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

TitleProton Pump Inhibitor Use, Hypomagnesemia and Risk of Cardiovascular Diseases: The Atherosclerosis Risk in Communities (ARIC) Study.
Publication TypeJournal Article
Year of Publication2021
AuthorsRooney MR, Bell EJ, Alonso A, Pankow JS, Demmer RT, Rudser KD, Chen LY, Lutsey PL
JournalJ Clin Gastroenterol
Volume55
Issue8
Pagination677-683
Date Published2021 Sep 01
ISSN1539-2031
Abstract

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.

DOI10.1097/MCG.0000000000001420
Alternate JournalJ Clin Gastroenterol
PubMed ID33471493
PubMed Central IDPMC7921206
Grant List16EIA26410001 / AHA / American Heart Association-American Stroke Association / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
HHSN268201700004C / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
T32 HL007779 / HL / NHLBI NIH HHS / United States
HHSN268201700002C / HL / NHLBI NIH HHS / United States
K24 HL148521 / HL / NHLBI NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
HHSN268201700005C / HL / NHLBI NIH HHS / United States
HHSN268201700001C / HL / NHLBI NIH HHS / United States
HHSN268201700003C / HL / NHLBI NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States