| Title: | Hospital-Treated Infectious Diseases and Polygenic Susceptibility in Relation to Heart Failure and Cardiac Remodeling: Evidence from the UK Biobank and ARIC Cohorts |
| Journal: | European Heart Journal Open |
| Published: | 21 Feb 2026 |
| DOI: | https://doi.org/10.1093/ehjopen/oeag036 |
| URL: | http://dx.doi.org/10.1093/ehjopen/oeag036 |
Publication 17687
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Abstract
Abstract Aims Infectious diseases (IDs) are increasingly recognised as precipitants of heart failure (HF). However, the impact of diverse pathogens and genetic susceptibility on HF and cardiac remodeling remains unclear. Methods and results We analysed 480,154 UK Biobank (UKB) participants and 9,816 Atherosclerosis Risk in Communities (ARIC) participants free of HF at baseline. Hospital-treated IDs were ascertained with 931 ICD-10 codes and modelled as time-varying exposures. Incident HF, HF with preserved (HFpEF) and reduced ejection fraction (HFrEF) were identified through hospital records and adjudication. Polygenic risk scores (PRSs) for ID - overall and pathway-specific for TGF-β, acute inflammation and myocardial fibrosis - were derived from genome-wide association study data. Multivariable Cox and Fine-Gray models estimated hazard ratios (HRs); cardiac structure and function were assessed by cardiac MRI in UKB and echocardiography in ARIC. Over median follow-up of 13.5 years (UKB) and 22.4 years (ARIC), any hospital-treated ID was associated with higher HF risk (UKB HR 1.54, 95% CI 1.46-1.63; ARIC HR 1.84, 1.68-2.00). Risks were similar for bacterial, viral, fungal and parasitic infections, peaked within 180 days (HR 5.88) and persisted >1 year. IDs increased both HFpEF (sub-HR 1.81) and HFrEF (2.03). Imaging revealed higher left-ventricular mass, wall thickness, mass-to-volume ratio and filling pressures, and lower ejection fraction among infected individuals. In infection-free participants, higher overall ID-PRS predicted incident HF (per-SD HR 1.07 UKB; 1.11 ARIC) and adverse cardiac remodeling, with strongest effects for TGF-β and acute-inflammation pathways. Conclusions Hospital-treated IDs and genetic predisposition to infection are independently associated with HF and adverse cardiac phenotypes. Integrating infection history and ID-PRS may enhance HF risk stratification and motivate trials targeting fibro-inflammatory pathways. </p>
6 Authors
- Jiazhen Zheng
- Shaojun Tang
- Quan Yang
- Zhen Zhou
- Zhuoni Zhang
- S W Ricky Lee
1 Application
| Application ID | Title |
|---|---|
| 97089 | Associations of physical multimorbidity patterns and heart structure with cognition and neuroimaging outcomes |
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