Elsevier

Vaccine

Volume 32, Issue 12, 10 March 2014, Pages 1354-1361
Vaccine

Influenza and pneumococcal vaccination and risk of stroke or transient ischaemic attack—Matched case control study

https://doi.org/10.1016/j.vaccine.2014.01.029Get rights and content

Highlights

  • We investigated associations between influenza or pneumococcal vaccine and stroke or TIA.

  • We used a matched case-control design with data from United Kingdom general practice.

  • Influenza vaccination within-season was associated with 24% reduction in stroke risk.

  • Influenza vaccination was not associated with a reduced risk of TIA.

  • Pneumococcal vaccination was not associated with reduced risk of stroke or TIA.

Abstract

Background

Evidence that respiratory infections trigger stroke suggests that influenza or pneumococcal vaccination might prevent stroke. We aimed to investigate whether influenza or pneumococcal vaccination or both together were associated with reduced risk of stroke or transient ischaemic attack (TIA).

Methods

We used a matched 1:1 case-control design with data from the United Kingdom General Practice Research Database. Cases, aged 18 years or above with stroke (fatal or non-fatal) and TIA during September 2001 to August 2009, were compared with controls matched for age, sex, calendar time and practice, adjusting for cardiovascular risk factors, vaccine risk groups, comorbidity and indicators of functional ability.

Results

We included 26,784 cases of stroke and 20,227 cases of TIA with equal numbers of matched controls. Influenza vaccination within-season was associated with 24% reduction in stroke risk (adjusted OR 0.76, 95% CI 0.72 to 0.80) but no reduction in TIA (1.03, 0.98 to 1.09). Stroke risk was significantly lower with early (September to mid-November: 0.74, 0.70 to 0.78) but not later influenza vaccination (mid-November onwards: 0.92, 0.83 to 1.01). Associations persisted after multiple imputation of missing data and sensitivity analysis for unmeasured confounders. Pneumococcal vaccination was not associated with a reduction in risk of stroke (0.98, 0.94 to 1.00) or TIA (1.15, 1.08 to 1.23).

Conclusions

Influenza vaccination was associated with a 24% reduction in risk of stroke but not TIA. Pneumococcal vaccination was not associated with reduced risk of stroke or TIA. This has important implications for potential benefits of influenza vaccine.

Introduction

Stroke is an important cause of death, disability and long term illness worldwide. It affects 150,000 people in the UK annually causing substantial social and economic effects [1], [2].

Classical risk factors, such as increasing age, hypertension, smoking, diabetes and heart disease,[3] account for only 50–60% of strokes [4] raising the possibility of other important triggers [5]. Stroke is more common in winter [6]. This may be due to seasonal changes in metabolic risk factors [7] or cold-induced vascular stress [8] but both may also be linked to respiratory (e.g. influenza and pneumococcal infections) since stroke mortality mirrors peaks in winter influenza and pneumonia [9]. This poses the question of whether influenza or pneumococcal vaccine could prevent a proportion of the remaining cases.

Several case-control studies have shown increased likelihood of respiratory symptoms one to four weeks before strokes occur [5], implying that early treatment or prevention of respiratory infection might also prevent stroke. A similar link has been shown between respiratory infection and myocardial infarction [10]. Antibiotics have been found to be ineffective [11] and antivirals of doubtful effectiveness [12], but influenza or pneumococcal vaccination may be preventative for strokes.

Some observational studies have found influenza vaccination to be associated with a reduced risk of stroke [13], [14], [15], [16], [17], either alone or combined with pneumococcal vaccine [18], but other studies have not [19], [20], [21]. Because of this inconclusive evidence, we aimed to investigate the association between influenza or pneumococcal vaccination and stroke.

Section snippets

Study design and setting

We used a matched nested case-control study design. Data were extracted from the General Practice Research Database (GPRD), now called the Clinical Practice Research Datalink (CPRD), a large computerized anonymised database representative of and comprising over 5% of the population of England and Wales [22].

In England and Wales there are over 8000 general practices, each with an average of around 7000 patients cared for by 4.3 whole time equivalent general practitioners and their ancillary

Results

We included 47,011 cases comprising 26,784 cases of stroke and 20,227 cases of TIA with equal numbers of matched controls in the study (Table 1). Cases were significantly more likely to be in a vaccine risk group, have cardiovascular risk factors (except high BMI, blood pressure or total cholesterol), higher levels of comorbidity and greater numbers of GP consultations and home visits than controls (Table 1).

Influenza vaccination in adults is recommended for people aged 65 years and over and

Main findings

Influenza vaccination within-season was associated with 24% reduction in stroke risk (adjusted OR 0.76, 95% CI 0.72 to 0.80) but no reduction in TIA (1.03, 0.98 to 1.09). The risk of stroke was significantly lower with early (September to mid-November: 0.74, 0.70 to 0.78) but not later influenza vaccination (mid-November onwards: 0.92, 0.83 to 1.01). Associations persisted after multiple imputation of missing data and sensitivity analysis for unmeasured confounders. Pneumococcal vaccination was

Conflict of interest statement

All authors declare that no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Contributors

A.N.S. and C.C. had the initial idea for the study and had the main responsibility for the conception and design of the study. Z.A. undertook the data analysis supported by C.C. A.N.S. wrote the first draft of the paper. All authors interpreted the results, participated in reviewing and editing the entire report, and approved the final version to be published.

Acknowledgements

We are grateful to the Clinical Practice Research Datalink (CPRD) for providing the data for the study. This work presents independent research supported by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-0808-16254). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

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