Serum Mganesium and Cardiovascular Outcomes and Mortality in CKD: The Chronic Renal Insufficiency Cohort (CRIC)

Rationale & Objective: Low serum magnesium level has been shown to be associated with increased mortality, but its role as a predictor of cardiovascular disease is unclear. This study evaluates the association between serum magnesium level and cardiovascular events and all-cause mortality in a large cohort of individuals with chronic kidney disease (CKD). Study Design: Prospective cohort study. Setting & Participants: 3,867 participants with CKD, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Exposure: Serum magnesium measured at study baseline. Outcomes: Composite cardiovascular events (myocardial infarction, cerebrovascular accident, heart failure, and peripheral arterial disease) and all-cause mortality. Analytical Approach: Cox proportional hazards models adjusted for demographic, clinical, and laboratory characteristics. Results: During the 14.6 (4.4) years (standard deviation) of follow-up, 1,384 participants died (36/1,000 person-years), and 1,227 (40/1,000 person-years) had a composite cardiovascular event. There was a nonlinear association between serum magnesium level and all-cause mortality. Low and high magnesium levels were associated with greater rates of all-cause mortality after adjusting for demographics, comorbid conditions, medications including diuretics, estimated glomerular filtration rate, and proteinuria (P < 0.001). No significant associations were observed between serum magnesium levels and the composite cardiovascular events. Low serum magnesium level was associated with incident atrial fibrillation (HR, 1.36; 95% CI, 1.01-1.82; P = 0.04). Limitations: Single measurement of serum magnesium. Conclusions: In this large CKD cohort, serum magnesium level < 1.9 mg/dL and >2.1 mg/dL was associated with increased risk for all-cause mortality. Low magnesium level was associated with incident atrial fibrillation but not with composite cardiovascular disease events. Further studies are needed to determine the optimal range of serum magnesium in CKD to prevent adverse clinical outcomes.