Association of baseline and time-varying serum magnesium levels with cardiovascular disease events in SPRINT participants with and without chronic kidney disease

患有或不患有慢性肾病的 SPRINT 参与者中基线和随时间变化的血清镁水平与心血管疾病事件的关联

• 批准号: 9815059
• 负责人: ROBERT Daniel TOTO
• 金额: $ 12.97万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9815059
• 关键词: Albuminuria; Arrhythmia; Biological Markers; Biology; Blood Vessels; Bone Diseases; Cardiomyopathies; Cardiovascular Diseases; Case-Control Studies; Cause of Death; Cell physiology; Cessation of life; Chronic; Chronic Kidney Failure; Clinical Research; Clinical Treatment; Comorbidity; Congestive Heart Failure; Coronary heart disease; Data; Data Set; Dialysis procedure; Disease Progression; Endothelial Cells; Event; Functional disorder; General Population; Glomerular Filtration Rate; Goals; Guidelines; Health; Heart; Heart failure; High Prevalence; Homeostasis; Hormones; Human; Hypertension; Hypomagnesemia; In Vitro; Incidence; Inflammation; Inflammatory; Insulin Resistance; Intake; Intervention; Intervention Studies; Intervention Trial; Kidney; Kidney Diseases; Knowledge; Link; Magnesium; Magnesium Deficiency; Measurement; Metabolic Diseases; Metabolic syndrome; Metabolism; Methodology; Mg supplementation; Minerals; Modeling; Morbidity - disease rate; Myocardial Infarction; Non-Insulin-Dependent Diabetes Mellitus; Observational Study; Outcome; Participant; Pathogenesis; Pathway interactions; Patients; Persons; Phenotype; Phosphorus; Population; Positioning Attribute; Prevalence; Randomized; Randomized Clinical Trials; Risk; Risk Factors; Sampling; Serum; Serum magnesium level observed; Solid; Stroke; Subgroup; Systolic Pressure; Testing; Time; Tubular formation; Vascular calcification; acute coronary syndrome; adjudicate; adverse outcome; arm; attributable mortality; base; blood pressure intervention; burden of illness; calcium disorder; calcium phosphate; cardiovascular disorder risk; cardiovascular risk factor; cofactor; cohort; cost effective; design; disease diagnosis; endothelial dysfunction; epidemiology study; experience; extracellular; follow-up; hazard; high risk; high risk population; hypertension treatment; in vivo; member; mortality; nephrotoxicity; population based; primary outcome; prospective; rate of change; sudden cardiac death; therapy design; treatment arm

Project Summary/Abstract The main goal of our study is to test the association of baseline and time-varying serum magnesium (SMg) levels with major cardiovascular disease (CVD) events in the Systolic Pressure Intervention Trial (SPRINT) participants with and without chronic kidney disease (CKD). Hypomagnesemia has been recognized as a risk factor for CV morbidity and mortality in the general population and in patients with advanced CKD. Low extracellular Mg concentration has also been associated with endothelial cell dysfunction and vascular calcification, pathways that could contribute to CVD burden. Low SMg associates with incidence and progression of CKD via mechanisms that may include increased inflammation, insulin resistance, hypertension, and/or nephrotoxicity. Our study will be the first to specifically assess the association of longitudinal changes in SMg with CVD events in a large US cohort of patients with or without CKD. CVD events (primary outcome) consist of fatal or non-fatal myocardial infarction (MI), stroke, heart failure, non-MI acute coronary syndrome, or death attributable to CVD. A secondary renal outcome will be rate of change in eGFR (eGFR slope) from 6-month post-randomization until the end of follow-up. We expect low SMg to be associated with a higher risk for CV death and events, and a greater longitudinal decrease in eGFR in the SPRINT cohort, particularly in patients with CKD based on the higher prevalence of underlying endothelial dysfunction and comorbidity in this prespecified high-risk subgroup. We aim to test this association with multivariable Cox proportional hazards regression models using baseline and time-varying Mg measurements, and incorporating known and putative confounders. Our study will provide new and important information including data on within-person SMg variability over time, that is critical for the design of cost-effective pragmatic interventional studies of Mg supplementation as an inexpensive therapy to mitigate CVD in high-risk CKD patients.

项目总结/摘要 本研究的主要目的是检测基线和随时间变化的血清镁（SMg）水平之间的关系 心血管压力干预试验（SPRINT）参与者中发生重大心血管疾病（CVD）事件的患者 有和没有慢性肾脏病（CKD）。低镁血症被认为是CV的风险因素 一般人群和晚期CKD患者的发病率和死亡率。低细胞外镁 浓度也与内皮细胞功能障碍和血管钙化有关， 这可能会导致CVD负担。低SMg与CKD的发生和进展相关， 这些机制可能包括炎症增加、胰岛素抵抗、高血压和/或肾毒性。 我们的研究将是第一个专门评估SMg纵向变化与CVD事件之间关系的研究。 在美国一个大型CKD或非CKD患者队列中。CVD事件（主要结局）包括致死性或非致死性 心肌梗死（MI）、中风、心力衰竭、非MI急性冠状动脉综合征或归因于CVD的死亡。 次要肾脏结局为从随机化后6个月至 后续行动的结束。我们预计低SMg与CV死亡和事件的风险较高相关， SPRINT队列中eGFR的纵向下降幅度更大，尤其是基于 在这个预先设定的高危亚组中，基础内皮功能障碍和合并症的患病率较高。 我们的目的是使用基线数据，用多变量考克斯比例风险回归模型检验这种关联。 和随时间变化的Mg测量，并纳入已知和推定的混杂因素。我们的研究将提供 新的重要信息，包括关于随时间变化的人内SMg变异性的数据，这对 镁补充剂作为一种廉价疗法的成本效益实用干预研究的设计， 缓解高风险CKD患者的CVD。