Introduction: Despite evidence suggesting an association between influenza infection and increased risk of acute myocardial infarction (AMI) in the older adult population (aged 65 years or above), little is known about its near-term risks in middle-aged adults (aged 45 to 64 years). This study aims to estimate the risks of and association between severe influenza infection requiring hospitalization and subsequent AMI within 12 months in middle-aged adults.

Method: This is a retrospective case-control analysis of territorywide registry data of people aged 45 to 64 years admitting from up to 43 public hospitals in Hong Kong during a 20-year period from January 1997 to December 2017. The exposure was defined as severe influenza infection documented as the principal diagnosis using International Classification of Diseases codes and non-exposure as hospitalization for orthopedic surgery. Logistic regression was used to analyze the risk of subsequent hospitalization for AMI within 12 months following the exposure.

Results: Among 30,657 middle-aged adults with an indexed hospitalization, 8,840 (28.8%) had an influenza-associated hospitalization. 81 (0.92%) were subsequently rehospitalized with AMI within 12 months after the indexed hospitalization. Compared with the control group, the risk of subsequent hospitalization for AMI was significantly increased (odds ratio [OR]: 2.54, 95% confidence interval [CI]: 1.64-3.92, p<0.001). The association remained significant even after adjusting for potential confounders (adjusted OR: 1.81, 95% CI: 1.11-2.95, p = 0.02). Patients with a history of hypertension, but not those with diabetes mellitus, dyslipidemia or atrial fibrillation/flutter, were at increased risk (adjusted OR: 5.01, 95% CI: 2.93-8.56, p<0.001).

Conclusion: Subsequent hospitalization for AMI within 12 months following an indexed respiratory hospitalization for severe influenza increased nearly two-fold compared with the non-cardiopulmonary, non-exposure control. Recommendation of influenza vaccination extending to middle-aged adult population may be justified for the small but significant increased near-term risk of AMI.