Proton pump inhibitor use and cardiovascular risk, all-cause, and cardiovascular mortality across baseline eGFR...

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, p < 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, p = 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, p < 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.