Abstract

The problem
Stroke is an important cause of death and long term illness worldwide. About 150 thousand people suffer a new or recurrent stroke each year in the United Kingdom and five percent of the population are affected. Many of those who have a stroke survive but suffer substantial disability and considerable social and economic distress. Strokes are more common in winter and after respiratory infections, such as influenza and pneumonia. This suggests that preventing respiratory infections might reduce the risk of stroke. There is insufficient and contradictory evidence for the effect of influenza and pneumococcal vaccination in preventing stroke/TIA. We aimed to investigate the association between influenza and pneumococcal vaccination with stroke/TIA.
The approach
We used a matched case-control design with data from the United Kingdom General Practice Research Database. Cases were aged at least 18 years at diagnosis of first stroke/TIA recorded between 01/09/2001 to 31/08/2009, with controls matched for sex, practice, age and calendar time. Data were analysed using conditional logistic regression, adjusted for vaccine risk groups, cardiovascular risk factors and drug treatments. We also adjusted further for comorbidities using the Charlson index and for functional capacity using frequency of GP consultations and home visits.
Findings
We included 94432 patients: 47216 cases and 47216 matched controls. A total of 21880 cases (46.3%) and 21383 controls (45.3%) had received influenza vaccination in the preceding season while 23306 cases (49.4%) and 21856 controls (46.3%) had received a pneumococcal vaccination at any time before the index date.
Influenza vaccination within the same season was associated with a 13% reduction in risk of stroke in older people aged 65 years and above if the vaccine was administered early in the season (OR 0.87, 95% CI 0.83 to 0.91).
Influenza vaccination in the same season as the index date was associated with a reduction in risk of stroke (adjusted odds ratio [OR] 0.90; 95% confidence interval [CI] 0.87 to 0.93); however, the reduction in risk of stroke was restricted to those aged over 65 years (adjusted OR 0.89, 95% CI 0.85 to 0.92) whereas there was no effect in those aged under 65 years (adjusted OR 0.92, 95% CI 0.83 to 1.01). Also we found that early influenza vaccination within the same season (1 September to 15 November) was associated with a significantly lower risk of stroke (adjusted OR 0.88; 95% CI 0.85 to 0.92) whereas this effect was absent with later vaccination (15 November to 31 January) (adjusted OR 1.04; 95% CI 0.97 to 1.11). The effect of influenza vaccination waned with time from vaccination with no significant effect beyond 3 months.
After sensitivity analysis for unmeasured confounding there was no reduction in risk of stroke with pneumococcal vaccination.
Consequences
Early influenza vaccination in older people may confer additional benefits through reduction in stroke risk. This has important implications for the early administration of influenza vaccines. Pneumococcal vaccination within the previous five years was not associated with reduced odds of stroke/TIA. Our findings suggest that influenza vaccination may have additional benefits, over and above prevention of respiratory complications, in preventing stroke/TIA. Further experimental studies are needed.