Acute Respiratory Tract Infections and AMI: There May Be a Connection

ABSTRACT & COMMENTARY

Synopsis: In a large case-control analysis, the risk of acute myocardial infarction was 2-3 times higher in patients who had acute respiratory tract infections within two weeks of the event.

Source: Meier CR, et al. Lancet 1998;351:1467-1471.

The role of acute and chronic infections, especially of the respiratory tract, and the pathogenesis of coronary artery disease and arterial sclerosis is gaining increasing attention. It appears that both recurrence and death from acute myocardial infarction (AMI) occurs more often in winter months, when respiratory tract infections are more common. Previous data have suggested that influenza mortality, especially in the elderly, is often the result of increased myocardial infarction.1 Similar results have also suggested increased cardiovascular death following pneumonia. In fact, recent randomized control trials of macrolide antibiotics suggested that myocardial infarction may, in fact, be reduced when these agents are used prophylactically.2,3 Chlamydia pneumoniae infection has been associated with accelerated atherosclerosis.

Now, more data from a large case-control analysis, using the general practice research database of the United Kingdom, suggests a further association. Patients under age 75, without other clinical risk factors for AMI and with a first-time diagnosis over a two-year period were studied. Cases were matched to four controls based on age, sex, and the practice attended. There were 1922 cases and 7649 controls.

A case-crossover design was used to study the effect of brief and transient exposure on the risk of an acute outcome, such as AMI. Patients identified with AMI were predominately male (approximately 75%) and between ages 60 and 75 (approximately 61%). Diagnosis of first AMI was identified using documented diagnostic criteria including chest pain, electrocardiographic, enzymatic, treatment criteria (fibrinolysis), or angiographic documentation of recent infarction. Compared to 0.9% of controls, 2.8% of cases had an acute respiratory-tract infection that led to a physician visit within the 10 days prior to AMI.

The odds ratio for AMI, in such patients, was 3.0. Beyond 11 days, there was no substantial increased risk for AMI in patients who had a respiratory-tract infection. Current smoking and body-mass index of greater than 30.0 kg/m2 were independent risk factors for AMI. There was no increased risk of myocardial infarction in relation to acute urinary tract infection.

COMMENT BY ALAN M. FEIN, MD

It is clear that pneumonia, especially when severe, increases mortality in relation to its effects on other organs, with significant morbidity and mortality resulting from AMI, increased rates of heart failure, stroke, and diabetic crisis. However, the data presented by Meier et al offer a more subtle association.

In this large study of 9000 patients, an acute respiratory-tract infection was identified as a risk factor for AMI. This risk was three times higher than those who had an acute respiratory tract infection in the 10 days prior to cardiac presentation. After about two weeks, this association waned. While the authors point out that they could not independently validate the diagnosis of respiratory tract infection, these data do add to a growing body of literature supporting this association.

Possible pathophysiologic explanations offered included increased systemic inflammation with increased C-reactive protein leading to leucocytosis and alterations in endothelial function that might create instability in atheromatous plaques, rupture, and clotting. Alterations in coagulation are also possibly related to changes in fibrinogen, circulating cytokines, and endogenous vasodilators like nitric oxide. As pointed out by the authors, this adds increasing importance to prevention of respiratory tract infections through the use of influenza and pneumococcal vaccination in eligible patients (over age 65 or with comorbid medical illnesses). It also raises the specter of secondary prevention through the use of prophylactic antibiotics. Whether this phenomena represents infection, a non-specific "epi-phenomena," or reaction to specific respiratory pathogens that will have to be targeted remains to be determined.

Currently, the association between respiratory tract infection and myocardial infarction and death grows ever closer and offers another potential point of intervention. It is clear that one can never discount the importance of microorganisms in the pathogenesis of seemingly unrelated diseases.

References

    1. Tillett HE, et al. Excess deaths attributable to influenza in England and Wales: Age at death and certified cause. Int J Epidemiol 1983;12:344-352.

    2. Gurfinkel E, et al. Randomised trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS pilot study. Lancet 1997;350:404-407.

    3. Jick H, et al. Validation of information recorded on general practitioner based computerised data resource in the United Kingdom. BMJ 1991;302:766-768.