Autopsy study supports link between flu, heart attacks

Apr 24, 2007 (CIDRAP News) – US and Russian researchers report that peak death rates from heart disease seemed to coincide with peak influenza activity in a Russian population over an 8-year period, suggesting that flu contributes to heart attacks.

The research team, led by Mohammad Madjid, MD, of the University of Texas Health Science Center in Houston, used autopsy reports in St. Petersburg, Russia, to explore the relationship between flu epidemics and cardiac deaths. Their results were published online Apr 17 by the European Heart Journal (EHJ).

"Influenza epidemics are associated with a rise in autopsy-confirmed coronary deaths," the authors write. "Influenza vaccination should be advocated for patients at high risk of developing cardiovascular events."

During the 1993 to 2000 study period, few St. Petersburg residents received flu shots or statin drugs, according to the report. "This enabled us to see what happened naturally in the absence of these medicines," said Madjid in an EHJ press release.

He said the group relied on autopsy reports because doctors often don't list influenza on the death certificate when a patient has died of a heart attack, and they sometimes miss heart attack symptoms when patients have flu or pneumonia. Another advantage of using the St Petersburg population for the study was that the area had an autopsy rate near 70%.

For the 8-year span, researchers studied weekly death rates from acute myocardial infarction (AMI) and ischemic heart disease (IHD). They compared those rates with the number of acute respiratory disease cases reported by the city's public health service and information on influenza epidemics from local surveillance agencies. Influenza A (H3N2) was the prevailing flu strain during all the study years, except the 1994-95 season, when an influenza B strain was most common.

The investigators found that 11,892 people died of AMI and 23,000 died of IHD. Most of the patients were elderly, and the women were older than the men (median ages, 75 and 65, respectively). The length of the flu epidemics averaged 2.9 months.

The data showed that peaks in AMI and IHD mortality occurred during the flu epidemics and coincided with the peak weeks for respiratory illnesses in all years except 1998, when respiratory illness activity was milder than other years.

During epidemic weeks, patients' chances of dying from AMI increased by a third, and their chance of dying from IHD increased by a tenth, Madjid said in the EHJ press release.

The authors found similar patterns when they looked at four subgroups of patients: those aged 50 and older, 70 and older, men, and women.

New findings consistent with others
Kristin Nichol, MD, MPH, an influenza vaccine researcher who is chief of medicine at the Veterans Administration Medical Center in Minneapolis, said the findings are consistent with others that have shown a correlation between seasonal flu and cardiac events. She said it was useful to see the correlation between the two events appear with the autopsy data.

"Researchers are building a large body of evidence that influenza can precipitate cardiovascular events," Nichol told CIDRAP News, adding that flu has a broad impact on many body systems.

Though researchers have long known about a relationship between cardiac complications and influenza, pneumonia gets more attention because many believe it's a key marker of flu epidemic severity, Nichol said.

However, awareness of the cardiac impact of influenza seems to be growing, she said, noting that the American Heart Association and the American College of Cardiology recently recognized the benefits of influenza vaccination for patients who have heart disease.

Influenza's role as a trigger
Madjid and some other researchers believe that influenza causes severe inflammation that, in some patients, can destabilize atherosclerotic plaques in coronary arteries, which can lead to an AMI, according to the EHJ release.

Most people in Western countries have varying degrees of atherosclerosis, though most will never show any clinical signs of it, Madjid said. "However, in some patients the quiescent, stable atherosclerotic plaques undergo sudden changes, mainly due to exaggerated inflammation, leading to rupture of these vulnerable plaques and subsequent formation of clots resulting in heart attacks," he said.

Kristine Moore, MD, MPH, medical director of the Univefsity of Minnesota Center for Infectious Disease Research and Policy, publisher of CIDRAP News, said inflammation is probably not the only flu-related risk factor for cardiac events. "People with influenza often become dehydrated and have a fever; in both cases, the heart has to work harder to compensate, similar to exercise, which could be an important factor in leading to cardiovascular events," she said.

Flu shots to protect heart health
Madjid said the findings point up the importance of flu vaccination for people with cardiac risk factors. "If people can recognize that the flu vaccine has specific cardioprotective effects, then high-risk people will be more likely to make sure that they receive the influenza vaccine every year," he said in the news release.

The flu vaccine may be especially beneficial for low-income people who have cardiac risk factors and lack access to medical care or protective cardiovascular medications. "In contrast, the flu vaccine is inexpensive, easy to administer, and could save thousands of lives every year," Madjid said.

However, Nichol said studies to date have not shown clearly that seasonal flu vaccination can lower the rate of cardiac events. Nonetheless, she said vaccination is important because it's not possible to overstate how dangerous the flu can be. "It's at our doorstep every year, and it's not the benign, trivial nuisance that many think it is," she said.

Previous research by Madjid's team has shown that a third of people who have heart disease don't consider themselves at high risk for cardiac-related flu complications, according to the EHJ release.

"Between 10% and 20% of people catch flu every year, and I have estimated that we can prevent up to 90,000 coronary deaths a year in the USA if every high-risk patient received an annual flu vaccination," Madjid asserted.

Madjid and colleagues contend that their findings have important implications for health care during a flu pandemic. Patients who have cardiovascular disease should be considered among the priority groups to receive a pandemic vaccine, they write.

Madjid M, Miller CC, Zarubaev VV, et al. Influenza epidemics and acute respiratory disease activity are associated with a surge in autopsy-confirmed coronary heart disease death: results from 8 years of autopsies in 34,892 subjects. Eur Heart J 2007; early online publication Apr17 [Abstract]

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