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.

项目概要/摘要 我们研究的主要目标是测试基线和随时间变化的血清镁 (SMg) 水平的关联 收缩压干预试验 (SPRINT) 参与者中有重大心血管疾病 (CVD) 事件 有或没有慢性肾脏病（CKD）。低镁血症已被认为是心血管疾病的危险因素 一般人群和晚期 CKD 患者的发病率和死亡率。细胞外镁含量低 浓度还与内皮细胞功能障碍和血管钙化有关 这可能会增加 CVD 负担。低 SMg 与 CKD 的发生和进展相关 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 在美国一大批患有或不患有 CKD 的患者中。 CVD 事件（主要结果）包括致命或非致命 心肌梗塞 (MI)、中风、心力衰竭、非 MI 急性冠脉综合征或 CVD 导致的死亡。 次要肾脏结果是从随机分组后 6 个月到 eGFR 的变化率（eGFR 斜率） 跟进结束。我们预计低 SMg 与较高的心血管死亡和事件风险相关，并且 SPRINT 队列中 eGFR 纵向下降幅度更大，特别是在 CKD 患者中 在这个预先指定的高风险亚组中，潜在内皮功能障碍和合并症的患病率较高。 我们的目标是使用基线测试与多变量 Cox 比例风险回归模型的关联 和随时间变化的镁测量，并结合已知和推定的混杂因素。我们的研究将提供 新的重要信息，包括人体内 SMg 随时间变化的数据，这对于 设计具有成本效益的实用干预研究，将镁补充剂作为一种廉价疗法 减轻高危 CKD 患者的 CVD。