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Risk of Stroke after Herpes Zoster – Evidence from a German Self-Controlled Case-Series Study

View Article: PubMed Central - PubMed

ABSTRACT

Background: Herpes zoster (HZ) is caused by reactivation of the latent varicella-zoster virus (VZV). A severe complication of HZ is VZV vasculopathy which can result in ischemic or hemorrhagic stroke. The aims of our study were to assess the risk of stroke after the onset of HZ and to investigate the roles of stroke subtype, HZ location and the time interval between HZ onset and stroke.

Methods: A self-controlled case-series study was performed on a cohort of patients with incident stroke recorded in the German Pharmacoepidemiological Research Database (GePaRD), which covers about 20 million persons throughout Germany. We estimated adjusted incidence rate ratios (IRR) by comparing the rate of stroke in risk periods (i.e., periods following HZ) with the rate of stroke in control periods (i.e., periods without HZ) in the same individuals, controlling for both time-invariant and major potentially time-variant confounders.

Results: The cohort included 124,462 stroke patients, of whom 6,035 (5%) had at least one HZ diagnosis identified in GePaRD either as main hospital discharge diagnosis or as HZ treated with antivirals. The risk of stroke was about 1.3 times higher in the risk periods 3 months after HZ onset, than in the control periods (IRR: 1.29; 95% confidence interval: 1.16–1.44). An elevated risk of similar magnitude was observed for ischemic and unspecified stroke, but a 1.5-fold higher risk was observed for hemorrhagic stroke. A slightly stronger effect on the risk of stroke was also observed during the 3 months after HZ ophthalmicus (HZO) onset (1.59; 1.10–2.32). The risk was highest 3 and 4 weeks after HZ onset and decreased thereafter.

Conclusions: Our study corroborates an increased risk of stroke after HZ, which is highest 3 to 4 weeks after HZ onset. The results suggest that the risk is more pronounced after HZO and is numerically higher for hemorrhagic than for ischemic stroke.

No MeSH data available.


Related in: MedlinePlus

Definition of risk periods: (a) for primary analysis; (b) split by age group; (c) additional stratification by potential confounders (here: myocardial infarction).
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pone.0166554.g001: Definition of risk periods: (a) for primary analysis; (b) split by age group; (c) additional stratification by potential confounders (here: myocardial infarction).

Mentions: The observation time of each individual was divided into "risk periods" and "control periods". Risk periods denote the periods after a HZ onset, during which an individual was considered to have an elevated risk of stroke. For the primary analysis, the beginning of the risk period was defined as the date of HZ onset, and the end of the risk period as 91 days thereafter (Fig 1a). In a secondary analysis the end of the risk period was further divided into intervals of 1 to 14 days, 14 days to 1 month, 2 to 3 months, 4 to 6 months, and 7 to 12 months after HZ onset. Any period of follow-up that was more than 12 months, either before or after HZ onset, was considered as a control period. To account for changes in age over time, the observation period was also split into 5-year-age periods (Fig 1b). Separate analyses were performed to control for potential time-varying confounders (see below), in which the follow-up time was additionally stratified by the respective potential confounder (Fig 1c).


Risk of Stroke after Herpes Zoster – Evidence from a German Self-Controlled Case-Series Study
Definition of risk periods: (a) for primary analysis; (b) split by age group; (c) additional stratification by potential confounders (here: myocardial infarction).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120818&req=5

pone.0166554.g001: Definition of risk periods: (a) for primary analysis; (b) split by age group; (c) additional stratification by potential confounders (here: myocardial infarction).
Mentions: The observation time of each individual was divided into "risk periods" and "control periods". Risk periods denote the periods after a HZ onset, during which an individual was considered to have an elevated risk of stroke. For the primary analysis, the beginning of the risk period was defined as the date of HZ onset, and the end of the risk period as 91 days thereafter (Fig 1a). In a secondary analysis the end of the risk period was further divided into intervals of 1 to 14 days, 14 days to 1 month, 2 to 3 months, 4 to 6 months, and 7 to 12 months after HZ onset. Any period of follow-up that was more than 12 months, either before or after HZ onset, was considered as a control period. To account for changes in age over time, the observation period was also split into 5-year-age periods (Fig 1b). Separate analyses were performed to control for potential time-varying confounders (see below), in which the follow-up time was additionally stratified by the respective potential confounder (Fig 1c).

View Article: PubMed Central - PubMed

ABSTRACT

Background: Herpes zoster (HZ) is caused by reactivation of the latent varicella-zoster virus (VZV). A severe complication of HZ is VZV vasculopathy which can result in ischemic or hemorrhagic stroke. The aims of our study were to assess the risk of stroke after the onset of HZ and to investigate the roles of stroke subtype, HZ location and the time interval between HZ onset and stroke.

Methods: A self-controlled case-series study was performed on a cohort of patients with incident stroke recorded in the German Pharmacoepidemiological Research Database (GePaRD), which covers about 20 million persons throughout Germany. We estimated adjusted incidence rate ratios (IRR) by comparing the rate of stroke in risk periods (i.e., periods following HZ) with the rate of stroke in control periods (i.e., periods without HZ) in the same individuals, controlling for both time-invariant and major potentially time-variant confounders.

Results: The cohort included 124,462 stroke patients, of whom 6,035 (5%) had at least one HZ diagnosis identified in GePaRD either as main hospital discharge diagnosis or as HZ treated with antivirals. The risk of stroke was about 1.3 times higher in the risk periods 3 months after HZ onset, than in the control periods (IRR: 1.29; 95% confidence interval: 1.16–1.44). An elevated risk of similar magnitude was observed for ischemic and unspecified stroke, but a 1.5-fold higher risk was observed for hemorrhagic stroke. A slightly stronger effect on the risk of stroke was also observed during the 3 months after HZ ophthalmicus (HZO) onset (1.59; 1.10–2.32). The risk was highest 3 and 4 weeks after HZ onset and decreased thereafter.

Conclusions: Our study corroborates an increased risk of stroke after HZ, which is highest 3 to 4 weeks after HZ onset. The results suggest that the risk is more pronounced after HZO and is numerically higher for hemorrhagic than for ischemic stroke.

No MeSH data available.


Related in: MedlinePlus