in new findings that suggest the vaccine itself, and not just avoidance of the virus, may be beneficial.
“We postulate that influenza vaccination may have a protective effect against stroke that may be partly independent of influenza prevention,” study investigator Francisco J. de Abajo, MD, PhD, MPH, of the University of Alcalá, Madrid, said in an interview.
“Although the study is observational and this finding can also be explained by unmeasured confounding factors, we feel that a direct biological effect of vaccine cannot be ruled out and this finding opens new avenues for investigation.”
The study was published online in Neurology.
‘Not a spurious association’
While there is a well-established link between seasonal influenza and increased ischemic stroke risk, the role of flu vaccination in stroke prevention is unclear.
In the nested case-control study, researchers evaluated data from primary care practices in Spain between 2001 and 2015. They identified 14,322 patients with first-time ischemic stroke. Of these, 9,542 had noncardioembolic stroke and 4,780 had cardioembolic stroke.
Each case was matched with five controls from the population of age- and sex-matched controls without stroke (n = 71,610).
Those in the stroke group had a slightly higher rate of flu vaccination than controls, at 41.4% versus 40.5% (odds ratio, 1.05).
Adjusted analysis revealed those who received flu vaccination were less likely to experience ischemic stroke within 15-30 days of vaccination (OR, 0.79) and, to a lesser degree, over up to 150 days (OR, 0.92).
The reduced risk associated with the flu vaccine was observed with both types of ischemic stroke and appeared to offer stroke protection outside of flu season.
The reduced risk was also found in subgroup comparisons in men, women, those aged over and under 65 years, and those with intermediate and high vascular risk.
Importantly, a separate analysis of pneumococcal vaccination did not show a similar reduction in stroke risk (adjusted OR, 1.08).
“The lack of protection found with the pneumococcal vaccine actually reinforces the hypothesis that the protection of influenza vaccine is not a spurious association, as both vaccines might share the same biases and confounding factors,” Dr. de Abajo said.
Influenza infection is known to induce a systemic inflammatory response that “can precipitate atheroma plaque rupture mediated by elevated concentrations of reactive proteins and cytokines,” the investigators noted, and so, avoiding infection could prevent those effects.
The results are consistent with other studies that have shown similar findings, including recent data from the INTERSTROKE trial. However, the reduced risk observed in the current study even in years without a flu epidemic expands on previous findings.
“This finding suggests that other mechanisms different from the prevention of influenza infection – e.g., a direct biological effect – could account for the risk reduction found,” the investigators wrote.
In terms of the nature of that effect, Dr. de Abajo noted that, “at this stage, we can only speculate.
“Having said that, there are some pieces of evidence that suggest influenza vaccination may release anti-inflammatory mediators that can stabilize the atheroma plaque. This is an interesting hypothesis that should be addressed in the near future,” he added.