Time-varying association between herpes zoster infection and subsequent occurrence of stroke.

The aim of this study was to investigate the shape of the time-varying relationship between herpes zoster infection, nominally shingles, and the occurrence of stroke. Retrospective cohort study. Using the Italian Health Search Database, a cohort of patients aged ≥18 years who were registered between 2002 and 2021 was selected. In this cohort, a nested case-control analysis was used to model the time-varying distance (in months) between the dates of shingles and post-herpetic stroke, using a regression cubic spline, based on the odds of the occurrence of stroke compared with those without shingles. The dataset comprised 42,513 cases (51.1% males; mean age [stanndard deviation {SD}]: 71.0 [11.8] years) and 425,124 related controls (51.1% males; mean age [SD]: 70.9 [12] years). In the first 12 months following shingles diagnosis, a rapid increase in the risk of stroke was observed, reaching an odds ratio of 1.31 (95% confidence interval: 1.21-1.41); subsequently, there was some risk reduction and a new symmetric increase within the first 4.2 years of follow-up, thus shaping a bimodal distribution. Then, a new increase in the stroke risk was reported, although less steep, which was followed by a regular risk reduction (still 10% higher compared with those without shingles), resulting in a right-skewed relationship between the time from the shingles diagnosis and the occurrence of stroke. This association was no longer statistically significant 13.1 years after shingles diagnosis. This study demonstrated that the risk of post-herpetic stroke has a short- and long-term association according to a risk continuum relationship. These findings confirm the relevance of vaccination coverage for herpes zoster.

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