A 5% Absolute Increase in Influenza Activity Associated with a 24% Increase in Heart Failure Hospitalizations, According to New Study The Atherosclerosis Risk in Communities Study

A study conducted by Sonja Kytömaa and Sheila Hegde of the cardiovascular division, Brigham and Women’s Hospital, Boston, Massachusetts, reported that influenza activity was temporally associated with an increase in HF hospitalizations across 4 influenza seasons. According to the publication in JAMA Cardiology, these data suggested that influenza could contribute to the risk of HF hospitalization in the general population.

While several previous studies examining the association between influenza and CV disease had focused on mortality, fewer had explored the extent to which influenza contributed to CV hospitalizations specifically due to heart failure (HF). Patients with or at risk for HF were thought to be especially vulnerable to influenza-associated complications because of some degree of immunocompromise and had been shown to mount less vigorous responses to influenza vaccines. In order to address the temporal association between influenza activity and hospitalizations, especially those caused by heart failure (HF),  investigators used data from the community surveillance component of the ARIC (Atherosclerosis Risk in Communities) study, a population-based study with hospitalizations sampled from four US communities, and data collected from 451,588 adults aged 35-84 years residing in the ARIC communities from annual cross-sectional stratified random samples of hospitalizations during October 2010 to September 2014. They hypothesized that increased influenza activity would be associated with an increase in hospitalizations for HF and MI among adults in the community.

Monthly influenza activity, defined as the percentage of patient visits to sentinel clinicians for influenza-like illness by state, as reported by the Centers for Disease Control and Prevention Surveillance Network were obtained. The primary outcome was the monthly frequency of MI hospitalizations (n = 3,541) and HF hospitalizations (n = 4,321), collected through community surveillance and adjudicated as part of the ARIC study. The investigators used a Poisson regression model to associate monthly influenza activity with hospitalizations for MI and HF. In the period between October 2010 and September 2014, 2,042 (47.3%) and 1,599 (45.1%) of the sampled patients who were hospitalized for HF and MI, respectively, were women and 2,391 (53.3%) and 2,013 (57.4%) were white, respectively. Sonja Kytömaa and his colleagues noted that a 5% monthly absolute increase in influenza activity was associated with a 24% increase in HF hospitalization rates, standardized to the total population in each community, within the same month after adjusting for region, season, race/ethnicity, sex, age, and number of MI/HF hospitalizations from the month before (incidence rate ratio, 1.24; 95% confidence interval [CI], 1.11-1.38; p < 0.001), while overall influenza activity was not significantly associated with MI hospitalizations (incidence rate ratio, 1.02; 95% CI, 0.90-1.17; p = 0.72). Influenza activity in the months before hospitalization was not associated with either outcome. Thus, the model suggested that in a month with high influenza activity, approximately 19% of HF hospitalizations (95% CI, 10-28%) could be attributable to influenza.

Speaking of the underlying mechanisms, investigators stated that the exact mechanism by which influenza infection led to an increased risk for acute CV events was not understood, but several mechanisms were likely to contribute. “Influenza increases metabolic demand and, in the setting of hypoxemia, may exacerbate underlying cardiac conditions. Patients with HF have limited cardiac and respiratory reserves and are unlikely to tolerate infection-associated cardiac compromise. Infection associated upregulated sympathetic nervous system activity may worsen HF, and infection concurrent with renal dysfunction may lead to volume overload. Proinflammatory cytokine level elevations during infection may precipitate plaque rupture and be associated with myocardial depression. Histologic findings from cardiac tissue samples from autopsies following deaths due to influenza have supported findings of acute myocarditis and myocyte necrosis,” they added. Lastly, several limitations of this analysis were to be noted. The individual influenza illness or vaccination status of those hospitalized for HF or MI was not known; therefore, the authors could not make inferences at an individual patient level regarding influenza infection and subsequent CV events. Similarly, while they associated population-level ILI activity with events, it was possible that other infectious causes that could parallel influenza activity may have accounted for some of the association. It was also possible that another infectious cause accounted for the high MI/HF rates observed during the 2011 to 2012 season, which was reported as a low virulence year. The respiratory syncytial virus often cocirculated with influenza and may have been responsible for the high MI/HF rates that year. It was also possible that those admitted for severe flu with a prior history of HF may have been coded as having HF because of prior knowledge of the disease. The authors, however, drew the conclusion that influenza activity was temporally associated with an increase in HF hospitalizations across four influenza seasons. While these data suggest that influenza activity should be addressed in efforts to prevent HF hospitalizations, additional prospective studies are indicated to assess whether such strategies to reduce influenza activity at the population level will actually reduce the incidence of MI and HF hospitalizations.