Proton Pump Inhibitor Use and Incident Hypertension in Menopausal Women

Background Proton pump inhibitors (PPIs) could affect blood pressure regulation by suppressing gastric acid required for the conversion of oral nitrite into nitric oxide. Whether PPI use is associated with incident hypertension remains unknown. Methods We included 64 720 menopausal women who were fr...

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Main Authors: Ahmed I. Soliman, Jean Wactawski‐Wende, Amy E. Millen, Shelly L. Gray, Charles B. Eaton, Kathleen M. Hovey, Macarius Donneyong, Nazmus Saquib, Charles P. Mouton, Deepika Laddu, Simin Liu, Daichi Shimbo, Sylvia Wassertheil‐Smoller, Michael J. LaMonte
Format: Article
Language:English
Published: Wiley 2025-07-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.124.040009
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author Ahmed I. Soliman
Jean Wactawski‐Wende
Amy E. Millen
Shelly L. Gray
Charles B. Eaton
Kathleen M. Hovey
Macarius Donneyong
Nazmus Saquib
Charles P. Mouton
Deepika Laddu
Simin Liu
Daichi Shimbo
Sylvia Wassertheil‐Smoller
Michael J. LaMonte
author_facet Ahmed I. Soliman
Jean Wactawski‐Wende
Amy E. Millen
Shelly L. Gray
Charles B. Eaton
Kathleen M. Hovey
Macarius Donneyong
Nazmus Saquib
Charles P. Mouton
Deepika Laddu
Simin Liu
Daichi Shimbo
Sylvia Wassertheil‐Smoller
Michael J. LaMonte
author_sort Ahmed I. Soliman
collection DOAJ
description Background Proton pump inhibitors (PPIs) could affect blood pressure regulation by suppressing gastric acid required for the conversion of oral nitrite into nitric oxide. Whether PPI use is associated with incident hypertension remains unknown. Methods We included 64 720 menopausal women who were free from cardiovascular disease and hypertension at enrollment in the Women's Health Initiative Observational Study (1993–1998). Baseline PPI use and duration were determined using medication inventories. The outcome was physician diagnosed/treated incident hypertension, assessed by self‐report on annual questionnaires. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional hazard models for incident hypertension according to baseline PPI use (no/yes) and duration (<1 year, 1–3 years, >3 years). The association between PPI use and 3‐year changes in measured blood pressure was examined using linear regression. Results There were 28 951 cases of incident hypertension after a mean follow‐up of 8.7 years. PPI use was associated with 17% higher risk of hypertension compared with nonuse in the fully adjusted model (HR, 1.17 [95% CI, 1.08–1.27]). Longer PPI use durations were significantly associated with incrementally higher risk of hypertension (HR, 1.13, 1.17, 1.28, respectively; trend P<0.001). The 3‐year change in multivariable‐adjusted mean systolic blood pressure increased significantly for PPI new users (+3.39 mm Hg, P=0.049) compared with never users. Conclusions PPI use was associated with higher risk of diagnosed hypertension in menopausal women, and the risk showed a significant trend according to longer duration of use. Further studies are needed to confirm these findings.
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spelling doaj-art-5a4e4e1e95d244fab9eb522e097d79482025-08-20T03:34:45ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-07-01141310.1161/JAHA.124.040009Proton Pump Inhibitor Use and Incident Hypertension in Menopausal WomenAhmed I. Soliman0Jean Wactawski‐Wende1Amy E. Millen2Shelly L. Gray3Charles B. Eaton4Kathleen M. Hovey5Macarius Donneyong6Nazmus Saquib7Charles P. Mouton8Deepika Laddu9Simin Liu10Daichi Shimbo11Sylvia Wassertheil‐Smoller12Michael J. LaMonte13Department of Epidemiology and Environmental Health University at Buffalo—SUNY Buffalo NY USADepartment of Epidemiology and Environmental Health University at Buffalo—SUNY Buffalo NY USADepartment of Epidemiology and Environmental Health University at Buffalo—SUNY Buffalo NY USASchool of Pharmacy University of Washington Seattle WA USADepartment of Family Medicine Warren Alpert Medical School of Brown University Pawtucket RI USADepartment of Epidemiology and Environmental Health University at Buffalo—SUNY Buffalo NY USACollege of Pharmacy The Ohio State University Columbus OH USACollege of Medicine Sulaiman AlRajhi University Bukariyah Saudi ArabiaUniversity of Texas Medical Branch Galveston TX USAArbor Research Collaborative for Health Ann Arbor MI USADepartment of Epidemiology &amp; Biostatistics University of California Irvine School of Population and Public Health Irvine CA USADepartment of Medicine Columba University Irving Medical Center New York NY USADepartment of Epidemiology and Population Health Albert Einstein College of Medicine Bronx NY USADepartment of Epidemiology and Environmental Health University at Buffalo—SUNY Buffalo NY USABackground Proton pump inhibitors (PPIs) could affect blood pressure regulation by suppressing gastric acid required for the conversion of oral nitrite into nitric oxide. Whether PPI use is associated with incident hypertension remains unknown. Methods We included 64 720 menopausal women who were free from cardiovascular disease and hypertension at enrollment in the Women's Health Initiative Observational Study (1993–1998). Baseline PPI use and duration were determined using medication inventories. The outcome was physician diagnosed/treated incident hypertension, assessed by self‐report on annual questionnaires. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional hazard models for incident hypertension according to baseline PPI use (no/yes) and duration (<1 year, 1–3 years, >3 years). The association between PPI use and 3‐year changes in measured blood pressure was examined using linear regression. Results There were 28 951 cases of incident hypertension after a mean follow‐up of 8.7 years. PPI use was associated with 17% higher risk of hypertension compared with nonuse in the fully adjusted model (HR, 1.17 [95% CI, 1.08–1.27]). Longer PPI use durations were significantly associated with incrementally higher risk of hypertension (HR, 1.13, 1.17, 1.28, respectively; trend P<0.001). The 3‐year change in multivariable‐adjusted mean systolic blood pressure increased significantly for PPI new users (+3.39 mm Hg, P=0.049) compared with never users. Conclusions PPI use was associated with higher risk of diagnosed hypertension in menopausal women, and the risk showed a significant trend according to longer duration of use. Further studies are needed to confirm these findings.https://www.ahajournals.org/doi/10.1161/JAHA.124.040009blood pressurehypertensionmenopauseproton pump inhibitorswomen
spellingShingle Ahmed I. Soliman
Jean Wactawski‐Wende
Amy E. Millen
Shelly L. Gray
Charles B. Eaton
Kathleen M. Hovey
Macarius Donneyong
Nazmus Saquib
Charles P. Mouton
Deepika Laddu
Simin Liu
Daichi Shimbo
Sylvia Wassertheil‐Smoller
Michael J. LaMonte
Proton Pump Inhibitor Use and Incident Hypertension in Menopausal Women
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
blood pressure
hypertension
menopause
proton pump inhibitors
women
title Proton Pump Inhibitor Use and Incident Hypertension in Menopausal Women
title_full Proton Pump Inhibitor Use and Incident Hypertension in Menopausal Women
title_fullStr Proton Pump Inhibitor Use and Incident Hypertension in Menopausal Women
title_full_unstemmed Proton Pump Inhibitor Use and Incident Hypertension in Menopausal Women
title_short Proton Pump Inhibitor Use and Incident Hypertension in Menopausal Women
title_sort proton pump inhibitor use and incident hypertension in menopausal women
topic blood pressure
hypertension
menopause
proton pump inhibitors
women
url https://www.ahajournals.org/doi/10.1161/JAHA.124.040009
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