Cardiovascular Risks Associated with Patients Infected with Scrub Typhus: A Nationwide Cohort Study

Background Scrub typhus is an infectious disease that affects multiple organs. However, the long-term cardiovascular (CV) risk in survivors remains unknown. Method A retrospective cohort study used administrative claims data from the National Health Insurance Research Database (NHIRD) to investigate the CV risk of scrub typhus survivors from January 1, 2010, to December 31, 2015. People who had prior CV events before the diagnosis of scrub typhus were excluded. The CV outcomes of interest were acute myocardial infarction (AMI), heart failure hospitalization (HFH), hemorrhagic or ischemic stroke, new-onset atrial fibrillation (AF), aneurysm or dissection of aorta, venous thromboembolism (VTE), and CV death. Result A total of 2,269 patients with scrub typhus and without a prior CV event were identified (mean age 47.8±16.1 years, 38.0% female). The health control cohort (n=2,264) was selected to compare by the frequency matching with age, gender, and co-morbidities with patients with scrub typhus. The incidence of HFH, new-onset AF, and total events was significantly higher among patients with scrub typhus than the control cohort with an adjusted hazard ratio (aHR) of 1.97, 95% confidence interval (CI) 1.13-3.42 for HFH; 2.48, 95% CI: 1.23-5.0 for new-onset AF; 1.43, 95% CI: 1.08-1.91 for total CV events, respectively. The event rates of other outcomes were similar between the two groups. Conclusion In the cohort study, survivors of scrub typhus are at heightened risk of subsequent CV events, especially for HFH and new-onset AF. These findings serve as an important reminder to physicians regarding the significant CV risk that remains present following acute scrub typhus infection. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Chang Gung Memorial Hospital Grant (CMRPG3L0781) and Ministry of Science and Technology Grant (MoST 108-2410-H-182A-002). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was conducted in accordance with the Declaration of Helsinki and the Declaration of Taipei on ethical considerations regarding health databases by the World Medical Association. The study protocol was approved, and informed consent was exempted by the Institutional Review Board of Chang Gung Medical Foundation (IRB No: 201901517B0) as all data converted from the original NHI's claim records were anonymized and due to tight regulations of on-site analysis at HWDC. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data generated or analyzed during this study are included in this published article.