Introduction
Eosinophilic esophagitis (EoE) is a chronic, allergic inflammatory disease of the esophagus. Major adverse cardiovascular events (MACE) have been associated with diseases of chronic inflammation. Data on MACE from large population-based cohorts of biopsy-proven EoE are lacking.
Aims & Methods
The aim of this study was to investigate the association between EoE and MACE. It included all Swedish adults with EoE (1990-2017) without a record of previous cardiovascular disease (CVD) (n=1,546, with follow-up until 2019). EoE was defined from prospectively recorded esophageal histopathology reports from all Swedish pathology departments (n=28) in the Epidemiology Strengthened by Histopathology Reports in Sweden (ESPRESSO) cohort. Individuals with EoE were matched with up to five general population reference individuals (n=7,281) for age, sex, calendar year and county without EoE or CVD. Multivariable-adjusted hazard ratios (aHRs) for MACEs (any of ischemic heart disease, congestive heart failure, stroke and cardiovascular mortality) were calculated using Cox proportional hazards models. In secondary analyses, individuals with EoE were compared to their siblings to account for residual confounding.
Results
The majority of individuals with EoE were male (75%), and the median age at EoE diagnosis was 37 years (IQR 19-51). Over a median of 6.0 (IQR 4.6-8.0) years of follow-up, 65 (4.2%) MACE events were observed in patients with EoE and 225 (3.1%) in reference individuals, corresponding to 6.4 vs. 4.7 events per 1,000 person-years (incidence rate difference: 1.7, 95%CI=0.0-3.4), respectively. No significantly higher overall risk (aHR=1.14, 95%CI=0.86-1.51) of MACE outcomes. No significant differences between age, sex and follow-up time were observed. When adjusting for relevant CVD medication and sibling comparison, results were similar.
| Table 1 Incidence Rates, Absolute Rate Differences and Hazard Ratios for incident Major Adverse Cardiovascular Events in patients with Eosinophilic Esophagitis compared to general population reference individuals 1990-2019 |
|
| Reference individuals | EoE |
| | | N=7 281 | N=1 546 |
| | MACE outcomes* | | |
| | Incident events (%) | 226 | 65 |
| | Incidence rate per 1000 py (95%CI) | 4.7 (4.1-5.4) | 6.4 (4.9-8.1) |
| | Absolute rate difference per 1000 py (95%CI) | 0 (ref.) | 1.7 (0-3.4) |
| | Unadjusted HR# (95%CI) | 1 (ref.) | 1.37 (1.04-1.80) |
| | Adjusted HR (95%CI) | 1 (ref.) | 1.14 (0.86-1.51) |
| | | | |
CI, confidence interval; EoE, eosinophilic esophagitis; HR, hazard ratio; MACE, major adverse cardiovascular events; py, person-years
*Includes ischemic heart disease, congestive heart failure, stroke and cardiovascular mortality.
#Adjusted for age, sex, calendar year, county of residence at index date, country of birth (Nordic country or other), educational level (compulsory school, upper secondary school or college/university), ≥1 metabolic disease (diabetes, obesity, hypertension or dyslipidemia), chronic kidney disease, atopic dermatitis, celiac disease and chronic respiratory disease (chronic obstructive pulmonary disease or asthma) diagnosis.
Conclusion
Individuals with biopsy-proven EoE had no increased risk of MACE outcomes compared to general population or sibling comparators. The absence of any association with MACEs in our study may be reassuring for patients with EoE.
Disclosure
Dr. Forss has served as a speaker and advisory board member for Janssen corporation. Dr. Uchida is a medical advisor for Sanofi-Regeneron and AstraZeneca. Dr. Roelstraete has no conflicts of interest. Dr. Ebrahimi has served as advisory board member for Boehringer Ingelheim. Dr. Garber do not have any conflicts of interest to declare related to this study. Dr. Sundström reports stock ownership in Anagram kommunikation AB and Symptoms Europe AB outside the submitted work. JFL has coordinated an unrelated study on behalf of the Swedish IBD quality register (SWIBREG). This study received funding from Janssen corporation. JFL has also received financial support from MSD to develop a paper reviewing national healthcare registers in China, and has ongoing discussions with Takeda about a celiac disease project.