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People over 35 who have a confirmed case of influenza are at increased risk of having a heart attack in the week after their flu diagnosis, according to a new study, published in the midst of a particularly nasty flu season.

The notion that a bout of flu increases the risk of other illnesses, including heart attack, is not new. But lead author Dr. Jeffrey Kwong said this study, published Wednesday in the New England Journal of Medicine, is the first to positively link heart attacks to laboratory-confirmed cases of flu.

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Most influenza cases are never diagnosed by a medical professional; people with a mild infection often just tough it out at home. And even those sick enough to drag themselves to a doctor may be diagnosed based on their symptoms alone.

Previous studies have looked for — and found — increased rates of heart attacks during influenza season. But multiple viruses that cause flu-like symptoms also make the rounds in winter, so without a positive lab test, you can’t rule out the possibility that other viruses might have contributed to the increase in heart attacks in those studies.

“Now we can say that this is influenza, without a question, that is associated with MI,” said Kwong, using shorthand for myocardial infarction, the medical term for a heart attack.

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Kwong is a scientist at Public Health Ontario and the Institute for Clinical Evaluative Sciences in Toronto.

He and his co-authors used health records from Ontario — Canada’s most populous province — to look for people who had both a laboratory-confirmed diagnosis of influenza and a heart attack in the year preceding and the year following the flu diagnosis. They drew data from records of all Ontario residents aged 35 and older who were tested for a respiratory viral infection from May 1, 2009 to May 31, 2014, finding just over 19,000 people had positive flu tests during the period.

If flu infection increases the risk of heart attack, heart attacks should occur shortly after the flu diagnosis, the authors reasoned. So they focused in particular on the seven days following the flu diagnosis, comparing the number of heart attacks that occurred within that window to those that happened over the rest of the two-year period.

They found 332 people who had been hospitalized with one or more heart attacks within the two-year time frame. Of the 364 total hospitalizations, most — 344 — were spread out over the 52 weeks before the diagnosis or the 51 weeks after it.

But 20 were clustered in the seven days after a flu diagnosis, suggesting that there is a link between having the flu and having a heart attack — at least among people aged 35 and older. That cutoff was used, Kwong said, because heart attacks are “exceedingly rare” among people younger than 35.

The paper suggested this represents a sixfold increase in risk, meaning that people in the group studied were six times more likely to have a heart attack in the week after their flu diagnosis than in any other week in the year before and the year after.

Marc Lipsitch, an infectious diseases epidemiologist at Harvard T. H. Chan School of Public Health, said the paper was a sound addition to what’s known about influenza’s potential to trigger heart attacks.

But Lipsitch — who was not involved in the study — cautioned against drawing the conclusion that the increased risk it quantified applies to the population as a whole.

The sixfold increased risk figure tells you something about people who had both a heart attack and a lab-confirmed case of flu within a two-year window — but that group is not reflective of the general population, he said.

Kwong and his co-authors acknowledge in the article that there are several limitations to the work, one of which is that the results may only apply to people whose flu infection was serious enough that they sought medical care.

“I think that there’s a lot of mild influenza infection out there that we never see,” Kwong told STAT.

So how big is the effect of flu infection on heart attack risk in the population as a whole? “Our data can’t answer that question,” Kwong said. “Probably lower than [sixfold]. But how much lower? That’s hard to say.”

Correction: An earlier version of this story incorrectly stated the number of people found to have been hospitalized for a heart attack in the study period.  

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