Influenza and Acute Myocardial Infarction — Causal Link or Spurious Association?

In this issue of NEJM Evidence, de Boer et al.1 investigate a linkage between acute myocardial infarction and influenza infection with the application of a self-controlled risk interval study, a design commonly applied to evaluate increased risk of rare side effects from vaccines.2,3 The authors studied whether acute myocardial infarction was more likely to occur within 1 week after influenza diagnosis through a comparison of the relative likelihood of two types of events: acute myocardial infarction within 7 days after a positive influenza test result and acute myocardial infarction with influenza infection occurring outside a 7-day window.1 Basically, the authors evaluated whether the sequential but nearly coincident occurrence of influenza and acute myocardial infarction was more likely than the two events occurring far apart in time.