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

项目摘要/摘要 我们研究的主要目标是测试基线和时间变化的血清镁(SMG)水平之间的关系 在收缩压干预试验(SPRINT)参与者中发生重大心血管疾病(CVD)事件 有或没有慢性肾脏疾病(CKD)。低镁血症已被认为是心血管疾病的危险因素。 普通人群和晚期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途径有关 这可能会增加心血管疾病的负担。低SMG与CKD的发生和进展 其机制可能包括炎症增加、胰岛素抵抗、高血压和/或肾毒性。 我们的研究将首次具体评估SMG的纵向变化与CVD事件的关联 在美国一大群患有或不患有CKD的患者中。心血管事件(主要结局)包括致命性或非致命性 心肌梗死(MI)、中风、心力衰竭、非MI急性冠脉综合征或可归因于心血管疾病的死亡。 继发性肾脏结局将是从随机化后6个月到 随访期结束。我们预计低SMG与心血管死亡和事件的较高风险相关，并且 Sprint队列中EGFR的纵向下降幅度更大，特别是在CKD患者中 在这一预先确定的高危亚组中，潜在的内皮功能障碍和合并症的患病率更高。 我们的目标是用使用基线的多变量Cox比例风险回归模型来检验这种关联 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，包括关于人内SMG随时间变化的数据，这对 镁补充剂作为一种廉价治疗方法的成本效益实用干预研究设计 减轻高危CKD患者的心血管疾病。

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.