Abstract Body (Do not enter title and authors here): Background:
Proton pump inhibitors (PPIs) are commonly prescribed for acid-related conditions, especially in patients with cardiovascular risk factors. Although widely considered safe, emerging evidence suggests potential associations with adverse vascular outcomes. The impact of chronic PPI use on clinical outcomes among patients undergoing coronary artery calcium (CAC) imaging is not well characterized.

Objective:
To assess whether chronic PPI use is associated with adverse cardiovascular outcomes in adults undergoing CAC imaging.

Methods:
We conducted a retrospective cohort study using the TriNetX Research Network. Adults ≥18 years with ≥2 CAC-related cardiac CT scans (CPT 75571–75574) were included. Patients with prior coronary artery disease, MI, coronary revascularization, chronic kidney disease stage ≥4, malignancy, or H2 receptor antagonist use were excluded. Two cohorts were defined: chronic PPI users and non-users. After 1:1 propensity score matching on age, sex, hypertension, diabetes, obesity, smoking, and hyperlipidemia, each cohort included 4,346 patients. Outcomes included ischemic stroke, MI, and all-cause mortality. Survival analyses were conducted using Kaplan-Meier curves and Cox proportional hazards models.

Results:
Following matching, baseline characteristics were balanced. Over a median follow-up of approximately 1.4 years, all-cause mortality was significantly higher among PPI users (3.0%) compared to non-users (0.9%) (hazard ratio [HR] 0.329, 95% CI: 0.232–0.468, p<0.001). Ischemic stroke was also more frequent in the PPI group (3.3% vs. 1.6%; HR 0.513, 95% CI: 0.385–0.682, p<0.001). MI incidence did not differ significantly (3.6% vs. 3.2%, p=0.408). No coronary revascularization events were reported in either cohort.

Conclusion:
In patients undergoing CAC imaging, chronic PPI use was associated with increased risk of all-cause mortality and ischemic stroke, but not MI. These findings suggest potential long-term cardiovascular risks of PPI therapy in at-risk populations and support the need for further prospective evaluation.

Relevance to Cardiology:
PPIs are often co-prescribed in cardiology, especially in patients on antiplatelet therapy. This study raises concern about their long-term cardiovascular safety and underscores the importance of judicious PPI use in preventive cardiology.