Proton pump inhibitor use and cardiovascular risk, all-cause, and cardiovascular mortality across baseline eGFR categories: a longitudinal study

This longitudinal cohort study aimed to evaluate the associations of proton pump inhibitor (PPI) use and estimated glomerular filtration rate (eGFR) with cardiovascular disease (CVD) risk, all-cause mortality, and cardiovascular mortality. We analysed data from 30,362 National Health and Nutrition Examination Survey participants (mean age: 49.3 ± 17.6 years; 51.1% women) between 2003 and 2018. Participants were categorised into eight subgroups based on PPI use and eGFR categories. CVD risk was assessed using survey-weighted multivariable logistic regression, while mortality was evaluated with Cox proportional hazards models over a median follow-up of 91 months. Analyses were adjusted for numerous potential confounders, with sensitivity analyses validating the results. Compared to nonusers with normal eGFR, PPI users with eGFR < 30 had the highest odds ratio (OR = 9.29, 95% CI: 3.34-25.81, <i>p</i> < 0.001). Furthermore, in a longitudinal follow-up of 30,329 participants, PPI users with eGFR < 30 exhibited the highest hazard ratio for all-cause mortality (HR = 2.75, 95% CI: 1.42-5.44, <i>p</i> = 0.003). For cardiovascular mortality, elevated risk was identified in PPI users with an eGFR < 60 (HR = 2.80, 95% CI: 1.77-4.41, <i>p</i> < 0.001), and this association remained robust using Fine-Gray competing risk models. This study reveals a strong, graded association between PPI use, reduced eGFR, and an increased risk of CVD, all-cause mortality, and cardiovascular mortality. We recommend integrating eGFR into risk-benefit assessments before initiating PPI therapy.