Proton Pump Inhibitor Use, Hypomagnesemia and Risk of Cardiovascular Diseases: The Atherosclerosis Risk in Communities (ARIC) Study

Mary R. Rooney, Elizabeth J. Bell, Alvaro Alonso, James S. Pankow, Ryan T. Demmer, Kyle D. Rudser, Lin Y. Chen, Pamela L. Lutsey

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Goals: The goal of this study was to evaluate whether proton pump inhibitor (PPI) use is cross-sectionally associated with hypomagnesemia and whether hypomagnesemia mediates the prospective association between PPIs and cardiovascular disease (CVD) risk. Background: Use of PPIs has been associated with hypomagnesemia, primarily in case reports or within insurance databases. Both PPI use and low serum magnesium (Mg) have been associated with modestly higher CVD risk. Yet, the interrelation between PPI use and Mg in relation to CVD risk is unclear. Study: The 4436 Atherosclerosis Risk in Communities participants without prevalent CVD at visit 5 (baseline, 2011-2013) were included. Multivariable relative risk regression was used for cross-sectional analyses between PPI and hypomagnesemia prevalence (≤0.75 mmol/L). Incident CVD (defined by atrial fibrillation, coronary heart disease, CVD mortality, heart failure, stroke) was identified through 2017. Multivariable Cox regression was used to examine the PPI-CVD association. Results: Participants were mean±SD aged 75±5 years; 63% were women, 23% Black, and 24% were PPI users. PPI users had 1.24-fold (95% confidence interval: 1.08-1.44) higher prevalence of hypomagnesemia than nonusers. Over a median 5 years of follow-up, 684 incident CVD events occurred. PPI users had higher CVD risk [hazard ratio (95% confidence interval) 1.31 (1.10-1.57)] than nonusers. The effect estimate was largely unchanged when hypomagnesemia was added to the model as a potential mediator. Conclusions: In this elderly community-based study, PPI users had a higher prevalence of hypomagnesemia than in nonusers. PPI users also had higher CVD risk than nonusers; however, it appears unlikely that hypomagnesemia explains associations of PPIs with CVD risk.

Original languageEnglish (US)
Pages (from-to)677-683
Number of pages7
JournalJournal of clinical gastroenterology
Issue number8
Early online dateSep 2 2020
StatePublished - Sep 1 2021

Bibliographical note

Funding Information:
The Atherosclerosis Risk in Communities Study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under contract nos (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I). This work was also supported by a grant from the National Heart Lung and Blood Institute [T32HL007779 (M.R.R.)] and the American Heart Association [16EIA26410001 (A.A.)].

Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.


  • cardiovascular disease
  • circulating magnesium
  • prospective
  • proton pump inhibitors

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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