Authors

• Admira Bilalić — University Hospital Centre Split, Split, Croatia — ORCID: 0000-0001-6204-1260
• Josip Anđelo Borovac — University of Split School of Medicine, Split, Croatia — ORCID: 0000-0002-4878-8146
• Tina Tičinović Kurir — University of Split School of Medicine, Split, Croatia — ORCID: 0000-0001-5975-5393
• Marko Kumrić — University of Split School of Medicine, Split, Croatia — ORCID: 0000-0002-9696-3359
• Andrija Matetić — University Hospital Centre Split, Split, Croatia — ORCID: 0000-0001-9272-6906
• Joško Božić — University of Split School of Medicine, Split, Croatia — ORCID: 0000-0003-2649-0936

Abstract

**Introduction**: Previous studies showed an increased likelihood and risk of acute myocardial infarction (AMI) and hospitalizations for cardiovascular events among patients exposed to chronic use of proton pump inhibitors (PPIs). (1-3) In this study we aimed to compare parameters reflecting disease burden and cardiometabolic profile among patients treated for AMI with respect to the chronic exposure to PPIs. **Patients and Methods**: Data of 143 adult consecutive patients hospitalized for ST-elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI) during the 2019-2020 period were analyzed. All continuous variables had a normal distribution. **Results**: The mean age was 64.8 ± 11.3 years and 79.7% were men. Two-thirds (65.7%) of patients had STEMI while 34.3% had NSTEMI. The mean GRACE score in the whole cohort was 117 ± 26 points while 12.6% of patients were at high risk of in-hospital death, after adjustment for the ACS type. A total of 19 IPP+ patients were identified. Patients in the IPP+ group were significantly older and had a higher prevalence of NSTEMI compared to IPP- group while both groups did not significantly differ in terms of sex, body mass index, waist-to-hip ratio, the mean number of diseased vessels at angiography, and left ventricular ejection fraction. Patient IPP+ group had a significantly higher high-sensitivity cardiac troponin I rise from 1st to 2nd measurement compared to IPP- group (4726 ± 5938 vs. 2554 ± 3480 ng/L, p=0.025, **Table 1**). Furthermore, C-reactive protein, blood glucose, and serum creatinine levels at admission were significantly higher in IPP+ vs. the IPP- group. Finally, patients in the IPP+ group had a significantly higher risk of in-hospital and 6-month post-discharge death compared to IPP- group, as adjudicated by the GRACE score (132 ± 23 vs. 114 ± 26 points, p=0.008). ### TABLE 1: Comparison of consecutive patients with acute myocardial infarction exposed to chronic inhibitor of proton pump (IPP) use (IPP+ group) with those not exposed (IPP-group). | **Variable** | **IPP+ group (N=19)** | **IPP- group (N=124)** | **p-value** | | --- | --- | --- | --- | | Age, *years* | 71.9 ± 9.6 | 63.3 ± 11.2 | 0.003* | | Body mass index, *kg/m2* | 26.2 ± 1.7 | 27.3 ± 3.4 | 0.201 | | Waist-to-hip ratio | 1.03 ± 0.07 | 1.12 ± 0.88 | 0.644 | | Male sex | 64.7% | 81.9% | 0.100 | | NSTEMI as a type of ACS | 47.4% | 33.1% | 0.224 | | Mean Killip class | 1.11 ± 0.33 | 1.10 ± 0.40 | 0.890 | | Mean number of diseased vessels | 1.20 ± 0.44 | 1.17 ± 0.50 | 0.823 | | Left ventricular ejection fraction, *%* | 50.8 ± 12.7 | 52.1 ± 9.8 | 0.656 | | Δcardiac Troponin I value, *ng/L¶* | 4726 ± 5938 | 2554 ± 3480 | 0.025* | | C-reactive protein, *mg/L* | 27.4 ± 48.5 | 11.7 ± 20.0 | 0.015* | | Glucose, *mmol/L* | 9.5 ± 4.8 | 7.7 ± 3.0 | 0.037* | | Creatinine, μmol*/L* | 110 ± 56 | 89 ± 26 | 0.012* | | Sodium, *mmol/L* | 138 ± 2.9 | 137 ± 3.0 | 0.146 | | Potassium, *mmol/L* | 4.04 ± 0.43 | 4.08 ± 0.40 | 0.724 | | GRACE score, *points* | 132 ± 23 | 114 ± 26 | 0.008* | [†] ACS-acute coronary syndrome; AMI-acute myocardial infarction; GRACE-Global Registry of Acute Coronary Events; NSTEMI-Non-ST-segment elevation myocardial infarction. *result significant at a two-tailed p-value st to 2nd measurement **Conclusions**: Our study showed that AMI patients with chronic exposure to IPPs are older, mostly male, and tend to present with NSTEMI. These patients exhibit a larger magnitude of myocardial injury and systemic inflammation accompanied by worse renal function, and also seem to be at an increased risk of poor in-hospital and post-discharge outcomes. However, potential confounding of underlying comorbidities and age must be taken into account when interpreting these results.

Keywords

acute coronary syndrome, acute myocardial infarction, IPP, proton pump inhibitors, outcomes

DOI

Literature

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3. Casula M, Scotti L, Galimberti F, Mozzanica F, Tragni E, Corrao G, et al. Use of proton pump inhibitors and risk of ischemic events in the general population. Atherosclerosis. 2018 October;277:123–9. https://doi.org/10.1016/j.atherosclerosis.2018.08.035