A Shot in Arm, a Boost for the Heart: Flu Vaccination Reduces AMI Risk

August 26, 2013

SYDNEY, Australia — More data, this time a case-control study of individuals hospitalized in Australia, suggests that vaccination against the influenza virus reduces the risk of ischemic events[1]. The influenza virus, on the other hand, was not a significant predictor of acute MI (AMI), report investigators.

"Influenza vaccination in the study year was significantly protective against AMI, with unvaccinated subjects almost twice as likely as vaccinated subjects to have AMI," report Dr Raina MacIntyre (University of New South Wales, Sydney, Australia) and colleagues in their study, published online August 22, 2013 in Heart. "Our finding of vaccination being a protective factor is validated by the fact that other significant predictors of AMI in the model (age, gender, smoking, high cholesterol) are accepted risk factors for AMI."

The study also showed that recent influenza infection was a common comorbidity in patients with ischemic disease, with 9.5% of the study participants recently having had the flu. This finding suggests that a "clinical diagnosis of influenza may be missed in hospital patients with other presentations," say investigators.

More Fuel to the Fire

Previous epidemiological studies have suggested that influenza is associated with an increased risk of all-cause mortality and cardiovascular hospitalizations. These studies have also shown a spike in the rates of hospitalization for AMI and mortality during the flu season. However, some recent studies, including those reported by heartwire , have shown that vaccination against the flu could reduce the risk of MI.

In one analysis of the data, researchers found that vaccination for influenza likely protected against MI in people with preexisting cardiovascular disease, but more research was needed to establish whether vaccines helped prevent MI in people without vascular disease. Another case-control study suggested that vaccination against influenza could cut the risk of MI by 20%.

In 2012 at the Canadian Cardiovascular Congress, Dr Jacob Udell (University of Toronto, Ontario) presented the results of a meta-analysis of four studies involving 3227 patients, about half of whom had no established cardiovascular disease and half with stable cardiovascular disease or acute coronary syndrome. Like the other studies, Udell reported that vaccination against the flu reduced the risk of major adverse cardiovascular events by 48%.

Udell, who was not involved in the Australian study, said that despite the lack of a gold-standard randomized, clinical trial proving the benefits of flu vaccination on cardiovascular end points, he is a proponent of vaccination. "I'm 110% supportive of the idea," he told heartwire . "And I don't think it's for a lack of evidence at this point or a lack of effort on anyone's part. I think the overarching reason when people are surveyed is either a disbelief in the benefit or a concern that the short-term adverse effects, such as a sore arm or they get the flu, trump any benefit."

If it is a question of efficacy for the nonbelievers, the time is ripe for a significantly powered large-scale randomized trial to answer the question, he added.

Risk of AMI Reduced 45% With Vaccination

In the latest Australian paper, MacIntyre and colleagues investigated whether influenza was a significant and unrecognized illness preceding AMI. There were 275 patients with AMI and 284 patients without AMI included in the case-control study, and just over half of all patients were vaccinated in the year they were recruited for the study. Of the 559 participants, 12.4% of the cases and 6.7% of the controls had influenza, a near twofold difference in risk (odds ratio 1.97; 95% CI 1.09–3.54).

Multivariate Logistic Regression Predictors of AMI

Variable Odds ratio (95% CI)
Evidence of recent flu infection 1.07 (0.53–2.19)
Age* 0.96 (0.94–0.97)
Sex (male) 3.83 (.54–5.78)
Self-reported high cholesterol 2.00 (1.35–2.97)
Current smoker 2.11 (1.25–3.56)
Flu vaccination in study year 0.55 (0.35–0.85)

*Age as a continuous variable

To heartwire , Udell said one of the intriguing findings of the case-control study was the result from the multivariate analysis. After adjustment for confounding variables, including age, male sex, high cholesterol levels, current smoker status, and influenza vaccination in the study year, influenza exposure was not associated with a risk of AMI despite an association observed in univariate analysis. In the multivariate analysis, flu vaccination was associated with a 45% reduction in the risk of AMI, but recent flu exposure was not.

"This means one of two things," Udell told heartwire . "That the vaccine is protective, or that the vaccine is having some effect that has nothing to do with influenza, maybe some immune-activation benefit. It's all very hypothesis-generating and provocative at this point and needs to be validated in a large-scale multicenter clinical trial."

Udell said the accumulating data supporting the cardiovascular benefit of flu vaccination have outpaced the mechanistic explanations. In the case of the protection against AMI and major adverse cardiovascular events, including stroke, the results are so intriguing that researchers "almost have to go back to the drawing board to reevaluate the triggers of destabilization in these patients." The present study also highlights how few people are vaccinated against the flu. Despite all the evidence suggesting a cardiovascular benefit to vaccination, in addition to protecting against the flu, just half of the population receives the influenza vaccine, he noted.

The study was funded by a research grant from GlaxoSmithKline. MacIntyre reports grant support from GlaxoSmithKline, CSL, Sanofi Pasteur, Merck, and Pfizer. Disclosures for the coauthors are listed in the paper. Udell reports no conflicts of interest.

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