Review
Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease: a systematic review

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Summary

Cardiac complications of influenza infection, such as myocarditis, are well recognised, but the role of influenza as a trigger of acute myocardial infarction is less clear. We did a systematic review of the evidence that influenza (including influenza-like illness and acute respiratory infection) triggers acute myocardial infarction or cardiovascular death. We examined the effectiveness of influenza vaccines at protecting against cardiac events and did a meta-analysis of data from randomised controlled trials. 42 publications describing 39 studies were identified. Many observational studies in different settings with a range of methods reported consistent associations between influenza and acute myocardial infarction. There was weaker evidence of an association with cardiovascular death. Two small randomised trials assessed the protection provided by influenza vaccine against cardiac events in people with existing cardiovascular disease. Whereas one trial found that influenza vaccination gave significant protection against cardiovascular death, the other trial was inconclusive. A pooled estimate from a random-effects model suggests a protective, though non-significant, effect (relative risk 0·51, 95% CI 0·15–1·76). We believe influenza vaccination should be encouraged wherever indicated, especially in people with existing cardiovascular disease, among whom there is often suboptimum vaccine uptake. Further evidence is needed on the effectiveness of influenza vaccines to reduce the risk of cardiac events in people without established vascular disease.

Introduction

During influenza epidemics there are many deaths and serious complications in vulnerable populations. People with underlying chronic medical disorders such as cardiovascular disease are particularly at risk.1 However, the association between influenza infection and acute myocardial infarction is unclear. Early studies reported seasonal patterns of cardiovascular deaths that were similar to patterns of influenza circulation.2, 3, 4, 5 Clinical findings in patients with influenza revealed characteristic systemic effects such as high fever, myalgia, and fatigue, but also revealed frequent myocardial involvement.6, 7, 8, 9 These findings led to the hypothesis that influenza might act as an acute inflammatory stimulus triggering cardiovascular events. Markers of systemic inflammation have been used to predict the risk of vascular disease in people,10 and inflammatory cells are an important component of atherosclerotic plaques.11 The influenza virus has extensive effects on inflammatory and coagulation pathways,12 which might lead to destabilisation of vulnerable atherosclerotic plaques and thus coronary artery occlusion—the major cause of acute myocardial infarction.13 In this systematic review, we examine the association between influenza infection and acute myocardial infarction or cardiovascular death, including the protection against cardiovascular events provided by influenza vaccines.

Section snippets

Search strategy

Searches were done using PubMed (up to February, 2009) and EmBase (from 1980 to February, 2009), without language limits. We used the following PubMed MeSH search terms: “‘influenza human’ or ‘influenza vaccines’ or ‘viruses[Majr]’ or ‘respiratory tract infections[Majr]’ and ‘myocardial infarction’”. The search was repeated with the MeSH terms “‘influenza human’ or ‘influenza vaccines’ and ‘cardiovascular diseases[Majr]’”. Keyword searches were done in both databases with combinations of the

Results

The search yielded 1869 articles, of which 99 were deemed relevant and 37 fulfilled inclusion criteria (figure 1). An additional five articles were identified by scanning reference lists of included studies and relevant reviews. 42 papers were included in our analysis, published between 1932 and 2008. Of these, 17 described ecological studies, 15 reported case–control studies, three were prospective cohort studies, two were case only studies (incorporating one self-controlled case series study

Discussion

A range of observational studies done in different settings have generally tended to support the hypothesis that acute respiratory infections—influenza in particular—can trigger acute myocardial infarction. There is also more limited evidence for an adverse effect on cardiovascular death. Two relatively small randomised trials suggest that influenza vaccination reduces the risk of cardiovascular death and some coronary ischaemic events.

This Review used a systematic, transparent search strategy,

Search strategy and selection criteria

These are described in detail in the Methods section.

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