Association between herpes zoster infection and the risk of stroke: A population-based nested case-control study

Previous studies have shown inconsistent results regarding the association between herpes zoster (HZ) infection and stroke risk, particularly intracerebral hemorrhage (ICH). We aimed to evaluate the association between HZ infection and overall stroke, as well as ischemic stroke and ICH.

We conducted a population-based nested case-control study utilizing the Clalit Health Services database, the largest health care provider in Israel. The cohort included individuals aged ⩾25 years from 2005 to 2022, with follow-up through 2023. New stroke cases were matched with controls based on age, sex, population sector, and index date. HZ exposure was defined by International Classification of Diseases, Ninth Revision (ICD)-9 codes within 90 days prior to the index date, with concomitant acyclovir or valacyclovir treatment. Additional analyses explored longer time windows for HZ infection exposure, specifically within 1 and 5 years prior to the index date.

A total of 66,818 stroke cases were matched with 66,818 controls. HZ infection within the prior 90 days was associated with a significantly increased overall stroke odds, with adjusted odds ratio (OR) = 1.63 (95% confidence interval (CI) = 1.26-2.10). The strength of the association weakened and did not reach statistical significance with longer prior HZ exposure windows; adjusted OR = 1.12 (0.99-1.27) within 1 year and 1.07 (1.00-1.14) within 5 years. The pattern was similar for ischemic stroke and ICH, with a significant association observed only for HZ infection within the prior 90 days with adjusted ORs 1.54 (1.18-2.02) and 2.73 (1.16-6.42), respectively.

HZ infection is associated with increased stroke risk within 90 days post-infection and appears to be a stronger risk factor for ICH.