Flu Vaccination Association With Lower Dementia Risk, Hospitalizations

Influenza vaccination is associated with a lower risk of dementia in patients with heart failure, and a reduced risk of hospitalization, according to research presented at Heart Failure 2016 and the 3rd World Congress on Acute Heart Failure.

The dementia findings were released from a study in more than 20,000 patients presented at Heart Failure 2016 and the 3rd World Congress on Acute Heart Failure by Dr Ju-Chi Liu, director of the Division of Cardiovascular Medicine, Department of Medicine, Taipei Medical University - Shuang Ho Hospital, in New Taipei City, Taiwan.

"Previous studies have shown that there is link between impairment in cognitive function and heart failure," said Dr Liu. "Some reports have also suggested that inflammation after getting the flu might contribute to dementia. However, there are no solid data to demonstrate that influenza vaccination could decrease the relative risk of dementia in patients with heart failure."

The current study investigated whether heart failure patients who had received the flu vaccine had a lower risk of dementia. The study included all patients over 60 years of age who visited healthcare facilities in Taiwan with a diagnosis of heart failure during 2000 to 2012. Those who had dementia prior to being diagnosed with heart failure were excluded from the study. Patients were recruited from the National Health Insurance Research Dataset, which holds information on 98 percent of Taiwan residents.

The study included 20,509 patients with heart failure. Of those, 10,797 received at least once vaccination against influenza and the other 9,712 were not vaccinated during the 12 year follow-up period.

After adjusting for factors that might influence the association, the investigators found that heart failure patients who had received the flu vaccine were 35 percent less likely to develop dementia than those who had not been vaccinated. Those who had been vaccinated more than three times had a 55 percent lower dementia risk.

"We think that the flu virus can activate the immune response and cause inflammation which may injure the brain cells," said Dr Liu. "Respiratory infection during flu can induce changes in blood pressure and heart rate, referred to as an unstable haemodynamic status, which may also harm the brain tissue."

"These effects of the flu could play a role in the development of dementia, particularly in heart failure patients who already have impaired circulation in the brain," added Dr Liu. "Vaccination reduces the chance of getting the flu, which means that the associated immune activation, inflammation and unstable haemodynamic status do not occur. This could explain the reduced risk of developing dementia. The more vaccinations patients received, the less chance they had of getting the flu, which might be why they had an even lower risk of dementia."

When they examined the association by age, the researchers found that vaccinated heart failure patients had a 44 percent lower risk of dementia if they were over 70 years old and a 26 percent lower risk if they were between 60 and 69 years old. Vaccinated male heart failure patients had a 40 percent lower risk of dementia while vaccinated female heart failure patients had a 31 percent lower dementia risk.

Dr Liu said: "The risk of dementia increases with age. Therefore, the difference in risk between the vaccinated and nonvaccinated groups is more obvious in older patients. Our findings indicate that influenza vaccination plays an important role in patients with heart failure. The flu shot not only decreases the risk of respiratory infection and death from pneumonia, but may also decrease the risk of dementia in future."

He concluded: "If influenza vaccination can prevent the inflammation induced by flu, it may decrease the risk of dementia in heart failure patients. This is an important prospect for dementia prevention. More efforts are needed to ensure that patients with heart failure are vaccinated against influenza every year. Our data suggests that these patients benefit even more from vaccination than was previously thought."

And, in research presented in a late breaking trial session at Heart Failure 2016 and the 3rd World Congress on Acute Heart Failure, the flu jab was also associated with a reduced risk of hospitalization in patients with heart failure.

The study in about 60,000 patients ends the controversy over influenza vaccination in heart failure patients and provides more robust evidence for current recommendations.

Professor Kazem Rahimi, Deputy Director of The George Institute for Global Health, University of Oxford, UK, said: "Many guidelines recommend that elderly patients and those with co-morbidities including heart failure should have annual flu vaccinations to reduce the risk of adverse events."

"Uptake of the flu vaccination in heart failure patients is relatively low, ranging from less than 20 percent in low and middle income countries to 50-70 percent in high income countries like the UK," he continued. "This may partly be because there is no strong evidence to support the recommendation in these patients. In fact, there is limited evidence to suggest that vaccination may be less effective in heart failure patients than in the general population because of their blunted immune response."

More evidence has been needed on whether flu vaccinations could reduce adverse events in patients with heart failure. If a benefit was found, this would confirm current recommendations by health policy makers and provide the impetus to improve uptake. If there was no benefit, it would suggest that those guidelines that make an explicit recommendation for use in heart failure should be reconsidered.

Conduct of a randomized controlled trial would have significant practical and in some respects ethical issues. The researchers therefore used patient records for the study.

Primary care and hospital records of 4.9 million adults from the UK Department of Health's Clinical Practice Research Datalink in 1990 to 2013 were used to assess the impact of flu vaccination on the risk of cause-specific hospitalization in heart failure patients. The risk of hospitalization for cardiovascular disease, respiratory disease, and all causes was compared between a year in which a patient was vaccinated and an adjacent year when they were not, excluding the peri-vaccination period to minimize the risk of confounding.

The investigators identified 59,202 heart failure patients in the database. Flu vaccination was associated with a 30 percent lower risk of hospitalization for cardiovascular diseases, 16 percent lower risk of hospitalization due to respiratory infections, and 4 percent lower risk of all-cause hospitalization in the period 31 to 300 days after vaccination, compared with the corresponding period in an adjacent vaccination-free year.

"These findings do not suggest that influenza infection causes myocardial infarction or other cardiovascular events," said Professor Rahimi. "A more likely explanation for the reduction in risk of cardiovascular hospitalization is that vaccination reduces the likelihood of an infection which could in turn trigger cardiovascular deterioration. The relative effect seems to be smaller for respiratory infections which may be due to fact that the vast majority of these hospitalizations are not related to influenza and in our study we were not able to distinguish between the different types of respiratory infection."

The observed associations between vaccination and hospitalizations were largest 31 to 120 days after vaccination, and in younger patients (age less than 66 years). There were no differences between men and women. Professor Rahimi said: "People don't typically suffer from influenza infections in the summer so we expected the benefit to be largest in the early period after vaccination."

He added: "We also expected a stronger relationship in younger patients since we were looking at relative risks. Older patients have multiple triggers for a cardiovascular hospitalization so the relative impact of influenza infection could become smaller. The absolute benefit, however, is probably larger in older patients because they are at greater risk of an admission to hospital."

The researchers validated the findings by looking at the association between vaccination and hospitalization due to cancer, an uncorrelated outcome. As anticipated, there was no association, which supported the validity of the analysis.

Professor Rahimi said: "Despite the measures taken, we cannot entirely rule out the possibility of residual confounding explaining at least part of the observed association. But the findings do provide further evidence that there are likely worthwhile benefits and on that basis more efforts are needed to ensure that heart failure patients receive an annual flu jab."