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

> **NIH NIH R21** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $127,131

## Abstract

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.

## Key facts

- **NIH application ID:** 9969599
- **Project number:** 5R21HL145424-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** ROBERT Daniel TOTO
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $127,131
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969599

## Citation

> US National Institutes of Health, RePORTER application 9969599, Association of baseline and time-varying serum magnesium levels with cardiovascular disease events in SPRINT participants with and without chronic kidney disease (5R21HL145424-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9969599. Licensed CC0.

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