Laboratory-confirmed influenza infection and acute myocardial infarction among United States senior Veterans

Abstract

Background Previous studies established an association between laboratory-confirmed influenza infection (LCI) and hospitalization for acute myocardial infarction (AMI) but not causality. We aimed to explore the underlying mechanisms by adding biological mediators to an established study design used by earlier studies. Methods With data on biomarkers, we used a self-controlled case-series design to evaluate the effect of LCI on hospitalization for AMI among Veterans Health Administration (VHA) patients. We included senior Veterans (age 65 years and older) with LCI between 2010 through 2015. Patient-level data from VHA electronic medical records were used to capture laboratory results, hospitalizations, and baseline patient characteristics. We defined the “risk interval” as the first 7 days after specimen collection and the “control interval” as 1 year before and 1 year after the risk interval. More importantly, using mediation analysis, we examined the role of abnormal white blood cell (WBC) and platelet count in the relationship between LCI and AMI to explore the thrombogenic nature of this association, thus potential causality. Results We identified 391 hospitalizations for AMI that occurred within +/-1 year of a positive influenza test, of which 31 (31.1 admissions/week) occurred during the risk interval and 360 (3.5/per week) during the control interval, resulting in an incidence ratio (IR) for AMI admission of 8.89 (95% confidence interval [CI]: 6.16–12.84). In stratified analyses, AMI risk was significantly elevated among patients with high WBC count (IR, 12.43; 95% CI: 6.99–22.10) and high platelet count (IR, 15.89; 95% CI: 3.59–70.41). Conclusion We confirmed a significant association between LCI and AMI. The risk was elevated among those with high WBC or platelet count, suggesting a potential role for inflammation and platelet activation in the underlying mechanism.

Podcast: Influenza-Associated Complications and the Impact of Vaccination on Public Health

“…So there are several hypotheses about these pathways, first being the inflammatory response of the body following acute infection. So direct effects of it and response can lead to an influx of inflammatory cells into a pre-existing atherosclerotic plaque in the coronary arteries, which leads to growth and destabilization or even rupture of the plaque [ 3 ]. As a second mechanism, acute infection has an effect on the body’s coagulation pathways.…”

“…As a second mechanism, acute infection has an effect on the body’s coagulation pathways. So the formation of thrombi or clots in the coronary artery is promoted through platelet activation, vasoconstriction, and endothelial dysfunction [ 2 , 3 ]. And, lastly, the balance between the metabolic demand and supply of the heart is disrupted through the infection [ 2 ].…”

Call to action: cardiologists should promote influenza vaccination

“…Several hypotheses exist that explain the ways influenza can trigger cardiovascular events, mainly through the activation of inflammatory and coagulation pathways [ 18 – 20 ]. This theory has been substantiated by a recent study, which showed that patients with elevated white blood cell and platelet counts are at higher risk of developing acute MI [ 16 ]. Influenza virus infection could lead to destabilisation of already susceptible atherosclerotic plaques, which could eventually result in coronary artery occlusion and thus acute MI.…”

“…Several other studies found an elevated risk of hospital admission for acute MI in the first 7 days after laboratory-confirmed influenza. Combining the results, the incidence ratio ranges from 6.05 to 8.89 and is highest for older adults [ 16 , 17 ]. Kwong et al.…”

Prevalence and prognostic implications of myocardial injury in patients with influenza

“…Retrospective studies, both case–control and self-controlled case-series, have demonstrated that patients who test positive for influenza are at increased risks of acute myocardial infarction (MI) and stroke. 9 , 10 , 14 , 15 Moreover, concomitant influenza was found to negatively affect the short-term prognosis of patients with MI. 16 , 17 Protection from influenza has been reported to improve prognosis in patients with MI, and a recent placebo-controlled trial showed that influenza vaccination following MI reduces future cardiovascular events.…”