Herpes zoster as a risk factor for stroke and TIA: a retrospective cohort study in the UK

Abstract

Objectives: Stroke and TIA are recognized complications of acute herpes zoster (HZ). In this study, we evaluated HZ as a risk factor for cerebrovascular disease (stroke and TIA) and myocardial infarction (MI) in a UK population cohort.

Methods: A retrospective cohort of 106,601 HZ cases and 213,202 controls matched for age, sex, and general practice was identified from the THIN (The Health Improvement Network) general practice database. Cox proportional hazard models were used to examine the risks of stroke, TIA, and MI in cases and controls, adjusted for vascular risk factors, including body mass index >30 kg/m(2), smoking, cholesterol >6.2 mmol/L, hypertension, diabetes, ischemic heart disease, atrial fibrillation, intermittent arterial claudication, carotid stenosis, and valvular heart disease, up to 24 years (median 6.3 years) after HZ occurrence.

Results: Risk factors for vascular disease were significantly increased in cases of HZ compared with controls. Adjusted hazard ratios (AHRs) for TIA and MI but not stroke were increased in all patients with HZ (AHR [95% confidence interval]: 1.15 [1.09-1.21] and 1.10 [1.05-1.16], respectively). However, stroke, TIA, and MI were increased in cases whose HZ occurred when they were younger than 40 years (AHR [95% confidence interval]: 1.74 [1.13-2.66], 2.42 [1.34-4.36], 1.49 [1.04-2.15], respectively). Subjects younger than 40 years were significantly less likely to be asked about vascular risk factors than were older patients (p < 0.001).

Conclusion: HZ is an independent risk factor for vascular disease in the UK population, particularly for stroke, TIA, and MI in subjects affected before the age of 40 years. In older subjects, better ascertainment of vascular risk factors and earlier intervention may explain the reduction in risk of stroke after the occurrence of HZ.

Figure 1. Kaplan-Meier curves for the risk of stroke, TIA, and MI over the study follow-up period

The time to stroke (A) after the index date does not differ significantly for cases of herpes zoster and matched controls, but is significantly shorter for TIA (B) and myocardial infarction (MI) (C) in cases compared with controls.

Figure 2. Adjusted risk (hazard ratio and 95% confidence interval) of stroke, TIA, and MI by age group at index date

Risk of (A) stroke, (B) TIA, and (C) myocardial infarction (MI) by decade. (D) Time to stroke in cases and controls younger than 40 years. Hazard ratios adjusted for vascular risk factors for stroke, TIA, and MI are significantly higher for cases of herpes zoster occurring before 40 years of age compared with matched controls.