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Influenza-Associated Heart Attacks

By Amesh A. Adalja, MD, June 3, 2011

While the majority of deaths from influenza are caused by pneumonia and ensuing respiratory failure, influenza can also trigger many other potentially fatal conditions, among them, rhabdomyolysis, myocarditis, Guillain-Barré syndrome, and Reye’s syndrome. There has also been some evidence to link myocardial infarction (MI) to influenza;1 however, because both flu and MIs peak in the same months (December to March), it has been difficult to disentangle the shared seasonality and establish a definitive relationship.

That relationship is postulated to exist because of the systemic inflammation that occurs with influenza. Warren-Gash and colleagues attempted to clarify this relationship by conducting a time series analysis of MI and influenza rates in Hong Kong, England, and Wales (in Hong Kong, influenza displays less seasonality than in temperate climates). Their results, just published in the Journal of Infectious Diseases,2 suggest that there is a relationship between influenza infections and subsequent MIs.

Strong Associations Found with MI-associated Deaths and Hospitalizations

The researchers analyzed 10 years of data (1999-2008) on MI hospitalizations and deaths in all locations; data were aggregated by influenza surveillance week. Influenza data from the same period included influenza-like illness (ILI) visits to primary care physicians (PCPs) and rate of positivity on influenza nasal/throat swabs. Temperature and humidity parameters were also incorporated. Hong Kong data from 2003 were not included due to the SARS outbreak at that time.2

In England and Wales, PCP visits for ILI were strongly associated with MI-related deaths. In Hong Kong, a similar association was found between MI-related deaths and the proportion of clinical specimens positive for influenza. MI-related hospitalizations were also associated with ILI visits in England and Wales; in Hong Kong, associations were seen using the proportion of positive clinical samples. The effects were not exactly synchronous, and the highest associations sometimes lagged by up to 3 weeks. Associations were strongest for those over 60 years of age.2

Proportion of MIs Associated with Influenza

In England and Wales, approximately 3% of MI-associated deaths and 1% of hospitalizations for MI could be attributed to influenza. In Hong Kong 3.9% to 5.6% of MI deaths and approximately 3% of MI hospitalizations were attributed to influenza. When influenza circulation reached very high levels (90th percentile and above), the proportion of deaths (as well as hospitalizations) from MIs accordingly increased to up to 13.6% in Hong Kong and 11.8% in England and Wales.2

Influenza-associated MIs
England/
Wales
Hong Kong
MI Hospitalizations1%3%
MI Deaths3%3.9-5.6%
MI Deaths (90th percentile of flu activity)11.8%13.6%

Implications for Vaccination and Antiviral Therapy

This study has several limitations but nonetheless provides more evidence to link influenza and MI. One major limitation was the exclusion of other respiratory viruses that also cause ILI and the same systemic inflammation triggered by influenza. Another limitation is the identified lag times; had the researchers been able to account more precisely for the time courses of MI and influenza, the results would have been stronger.2 Nonetheless, this study’s findings, coupled with those from earlier studies with similar results,3 should inform vaccination and antiviral policies. Those patients at high risk for MI because of family history, prior coronary artery disease, tobacco use, or diabetes mellitus should be priority groups for influenza vaccination, and the threshold for instituting antiviral treatment in this cohort should be relatively low. In fact, a military study published in 20094 revealed a significant decrease in recurrent cardiovascular events in those with prior cardiovascular disease who received oseltamivir compared to those who did not.

Clearly, future pandemic planning will have to account for an expanded notion of people who are at risk for influenza-related comorbidities, including such noninfectious complications as MIs.

References

  1. Madjid M, Miller CC, Zarubaev VV, et al. Influenza epidemics and acute respiratory disease activity are associated with a surge in autopsy-confirmed coronary heart disease death: results from 8 years of autopsies in 34,892 subjects. Eur Heart J 2007; 28:1025-10.
  2. Warren-Gash C, Bhaskaran K, Hayward A, et al. Circulating influenza virus, climatic factors, and acute myocardial infarction: a time series study in England and Wales and Hong Kong. J Infect Dis 2011 Jun 15;203(12):1710-7.
  3. Finelli L, Chaves SS. Influenza and acute myocardial infarction. (Commentary) J Infect Dis 2011 Jun 15;203(12):1701-4.
  4. Casscells SW, Granger E, Kreiss AM, et al. Use of oseltamivir after influenza infection as associated with reduced incidence of recurrent adverse cardiovascular outcomes among military health system beneficiaries with prior cardiovascular diseases. Circ Cardiovasc Qual Outcomes 2009; 2: 108-115. http://circoutcomes.ahajournals.org/content/2/2/108.abstract. Accessed June 2, 20011.