Investigating Infection-Related Hospitalization as a Risk Factor for Incident Heart Failure and Mortality among Heart Failure Patients

Abstract

HF is a growing epidemic with an estimated prevalence of 6.5 million individuals in the U.S., and poor outcomes persist despite recent therapeutic advancements. Studies have shown that an inflammatory response to infections may become dysregulated, thereby promoting collateral myocardial damage that may result in HF. Infection is also a common cause of hospitalization among HF patients and may lead to poor prognosis and high mortality. Limited data exist examining the relationship between infection-related hospitalization (IRH) and HF along with HF subtypes, HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). Further, few studies have explored mortality rates following an IRH in HF patients or whether certain types of IRH are stronger predictors of mortality. This dissertation leveraged the strengths of large claims data (MarketScan) and a community-based study (ARIC) to address these limitations and parse out the dynamic relationship between infection-related hospitalization and HF with several manuscripts. The first manuscript, a case-crossover study of beneficiaries in the MarketScan databases, assessed the association between IRH and incident HF. IRH was associated with incident HF after both 1- and 3-months. The second manuscript investigated the association between IRH and long-term incident HF in the Atherosclerosis Risk in Communities study (ARIC). IRH was associated with a two-fold greater risk of incident HF, HFrEF, and HFpEF. Findings were stronger among those with HFpEF, for which treatment options are limited. Results from the first manuscript aligned with those of the second manuscript and both found respiratory, pneumonia, and blood/circulatory infections to have the strongest associations with incident HF. The third manuscript explored the relationship between IRH and mortality among HF patients in ARIC. IRH was associated with a two-fold greater risk of mortality among those with HFpEF, HFrEF, or unclassified HF. Respiratory, pneumonia, and other infections had the strongest associations with mortality. Our findings support prior literature linking IRH to HF risk and increased mortality among HF patients. These findings may have significant population-level implications given the high prevalence of IRH and the burden of HF on our aging society. Aim 1: Investigate the association between infection-related hospitalization and incident HF using U.S.-based claims data from MarketScan. Aim 2: Investigate the association between infection-related hospitalization and incident HF and HF subtypes (HFrEF or HFpEF) using a longitudinal community-based cohort study, ARIC. Aim 3: Among HF (HFrEF and HFpEF) patients, investigate the association between infection-related hospitalization and mortality using a longitudinal community-based cohort study, ARIC.