Heart failure (HF) affects more than 37 million people worldwide. The prognosis after an HF diagnosis remains poor, with a five-year survival rate of less than 50%. The number of HF cases continues to increase due to the aging population. An abnormal immune response to infections can lead to damage to the heart muscle, contributing to the development of HF.
The present study, published in the Journal of the American Heart Association, aimed to explore the relationship between HF and infection-related hospitalizations (IRH) over 31 years of follow-up in the Atherosclerosis Risk in Communities (ARIC) study. This study also investigated the association of IRH (influenza, respiratory, hospital-acquired, digestive tract, blood/circulatory, skin, urinary tract, and other infections) with risk of HF subtypes such as HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF).
In this prospective population-based study, a total of 14,468 patients (mean age = 54±6 years, female = 55%, Black = 26%) without HF were recruited between 1987 and 1989 from 4 US communities (Visit 1). IRH and incidences of HF were identified according to International Classification of Diseases (ICD) codes. Multivariable adjusted Cox proportional hazards analysis was used in this method. The median follow-up time was found to be 27 years.
Results showed that 46% of patients had IRH and 25% had incident HF. The incidence rate of HF events/10000 person-years from visit 1 to 2018 was 107.6. The results of the matched analysis were slightly reduced compared to the unmatched analysis with hazard ratios (HR) of 1.62 (95% confidence interval [CI], 1.45-1.82).
In sensitivity analysis with follow-up restricted to the 25th, 50th, and 75th percentiles, the HR for incident HF in patients with versus without infection was reported as 2.5 years (HR=2.13 [95% CI, 1.72–2.64]), 6 years (HR=1.77 [95% CI, 1.52–2.05]) and 12.3 years (HR=1.62 [95% CI, 1.43–1.83]).
From unmatched Cox analysis, the incidence rate of HF was observed as 2.35 (95% CI, 2.19–2.52) in participants with IRH compared to participants without IRH. Between 2005 and 2028, the cumulative incidence of HFrEF was 4.7% (360/7669), and the incidence of HFpEF was 5% (382/7669). Additionally, incidence rates of HFrEF and HFpEF were found to be 42.2/10000 person-years and 44.8/10000 person-years, respectively. After adjusting for multiple variables, IRH was associated with both HFrEF (HR, 1.77 [95% CI, 1.35–2.32]) and HFpEF (2.97 HR, 2.97 [95% CI, 2.36–3.75]).
In the fully adjusted model, a strong association was observed between HF and infections like blood/circulatory (HR, 2.57 [95% CI, 1.62–4.09]) and respiratory infections (2.25 [95% CI, 2.05–2.48]). In contrast, a slight association was observed with digestive tract infections (HR, 1.25 [95% CI, 1.01–1.54]). Overall, the association was similar among different types of infections.    Â
This study’s limitations include baseline covariate measurement potential, unmeasured confounding, selection bias, misclassification, and missing history of infection.
In conclusion, the study findings suggest that IRH was associated with incident HF in the community-based adult population with a stronger association for HFpEF and HFrEF. These findings align with prior research linking IRH to HF risk. This highlights the need for future studies to prevent HF burden through infection prevention strategies, including vaccination. If future research confirms a causal relationship, the public health impact could be significant, given the high prevalence of infections and the growing HF burden among an aging population.
Reference: Molinsky RL, Shah A, Yuzefpolskaya M, et al. Infection-related hospitalization and incident heart failure: the Atherosclerosis Risk in Communities study. J Am Heart Assoc. 2025;14(3):e033877. doi:10.1161/JAHA.123.033877
