Respiratory Infections as Predictors of Hospital Admission for Myocardial Infarction and Stroke: Pathophysiologic and Therapeutic Considerations

To the Editor—We read with interest the study of Blackburn et al [1], in which respiratory infections caused by influenza, parainfluenza, rhinovirus, respiratory syncytial virus, adenovirus, or human metapneumovirus were predictors of hospital admission for myocardial infarction and stroke, in particular among those aged ≥75 years but not in people aged <65 years. The authors attributed this association to proinflammatory cytokines, thrombotic events, disruption of atherosclerotic plaques, physiological impacts on heart rate, vasoconstriction, and perhaps comorbidities. They suggested evaluation of the impact of vaccination, antivirals, and antithrombotic agents. However, in a recent study [2], the acute myocardial infarction incidence was found to be 6 times higher in the 7-day interval after laboratory confirmation of influenza in unvaccinated patients and, surprisingly, in vaccinated patients. Endothelial dysfunction, thrombogenic diathesis, increased metabolic demand, hypoxemia, hypotension, and occlusive thrombus stress on the vascular system were reported as possible causes. Furthermore, influenza and other acute respiratory infections have been found [3] to constitute triggers for out-of-hospital cardiac arrest. Extreme influenza epidemics were associated with higher risk of out-of-hospital cardiac arrest. The authors of this study suggested that several weeks’ prevention for extreme influenza infections should be implemented. Indeed, there is evidence that the heart and other organs are affected by influenza virus transmission to extrarespiratory tissues inducing proinflammatory cytokine responses such as interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-a), and interleukin 8 (IL-8) that are implicated in pathogenesis of myocardial infarction [4]. High circulating concentrations of IL-6 have been correlated with increased risk of coronary events, and the IL-6 receptor could provide a novel therapeutic approach to prevention of coronary artery disease [5]. Males with elevated TNF-α levels present a 70% increase of myocardial infarction risk compared with the respective lowest TNF-α quartile [6]. Interestingly, high levels of IL-8 in ST segment elevation myocardial infarction complicated with heart failure have been associated with less improvement, namely worse prognosis [7]. Therefore, cytokines could emerge as potential therapeutic targets for influenza, with significant impact on concomitant myocardial infarction and out-of-hospital cardiac arrest. Because the underlying pathophysiology of these associations is multifactorial and involves complex interactions, future studies should be considered using more precise modeling methods.