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

Abstract

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. Exposures 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.

Association of serum magnesium with metabolic syndrome and the role of chronic kidney disease: A population‐based cohort study with Mendelian randomization

“…In line with this, a prospective cohort study in 5044 participants demonstrated a nonlinear relationship of serum magnesium with diabetes and insulin resistance 47 . On the other hand, Negrea et al found that serum magnesium <1.9 mg/dL and >2.1 mg/dL was associated with all‐cause mortality in a large cohort of patients with CKD 48 …”

Gla-Rich Protein, Magnesium and Phosphate Associate with Mitral and Aortic Valves Calcification in Diabetic Patients with Moderate CKD

“…Here we show that GRP serum levels are positively associated with Mg, a known vascular calcification inhibitor [ 34 , 35 ]. The importance of P and Mg in vascular calcification and cardiovascular risk have been extensively demonstrated at both epidemiological and mechanistic levels, both in the general population and CKD, with hyperphosphatemia and hypomagnesia associated with increased vascular calcification, cardiovascular events and mortality [ 34 , 35 , 36 , 37 , 38 , 39 ]. In relation to VC, hyperphosphataemia has been associated with aortic and mitral valves calcification, including in moderate CKD patients [ 12 , 40 , 41 , 42 , 43 ].…”

Serum Magnesium, Blood Pressure, and Risk of Hypertension and Chronic Kidney Disease Progression in the CRIC Study

“…15 Lastly, in patients with CKD, in the multiethnic DHS (Dallas Heart Study) cohort, over 12.3 years median follow-up, low serum magnesium (<0.8 mmol/L) was independently associated with all-cause mortality 13 ; and more recently, an analysis from CRIC demonstrated that serum magnesium levels <1.9 mg/dL and >2.1 mg/dL were associated with an increased risk of all-cause mortality. 35 Multiple mechanisms may explain the associations between magnesium and CVD. Magnesium antagonizes voltage-dependent L-type calcium channels in vascular smooth muscles cells, thereby inhibiting calcium influx and leading to reduced vascular tone.…”

“…15 Lastly, in patients with CKD, in the multiethnic DHS (Dallas Heart Study) cohort, over 12.3 years median follow-up, low serum magnesium (<0.8 mmol/L) was independently associated with all-cause mortality 13 ; and more recently, an analysis from CRIC demonstrated that serum magnesium levels <1.9 mg/dL and >2.1 mg/dL were associated with an increased risk of all-cause mortality. 35…”