Severe Infections as a Novel Risk Enhancing Factor for Incident Heart Failure

ABSTRACT Background Severe infections might be a novel risk marker for incident heart failure (HF). We examined the relationship between infection-related hospitalization (IRH) and HF in a large clinical health system and assessed whether adding IRH improved predictive utility of contemporary HF risk equations. Methods We studied 80,880 adults (14,150 with an IRH, 66,730 age- and sex-matched comparators) aged ≥18 years without HF at baseline in the Rochester Epidemiology Project (REP) between 1/1/2005 – 12/31/2019. IRH was identified using select International Classification of Disease (ICD) codes from hospital discharge records. HF incidence was defined as ≥1 HF-related ICD codes. We used multivariable-adjusted Cox proportional hazards models to assess the association between IRH and incident HF. In a separate cohort of 29,219 adults aged 30-79 years without baseline CVD in the REP, we calculated Harrell’s C-statistic to assess whether IRH information improved discrimination of the PREVENT-HF equations. Results Among 80,880 adults, 53.3% were women, 85.6% were White, 95.1% were non-Hispanic, and mean (SD) age at index was 56.0 (20.0) years. Median follow-up time was 6.2 years. Among the IRH group, 2,729 had an incident HF event (2.51 per 100 person years) versus 4,854 with an incident HF event (0.98 per 100 person years) in the comparator group. After multivariable adjustment, the hazard ratio (HR) for incident HF among participants who had an IRH compared to those who did not was 1.50 (95% CI: 1.43, 1.58). This relationship was consistent across different types of infections. In a separate cohort, the addition of IRH to PREVENT-HF increased the C-statistic from 0.776 to 0.779 (change 0.003 [0.001-0.004]). The PREVENT-HF risk score underestimated the 10-year risk of HF by up to 9% among participants with an IRH. Conclusion IRH was independently associated with incident HF but provided negligible change to overall 10-year HF risk discrimination. However, among individuals with an IRH, incorporating this information meaningfully improved 10-year HF risk prediction, suggesting that severe infections may serve as a risk-enhancing factor warranting enhanced preventive measures, particularly in populations where IRH is more common. Clinical Perspective What’s New? We found that infection-related hospitalizations, obtained through electronic health records, were associated with incident heart failure. In a large clinical system in the upper Midwest, the PREVENT-HF equations, calculated from data available in electronic health records (EHR), accurately predicted 10-year HF risk overall, but may modestly under-estimate risk among individuals with a prior infection related hospitalization. Incorporating EHR-derived information on a broad range of previous infection-related hospitalizations may support enhanced preventive measures as a risk-enhancing factor. Clinical Implications Infection-related hospitalization (IRH) identifies adults at higher risk for developing heart failure, suggesting that severe infection events could be viewed as risk-ehnacing factors that aid in indentifying patients who may need closer follow-up and prevention efforts. Incorporating IRH into sequential risk assessment frameworks beginning with the PREVENT-HF equations highlights personalized opportunities for prevention for patients recently hospitalized with infection.