathyroid hormone concentrations) will be associated with incident cardiovascular events, incident hypertension, and incident chronic kidney disease. We further hypothesize that biomarkers of phosphorous excess and vitamin D deficiency will be associated with subclinical cardiovascular disease measurements that are directly relevant to mineral metabolism: coronary artery calcification, thoracic aorta calcification, arterial stiffness, and left ventricular mass. PUBLIC HEALTH RELEVANCE: Cardiovascular diseases (CVD) are the major cause of eath in the industrialized world for both men and women. Disturbances in phosphorous and vitamin D metabolism may be novel risk factors for CVD and may offer new opportunities for preventive or therapeutic intervention. The proposed studies will determine whether phosphorus excess and vitamin D deficiency are linked with clinically relevant CVD in a racially and ethnically diverse population. Findings will help clarify optimal serum concentrations of phosphorous and vitamin D biomarkers with respect to cardiovascular health and inform clinical trials which target mineral metabolism to prevent and reduce CVD.

描述（由申请人提供）：不断发展的证据表明，磷过量和维生素D功能不全有助于心血管疾病（CVD）和过早死亡。磷的多余物质直接将血管平滑肌组织转化为成骨细胞样细胞，从而钙化内侧血管壁。维生素D不足会激活肾素 - 血管紧张素 - 醛固酮系统，刺激动脉粥样硬化的细胞因子表达，并直接促进心肌细胞生长。 现有知识中的重要差距限制了对人类矿物代谢-CVD关系的完全理解。首先，当前对磷和维生素D代谢轴的确定是粗略的，掩盖了与CVD结局的关系，并阻碍了转化为临床应用。其次，在人类中不完全评估矿物质代谢可能促进CVD的CVD途径。第三，磷和维生素D代谢因种族/种族而异，但是对矿物质代谢疾病的心血管后果的知识是从多样性有限的种群中得出的。 该提案的总体目的是在一个基于社区的多种族人群中定义磷过量和维生素D不足与病理生理相关的临床和亚临床CVD结果的关系。我们将使用从先前收集的基线样品中测量的多种血清和尿液生物标志物来表征磷酸和维生素D代谢轴，这些基线样品是从6,736名参与者中获得的动脉粥样硬化研究（MESA）。 MESA提供了一个独特的机会，可以全面评估新型CVD风险因素，因为其多种族抽样策略，在基线上排除临床CVD，最先进的亚临床CVD测量以及裁决的心血管事件。我们假设磷酸过多的生物标志物（较高浓度的血清磷，血清成纤维细胞生长因子-23和尿磷）和维生素D缺乏症（低25-羟基羟基抗毒素D和较高的副甲状旁腺激素浓度）将与事件性心血管疾病事件相关，并与心血管疾病事件相关。我们进一步假设，磷过量和维生素D缺乏的生物标志物将与与矿物质代谢直接相关的亚临床心血管疾病测量结果：冠状动脉钙化，胸主动脉钙化，动脉僵硬，动脉僵硬和左心肿块。 公共卫生相关性：心血管疾病（CVD）是男性和女性工业化世界中eath的主要原因。磷和维生素D代谢的障碍可能是CVD的新风险因素，可能为预防或治疗干预提供新的机会。拟议的研究将确定在种族和种族多样性的种群中，磷过量和维生素D缺乏是否与临床相关的CVD有关。研究结果将有助于阐明有关心血管健康的最佳磷酸和维生素D生物标志物的最佳血清浓度，并为临床试验提供了针对矿物质代谢的临床试验，以预防和减少CVD。