Could Flu Vaccines Protect Against Stroke?

A new study has identified an association between receiving an influenza vaccine and a reduced risk of stroke. The research is published in the journal Neurology.

Risk factors for stroke

A stroke occurs when the blood supply to the brain is cut off, causing damage to neuronal cells that in turn affects physiological functions in the body. There are different types of strokes that can occur: ischemic – where a blockage prevents blood from reaching the brain, hemorrhagic – caused by a bleed in or around the brain and transient ischemic attacks (TIA) which are strokes that last for a short amount of time. It’s estimated that one in four people aged 25 and over will be afflicted by a stroke in their lifetime.

There are many accepted factors that account for ~80% of stroke risk, including high blood pressure, diabetes, sedentary behavior and smoking. These risks are generally long-term, and scientists are working to understand what factors might underlie short-term risk.

Infection is one stroke trigger that is considered “well known” to the research community. Studies have found that individuals with flu-like illnesses are at a higher risk of having a stroke in the days following, with one study quantifying the risk at 40% within 15 days.

“The biological mechanism is thought to be related to the systemic inflammation caused by the infection, which can promote the rupture of the atheroma plaque and precipitate the occurrence of vascular atherothrombotic events,” says Professor Francisco Jose de Abajo from the Department of Biomedical Sciences at the University of Alcalá.

If influenza-like illnesses can potentially trigger a stroke, could a vaccine to protect against influenza also have protective properties for stroke? That’s the research question addressed in a new study published in Neurology by Jose de Abajo and colleagues, focusing specifically on ischemic stroke.

Post-flu vaccine, people are 12% less likely to have a stroke

Jose de Abajo et al. utilized a primary healthcare database in Spain known as the BIFAP database. “It is a data source that collects the anonymized clinical records of primary care physicians practicing within the National Health System in Spain (which covers almost the entire population),” Jose de Abajo explains.

The version of the database used to conduct the study had data on 7.8 million patients, with an average follow-up period of more than five years. The researchers recruited a total of 3.8 million patients that had healthcare data spanning a 14-year follow-up period (2002–2015), aged between 40 and 99-years-old as ischemic stroke in younger people is uncommon. “In that group of patients, more than 14,000 stroke cases were identified during the aforementioned period and more than 70,000 age- and sex-matched control patients were randomly selected,” Jose de Abajo says. “In the cases group, it turned out that roughly 50% [of participants] were men and 50% women, with an average age of 74.7 years. Previous studies have shown that BIFAP database is highly representative of the Spanish population.”

Analyzing healthcare records, the researchers determined whether participants had received an influenza vaccine at least 14 days prior to their first stroke, or before that same time-period in those that did not have a stroke.

In total, 41.4% of individuals that received a flu shot had a stroke, compared to 40.5% that had not. When the researchers accounted for other factors in their data, the difference in stroke prevalence shifted. “We took into account factors that could be related to both influenza vaccination and risk of stroke, which in epidemiology are known as confounding factors,” says Jose de Abajo. “We adjusted for dozens of them; some examples are comorbidities such as ischemic heart disease (previous infarct or angina), diabetes, heart failure, peripheral artery disease or chronic renal failure and risk factors such as hypertension, smoking, obesity or hypercholesterolemia.”

The research team also adjusted for pharmacological treatments, such as the use of drugs for cardiovascular and metabolic diseases. After accounting for these confounding factors, they found that individuals who had received an influenza vaccine were 12% less likely to have a stroke than those who had not. The researchers did not evaluate which influenza vaccines had been administered, but Jose de Abajo says that the team do not expect much difference between them with respect to this specific outcome.

Moving towards larger studies across different countries

The research is observational in nature, and therefore cannot determine causation between flu vaccines and stroke protection, but it does provide evidence of an association.

“Ideally, a very large randomized clinical trial would be performed, but it is unrealistic to think that such a large trial be implemented in the general population,” Jose de Abajo says. The next logical steps – in the researchers’ opinions – is to confirm their data using other sources from different countries, and using a variety of study designs, such as longitudinal cohort studies.

“The importance [of this work] lies in the fact that influenza vaccination not only prevents the infection, a disease that can be severe in certain groups, but it may also provide additional cardiovascular protection,” says Jose de Abajo. “Flu vaccination coverage in most countries is below the WHO recommended target and we hope that studies such as ours will help to raise public awareness of the benefits of vaccination and increase coverage as part of preventive public health activities,” he concludes.

Professor Francisco Jose de Abajo was speaking to Molly Campbell, Senior Science Writer for Technology Networks.

Reference: Rodríguez-Martín S, Barreira-Hernández D, Gil M et al. Influenza vaccination and risk of ischemic stroke: A population-based case-control study. Neurology. 2022:10.1212/WNL.0000000000201123. doi:10.1212/WNL.0000000000201123.