Recent Respiratory Infection Doubles Risk of MI, Stroke

December 11, 2007 — A new case-control study using a large UK primary-care database has found a robust association between recent respiratory infection and major cardiovascular events [1]. The researchers found that the risks of myocardial infarction (MI) and stroke were doubled in the week following infection. "There is irrefutable evidence of a strong association between recent respiratory infection and MI and also of stroke," they report in the study, published online December 6, 2007 in the European Heart Journal.
But lead author Tim C Clayton (London School of Hygiene and Tropical Medicine, UK), stressed to heartwire: "It's important to keep this in perspective — the absolute risk for any individual is still low. Most heart attacks and strokes don't come as a result of respiratory infection. I wouldn't want people to think, 'Oh, I've got the flu so I'm going to have a heart attack.' "
Clayton and colleagues did find, however, that the association was there regardless of previous risk of cardiovascular disease, so that infections appear to confer an additional hazard on top of conventional clinical risk factors. Dr Mike Knapton (British Heart Foundation, London, UK) said: "We recommend that anyone with heart disease have the flu jab. Influenza is a serious infection, particularly in patients with heart disease, such as heart failure, and it could even trigger a heart attack."
Clayton and colleagues also suggest that trials using antiviral agents might reduce vascular events, because viruses rather than bacteria cause most respiratory infections. This might explain why several previous studies have failed to show an effect of antibiotics on cardiovascular events, they note.
A substantial number of MIs and strokes could be prevented
Clayton et al used the UK IMS Disease Analyzer Mediplus primary-care database to identify all first-time diagnoses of MI or stroke and single matched controls. Details on visits for respiratory infection over the preceding year were also extracted.
A total of 11,155 MIs and 9208 strokes were identified. For MI and stroke, respectively, there were 326 and 260 respiratory infections during the month preceding the index date. There was strong evidence of an increased risk of both events in the seven days following infection — for MI, the adjusted odds ratio (OR) was 2.10, and for stroke, the OR was 1.92. The risk was highest in the three days following infection (OR 3.75 for MI and 4.07 for stroke). The risk of events was reduced over time, so there was little excess risk beyond one month after infection.
The study has a number of strengths, say Clayton et al. First, it has been carried out in a different primary-care database — previous research linking recent respiratory infection to MI was performed using the UK General Practice Research Database (GPRD); second, there are no age restrictions; and third, the definition of respiratory infection used was likely to be more stringent than in previous studies.
This last point probably explains the fact that the observed percentages of MIs and strokes that resulted from respiratory infection were low (less than 2% of cases), they say. However "the absolute numbers of MIs and strokes that could potentially be prevented is substantial, because these are common conditions," they point out.
Associations also seen in those at high risk to begin with; infection is additional hazard
Another strength of this current study is the inclusion of extensive information on other risk factors for stroke and MI, enabling the researchers to see whether the association was seen at all levels of preceding risk.
"It is sometimes suggested that incidence in individuals who are at high risk to begin with will not significantly be affected by an additional risk factor," they say.
However, for MI, they did find significantly raised ORs associated with respiratory infection at all levels of risk, "suggesting that the mechanism(s) responsible operate at all levels of prior underlying heart attack risk."
The same "may also be true of stroke," they note, although the strength of the association "may be less at high rather than low levels of risk."
They say that two further research approaches will show whether the association seen between recent respiratory infection and MI/stroke is one of cause and effect.
First, work on the mechanisms through which infection might increase the incidence of major arterial events might shed some light on the issue, they say. And second, intervention studies using antiviral agents, which can reduce the duration and severity of established influenza, for example, should yield further insight, they conclude.
The British Heart Foundation funded the study. The study authors have disclosed no relevant financial relationships.
Source
Clayton TC, Thompson M, Meade TW. Recent respiratory infection and risk of cardiovascular disease: case-control study through a general practice database. Eur Heart J. 2007:doi:10.1093/eurheartj/ehm516.