WHITE RIVER JUNCTION, VT — Previous studies have established an association between laboratory-confirmed influenza infection (LCI) and hospitalization for acute myocardial infarction (AMI).
That research failed to demonstrate causality, however. In response, a study published by PLoS One added biological mediators to an established study design in an effort to elucidate the underlying mechanisms.1
Researchers from the White River Junction, VT, VAMC and international colleagues used data on biomarkers for a self-controlled case-series design. The goal was to better understand how flu infection affected hospitalization for AMI among VHA patients.
Included were veterans age 65 years and older with LCI between 2010 through 2015. Laboratory results, hospitalizations and baseline patient characteristics were pulled from VA data, with “risk interval” defined as the first seven days after specimen collection and the “control interval” as one year before and one year after the risk interval.
The examination of the role of abnormal white blood cell (WBC) and platelet count in the relationship between LCI and AMI helped explore the thrombogenic nature of the association and risk for mortality, which the authors said was key to the study.
Researchers identified 391 hospitalizations for AMI that occurred within +/-1 year of a positive influenza test. Of those, 31 (31.1 admissions/week) occurred during the risk interval and 360 (3.5/per week) during the control interval, leading to an incidence ratio (IR) for AMI admission of 8.89 (95% confidence interval [CI]: 6.16-12.84).
The study pointed out that, 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).
“We confirmed a significant association between LCI and AMI,” the authors wrote. “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.”
The study adds, “Among senior veterans, we found that the incidence of admissions for AMI was nine times as high during the seven days after LCI compared to that during the control interval (31.1 admissions per week vs. 3.5 admissions per week). The IR point estimates were highest for those older than 75 years, and for patients with elevated WBC and PC.”
Researchers advise that an elevated incidence ratio of acute myocardial infarction after influenza infection was observed among patients without a diagnosis of dyslipidemia, diabetes, or hypertension, or without prior hospitalization for acute myocardial infarction before the study period, ”suggesting LCI might raise more the risk of AMI among those without preconditions.”
The authors called for further analysis on confounders such as medication, diet and exercise and why a lower risk of AMI was identified in LCI patients with diagnosed CVD risk factors. “Perhaps medical management brought down their risk for AMI to a level even below that of those who have risk factors, although SCCS design is not able to adjust for time-varying confounding variables that could change between the risk and the control period,” they advised.
- Young-Xu Y, Smith J, Mahmud SM, Van Aalst R, Thommes EW, Neupane N, et al. (2020) Laboratory-confirmed influenza infection and acute myocardial infarction among United States senior veterans. PLoS ONE 15(12): e0243248. https://doi.org/10.1371/journal.pone.0243248
