Magnesium modifies the cardiovascular mortality risk associated with hyperphosphatemia in patients undergoing hemodialysis: a cohort study.

Yusuke Sakaguchi,Yoshiharu Tsubakihara,Kunitoshi Iseki,Yoshitaka Isaka,Terumasa Hayashi,Tatsuya Shoji,Hiromi Rakugi,Naohiko Fujii,Rudolf Kirchmair

doi:10.1371/journal.pone.0116273

Abstract

BackgroundIn vitro studies have shown inhibitory effects of magnesium (Mg) on phosphate-induced calcification of vascular smooth muscle cells, raising the possibility that maintaining a high Mg level may be useful for reducing cardiovascular risks of patients with hyperphosphatemia. We examined how serum Mg levels affect the association between serum phosphate levels and the risk of cardiovascular mortality in patients undergoing hemodialysis.MethodsA nationwide register-based cohort study was conducted using database of the Renal Data Registry of the Japanese Society for Dialysis Therapy in 2009. We identified 142,069 patients receiving in-center hemodialysis whose baseline serum Mg and phosphate levels were available. Study outcomes were one-year cardiovascular and all-cause mortality. Serum Mg levels were categorized into three groups (lower, <2.7 mg/dL; intermediate, ≥2.7, <3.1 mg/dL; and higher, ≥3.1 mg/dL).ResultsDuring follow-up, 11,401 deaths occurred, out of which 4,751 (41.7%) were ascribed to cardiovascular disease. In multivariable analyses, an increase in serum phosphate levels elevated the risk of cardiovascular mortality in the lower- and intermediate-Mg groups, whereas no significant risk increment was observed in the higher-Mg group. Moreover, among patients with serum phosphate levels of ≥6.0 mg/dL, the cardiovascular mortality risk significantly decreased with increasing serum Mg levels (adjusted odds ratios [95% confidence intervals] of the lower-, intermediate-, and higher-Mg groups were 1.00 (reference), 0.81 [0.66–0.99], and 0.74 [0.56–0.97], respectively.). An interaction between Mg and phosphate on the risk of cardiovascular mortality was statistically significant (P = 0.03).ConclusionSerum Mg levels significantly modified the mortality risk associated with hyperphosphatemia in patients undergoing hemodialysis.

Highlights

Cardiovascular disease (CVD) is a leading cause of mortality in patients undergoing hemodialysis, accounting for nearly 40% of all deaths [1,2,3,4]
We examined how serum Mg levels affect the association between serum phosphate levels and the risk of cardiovascular mortality in patients undergoing hemodialysis
Among patients with serum phosphate levels of $6.0 mg/dL, the risk for cardiovascular mortality was not significantly different between the very low- and lower-Mg groups, respectively. In this large-scale cohort of hemodialysis patients, we demonstrated that the mortality risk associated with hyperphosphatemia was largely altered by serum Mg levels

Summary

Introduction

Cardiovascular disease (CVD) is a leading cause of mortality in patients undergoing hemodialysis, accounting for nearly 40% of all deaths [1,2,3,4]. The significant association of lower serum Mg with an increased cardiovascular risk is found in patients with pre-dialysis CKD [15] and those undergoing hemodialysis [16]. An increase in serum phosphate levels elevated the risk of cardiovascular mortality in the lowerand intermediate-Mg groups, whereas no significant risk increment was observed in the higher-Mg group. Among patients with serum phosphate levels of $6.0 mg/dL, the cardiovascular mortality risk significantly decreased with increasing serum Mg levels (adjusted odds ratios [95% confidence intervals] of the lower-, intermediate-, and higher-Mg groups were 1.00 (reference), 0.81 [0.66–

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Conclusion