In a perfect world, the conclusions drawn from medical research would always be unequivocal and we would be able to automatically accept their results as being the final word on the subject.
But as we’ve seen often in the past (When Studies Collide & When Studies Collide (Revisited)), no research methodology is perfect, all studies are subject to limitations, and it isn’t unusual to end up with conflicting results from different research teams.
While we would all like medicine to be based on treatments, drugs, and procedures proved – beyond a shadow of a doubt – to be safe and effective . . . sometimes we must accept a lower burden of proof -the preponderance of evidence – instead.
All of which brings us to a new study out of Australia – published yesterday in the BMJ Journal Heart, that finds compelling – but not exactly conclusive – evidence that flu shots may reduce the risk of heart attacks.
If all of this sounds vaguely familiar, it’s because we’ve trod this ground before.
In 2010 we saw a study in the CMAJ: Flu Vaccinations Reduce Heart Attack Risk that found that those over the age of 40 who get a seasonal flu vaccine each year may reduce their risk of a heart attack by as much as 19%.
Almost immediately questions were raised over the way this study was conducted (see Vaccine/Heart Attack Study Questioned). The primary concern was these researchers only looked at heart attacks during `flu season’, without the control of looking at AMI risks year-round.
Last year, in Study: Influenza And Heart Attacks, we looked at a study appearing in the Journal of Infectious Diseases that suggested Influenza - and other acute respiratory infections - can act as a trigger for heart attacks. There was an accompanying editorial called Increasing Evidence That Influenza Is a Trigger for Cardiovascular Disease published in the same issue.
In February of this year, in Another Study Links Heart Attacks & Influenza, we looked at a study from the University of Iowa that appeared in the January issue of the journal of Epidemiology and Infection linking spikes in AMIs (acute myocardial infarction) to influenza during the winter months, and also finds a similar spike in AMIs during the H1N1 pandemic wave of the fall of 2009.
Today’s study, which looked 559 patients over three flu seasons in Sydney, Australia, finds a 45% reduction in AMI risk among those who had received a flu vaccine.
They also found that those who had reported a recent respiratory infection were twice as likely to have a heart attack. But the link between Influenza infection and an AMI was more tenuous.
C Raina MacIntyre, Anita E Heywood, Pramesh Kovoor, Iman Ridda, Holly Seale, Timothy Tan, Zhanhai Gao, Anthea L Katelaris, Ho Wai Derrick Siu, Vincent Lo, Richard Lindley, Dominic E Dwyer
Published Online First 21 August 2013
Background Abundant, indirect epidemiological evidence indicates that influenza contributes to all-cause mortality and cardiovascular hospitalisations with studies showing increases in acute myocardial infarction (AMI) and death during the influenza season.
Objective To investigate whether influenza is a significant and unrecognised underlying precipitant of AMI.
Design Case-control study.
Setting Tertiary referral hospital in Sydney, Australia, during 2008 to 2010.
Patients Cases were inpatients with AMI and controls were outpatients without AMI at a hospital in Sydney, Australia.
Main outcome measures Primary outcome was laboratory evidence of influenza. Secondary outcome was baseline self-reported acute respiratory tract infection.
Results Of 559 participants, 34/275 (12.4%) cases and 19/284 (6.7%) controls had influenza (OR 1.97, 95% CI 1.09 to 3.54); half were vaccinated. None were recognised as having influenza during their clinical encounter. After adjustment, influenza infection was no longer a significant predictor of recent AMI. However, influenza vaccination was significantly protective (OR 0.55, 95% CI 0.35 to 0.85), with a vaccine effectiveness of 45% (95% CI 15% to 65%).
Conclusions Recent influenza infection was an unrecognised comorbidity in almost 10% of hospital patients. Influenza did not predict AMI, but vaccination was significantly protective but underused. The potential population health impact of influenza vaccination, particularly in the age group 50–64 years, who are at risk for AMI but not targeted for vaccination, should be further explored. Our data should inform vaccination policy and cardiologists should be aware of missed opportunities to vaccinate individuals with ischaemic heart disease against influenza.
While these researchers found receiving the flu vaccine to provide statistically significant protection against a heart attack, a bit counter-intuitively, they were unable to directly link influenza to an increased risk of AMI.
While we showed a protective effect of influenza vaccination against AMI, we were unable to demonstrate a direct effect of influenza infection on AMI. This could reflect low statistical power, with laboratory-confirmed influenza being a much rarer event than vaccination, which showed significant association. Furthermore, the high vaccination rate in our participants likely reduced the risk of influenza and our ability to detect a difference between groups.
Teasing out the details of this study we have a report today in the Australian Academic & research news publication The Conversation, that includes the following reaction from other researchers.
2 August 2013, 9.04am AEST
Julie Redfern, Senior Research Fellow, Cardiovascular Division at George Institute for Global Health welcomed the finding.
“Prevention of heart attacks and cardiovascular disease is a national health priority. Improving risk factors and implementing other simple measures aimed at preventing heart attacks and reducing the burden of disease are of great importance,” said Dr Redfern, who was not involved in the study.
“The potential of this study, after further research, that found a benefit of the flu vaccination on heart disease risk is important and could be one strategy that help minimise future heart risk.”
Garry Jennings, Director and CEO, Cardiologist at Baker IDI Heart and Diabetes Institute said the researchers had made a very interesting finding.
“It is not possible to say whether the flu vaccination was protective or whether people who have flu injections have other characteristics that lower their risk of heart attack. There is some support for the latter in that flu itself did not seem to increase the risk but people who had flu vaccination had lower risk,” said Dr Jennings, who was also not involved in the study.
“As the authors point out, this is cause for further investigation, particularly as there are some theoretical links related to inflammation that might have a role in the timing of a heart attack.”
While this study delivers something less than 100% proof that flu vaccines provide some protection against heart attacks, it does add incrementally to previous studies which have found links between respiratory infections, heart attacks, and `excess winter mortality’.
And if this link is valid, it makes sense that if you reduce the incidence of influenza (vaccines are usually about 50% effective) among those with coronary artery disease, you ought to reduce their rate of heart attacks.
But whether it makes sense or not, more research will be needed to know for sure. For more on this story, you may want to read Jason Gale’s report in Bloomberg News.
By Jason Gale - Aug 21, 2013 6:30 PM ET