Correspondence

Vascular Events after Acute Infection or Vaccination

N Engl J Med 2005; 352:1151-1153March 17, 2005

Article

To the Editor:

In their article about cardiovascular events after acute infections (Dec. 16 issue),1 Smeeth et al. do not discuss alternative, time-honored explanations for the occurrence of cardiovascular events within three days after acute infections. A reasonable explanation could be that fever and the accompanying tachycardia trigger such events, not to mention the procoagulant effects an acute infection can have. The hypoxemia that accompanies a respiratory (but not urinary) infection can adversely affect vulnerable tissue, not to mention have procoagulant effects.2 A less common phenomenon is a myocardial infarction masquerading as a respiratory infection. In one recent study, more than 40 percent of cases of myocardial infarction in women had the appearance of a respiratory infection.3 The widely held view about the role that inflammation plays in atherosclerosis and cardiovascular events has prevented recognition and discussion of the apparent paradox that common antiinflammatory agents, such as corticosteroids and nonsteroidal antiinflammatory drugs (with the exception of aspirin), may actually increase, rather than decrease, adverse cardiovascular outcomes.4,5

Michael Bursztyn, M.D.
Hadassah University Hospital, Mount Scopus, Jerusalem 91240, Israel
bursz@cc.huji.ac.il

5 References

1
Smeeth L, Thomas SL, Hall AJ, Hubbard R, Farrington P, Vallance P. Risk of myocardial infarction and stroke after acute infection or vaccination. N Engl J Med 2004;351:2611-2618
Full Text | Web of Science | Medline

2
Stone PH. Triggering myocardial infarction. N Engl J Med 2004;351:1716-1718
Full Text | Web of Science | Medline

3
McSweeney JC, Cody M, O'Sullivan P, Elberson K, Moser DK, Garvin BJ. Women's early warning symptoms of acute myocardial infarction. Circulation 2003;108:2619-2623
CrossRef | Web of Science | Medline

4
Petri M. Detection of coronary artery disease and the role of traditional risk factors in the Hopkins Lupus Cohort. Lupus 2000;9:170-175
CrossRef | Web of Science | Medline

5
Public Health Advisory: non-steroidal anti-inflammatory drug products (NSAIDS). Washington, D.C.: Food and Drug Administration, December 23, 2004. (Accessed February 24, 2005, at http://www.fda.gov/cder/drug/advisory/nsaids.htm.)

To the Editor:

Smeeth et al. found that persons with acute infections have an increased risk of cardiovascular and cerebrovascular events, whereas those who have been vaccinated do not. They conclude that this “lends strong support to the concept that systemic inflammation itself alters the probability of the occurrence of a vascular event.” We believe that this conclusion based on their data is flawed. Not discussed is the influence of acute infection on stress and on demand-induced ischemia. Acute infections, particularly those of the respiratory tract, may be associated with hemodynamic stresses that are not typically induced by vaccination. These hemodynamic stresses in high-risk older persons, such as those in the study by Smeeth et al., who had an increased prevalence of coronary artery disease, may account for the increased rates of myocardial events noted in the study. Although evidence for a link between inflammation and vascular events is abundant, demand-induced ischemia due to acute hemodynamic stressors of a clinically significant degree may be a more straightforward explanation of the findings of this study.

Nima Sharifi, M.D.
National Institutes of Health, Bethesda, MD 20892

Pirooz S. Mofrad, M.D.
Georgetown University Hospital, Washington, DC 20010

Author/Editor Response

Dr. Bursztyn raises the question of whether there might have been cases of misdiagnosis of myocardial infarction as respiratory infection. We did consider this important point. Our study identified an increase in the risk of myocardial infarction or stroke after a case of urinary tract infection or respiratory infection. We think it unlikely that myocardial infection was misdiagnosed as urinary tract infection or that either urinary tract infection or respiratory tract infection was misdiagnosed as stroke. Therefore, our conclusions that two different infectious processes increase the rate of cardiovascular events seem secure. As for the interesting question about associations between antiinflammatory drugs and event rates, it is unfortunate that the interpretation of the data are difficult because of confounding and the diversity of underlying disease states. Although we recognize that some drugs have detrimental effects, we are less certain than Dr. Bursztyn that, as a group, drugs that reduce inflammation are necessarily harmful in terms of cardiovascular events.

In our article, we list several possible mechanisms that might explain the association between acute infection and a short-term increase in cardiovascular risk. Drs. Sharifi and Mofrad suggest an additional one: that hemodynamic stresses may have played a part in mediating the effect. We agree with the correspondents that infection and systemic inflammation increase the heart rate and can alter hemodynamics and myocardial oxygen demand. Although it is conceivable that these acute changes may have contributed to the effect we observed, it seems less likely that they would have persisted during the month or so in which we found an elevated risk after infection. Furthermore, although this alternative mechanism is plausible, we do not see how this alters our conclusion that our finding “lends strong support to the concept that systemic inflammation itself alters the probability of the occurrence of a vascular event.”

Liam Smeeth, Ph.D.
Sara Thomas, Ph.D.
London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
liam.smeeth@lshtm.ac.uk

Patrick Vallance, M.D.
University College, London WC1E 6JJ, United Kingdom

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