Nontyphoidal salmonellosis is associated with an increased risk of stroke: Insights from multinational real-world data

Abstract

Background:

Stroke is a significant cause of morbidity and mortality worldwide, contributing substantially to the global burden of disease. In low- and middle-income countries, stroke tends to occur at younger ages, with infection being one of the notable contributing factors. Previous studies have explored the impact of nontyphoidal Salmonella (NTS) on vascular and blood-related diseases, with animal experiments confirming related mechanisms. This study aims to investigate the association between NTS and cerebrovascular diseases (CVDs), with a focus on identifying specific patient populations more susceptible to stroke due to infection.

Methods:

This retrospective cohort study utilized the TriNetX database, including 4708 patients infected with NTS compared with a healthy population, with disease risk tracked over 6 months, 1 year, and lifelong periods. The primary outcome was CVDs (ICD-10-CM: I60-I69), while secondary outcomes examined hemorrhagic stroke (ICD-10-CM: I60-I62) and ischemic stroke (ICD-10-CM: I63). Subgroup analyses were conducted based on gender and age at index, with sensitivity analysis performed by comparing hospitalized patients, utilizing different databases, and evaluating the specificity of the NTS-CVD association by examining patients with a higher risk of acute myocardial infarction (AMI).

Results:

The lifelong hazard ratios (HRs) for cerebrovascular diseases (CVD), hemorrhagic stroke, and ischemic stroke following NTS infection were 1.606 (95% confidence interval (CI), 1.410–1.830), 1.866 (95% CI, 1.304–2.669), and 1.717 (95% CI, 1.385–2.130), respectively. A significant increase in the risk of hemorrhagic stroke was observed in the short term and mid-term, with HRs of 3.345 (95% CI, 1.091–10.259) and 2.816 (95% CI, 1.184–6.699), respectively. Subgroup analyses indicated statistically significant associations with the primary outcomes across all age groups. Males demonstrated a higher risk of hemorrhagic stroke, with an HR of 1.891 (95% CI, 1.142–3.310), whereas females exhibited a stronger association with ischemic stroke, with an HR of 1.592 (95% CI, 1.189–2.132). These associations remained significant among hospitalized patients, while no significant relationship was observed between NTS infection and AMI. The findings of this study were reproducible in a US-based database.

Conclusion:

There is a significant association between NTS and CVD, with a particularly important impact on the occurrence of stroke in younger populations, especially regarding the elevated risk of hemorrhagic stroke.