Flu Vaccinations Associated with Lower Hospitalization, Dementia Risk in Heart-Failure Patients

Deborah Brauser

May 31, 2016

FLORENCE, ITALY — Receiving influenza vaccinations may do more than stop a bout of seasonal flu—it can also improve outcomes in patients with heart failure (HF), according to two new studies presented here at the European Society of Cardiology (ESC) Heart Failure 2016 Congress.

The first, a registry study of more than 20,000 chronic HF patients in Taiwan, showed that, after adjustments, those who received at least one dose of the flu vaccine had a 35% lower risk of developing dementia vs those who never received the vaccine[1]. In addition, the dementia risk was 55% lower in those who had received at least three doses over the previous years.

Lead author Dr Ju-Chi Liu (Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan) told heartwire from Medscape that inflammation from a flu virus may cause injury to brain cells and play a part in dementia development, "especially in those with heart failure, who have been shown to have impaired circulatory status in the brain."

But vaccination can lower flu risk; and more vaccinations can lower the risk of flu and subsequent dementia even more, said Liu.

In the second study, which was presented at a late-breaking clinical-trial session, investigators examined records for more than 59,000 HF patients in the UK and found that those who received the flu vaccine had a 30% lower risk of CV hospitalization vs an adjacent year when they didn't receive the vaccine[2]. They also had a 16% lower risk of respiratory-infection–related hospitalization and a 4% lower risk of all-cause hospitalization.

Lead author Dr Kazem Rahimi (University of Oxford, UK) told heartwire that the results don't suggest that infection from the flu causes CV events but that the more likely explanation is that infection can act as a trigger. "And if that trigger effect is controlled by vaccination, it's likely to reduce admission to the hospital."

Past Evidence Inconsistent

Dr Kazem Rahimi

Rahimi noted that although it's been thought that vaccination "could potentially have a huge impact" on the well-being of heart-failure patients, past evidence "has been inconsistent."

His team examined electronic health records from 1990 to 2013 for 59,202 HF patients (50% men; mean age 75 years) in the UK Department of Health's Clinical Practice Research Datalink. All had at least 1 year with an influenza vaccination and 1 year without.

"We used a modified self-controlled case series design, where vaccination year was compared with adjacent vaccination-free year, irrespective of the order," explained Rahimi.

The overall effect of vaccination on hospitalizations due to CVD showed an incidence ratio of 0.70 (95% CI 0.66–0.74). The overall incidence ratio for hospitalization due to respiratory infection was 0.84 (95% CI 0.78–.90) and for hospitalization due to all-causes was 0.96 (95% CI 0.95–0.98).

Validation analyses showed no significant association between vaccination and cancer-related hospitalization.

"Most Compelling Evidence to Date"

"In the absence of randomized trials, this study provides the most compelling evidence to date for the protective effect of influenza vaccination on hospital admissions," said Rahimi.

Although the number of flu vaccinations increased significantly for HF patients after 2001, "still, only about half of the patients in our setting received annual vaccinations," he reported, adding that more needs to be done to convince these patients that getting vaccinated is beneficial to them.

After the session, official discussant Dr Arno Hoes (University Medical Center Utrecht, Netherlands) noted that although the study was not randomized, it underscores current recommendations that HF patients should be getting vaccinated.

"These observational studies are often criticized because you're not sure if you got rid of all the confounding. But this study did its very best to use methods that would limit confounding," said Hoes to heartwire . "So I think it adds to the observational evidence. Without larger trials, this is the best we have. And they did a nice job."

He added that both the old and new European heart-failure guidelines "got it right" in regard to pushing for patients to receive the vaccine. "And this study provides nice additional evidence for that."

Decreased Dementia Risk

Dr Ju-Chi Liu

In the flu and dementia study, the investigators assessed patient records from the Taiwan Longitudinal Health Insurance Database, "which includes 98% of residents of Taiwan," said Liu. All 20,509 study participants were older than 60 years of age and received a diagnosis of CHF from January 2000 through December 2012.

A total of 9712 of the participants did not receive a flu vaccination during the 12-year period examined, whereas 10,797 received at least one vaccination during that time.

The adjusted hazard ratio (HR) was 0.65 for dementia development for the participants who received an influenza vaccination vs those who did not (95% CI 0.60–0.71, P<0.001).

When the analysis was examined by age, those between the ages of 60 and 69 years who were vaccinated had an adjusted HR of 0.74 for dementia vs their unvaccinated peers. However, the risk was significantly lower for the vaccinated patients older than 70 years (HR 0.56, 95% CI 0.51–0.61; P<0.001).

And the patients in the older group who had at least three flu vaccinations had an even lower adjusted HR of 0.45 (95% CI 0.40–0.51, P<0.001).

Finally, men with HF and at least one flu vaccination had a lower dementia risk vs their female counterparts (adjusted HR 0.60 vs 0.69, respectively).

Rahimi, who was not involved with this research, urged caution when it comes to examining a short-term intervention and long-term outcomes, such as vascular dementia.

"One potential risk could be reverse causality, so that people who are healthier are more likely to receive a vaccination as opposed to vaccination reducing the risk. So causality is a bit difficult to establish." Even in his own study, "one's not 100% sure whether the effect observed is in totality attributable to vaccination."

That said, he noted that guidelines across the world should be more explicit in their recommendations about flu vaccinations in this patient population. "Certainly there's no evidence of harm and if anything, there's a substantial reduction in risks."

Rahimi added that clinicians should also provide clear information about all of this to their patients. "It should be part of a checklist so that we don't forget about any preventive measures that are likely to have an effect."

Liu and Hoes reported no relevant financial relationships. Rahimi reports receiving research grants from the National Institute for Health Research Oxford Biomedical Research Center, the Medical Research Council/Wellcome Trust, and the Oxford Martin School.

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