Herpes Zoster as a Trigger of Cardiovascular Events: A Systematic Review of Epidemiological Evidence and Pathophysiological Mechanisms

Herpes zoster (HZ) has been associated with acute cardiovascular and cerebrovascular events, particularly stroke. We systematically reviewed epidemiological evidence and biological mechanisms linking HZ to vascular outcomes. PubMed/MEDLINE, Scopus, Web of Science, and Embase were searched for observational studies evaluating cardiovascular or cerebrovascular events after HZ or herpes zoster ophthalmicus (HZO). Cohort, case-control, self-controlled case-series, and case-crossover studies were eligible. Mechanistic reports were considered separately to assess biological plausibility. Of 594 records identified, 204 were screened, 11 full-text reports were assessed, and 5 epidemiological studies were included in the primary synthesis. Stroke showed the most consistent association with HZ. Risk was greatest during the first weeks and months after infection, with self-controlled analyses indicating a peak approximately 3-4 weeks after HZ onset. HZO was associated with greater cerebrovascular risk than general HZ. Evidence for myocardial infarction and peripheral arterial disease was suggestive but less consistent. Mechanistic evidence supported roles for varicella-zoster virus-associated vasculopathy, inflammation, endothelial dysfunction, thrombosis, vascular remodeling, and plaque destabilization. Clinically manifest HZ is associated with a transient increase in vascular risk, most consistently for stroke. The temporal pattern and stronger association after HZO support HZ as a potential acute vascular trigger, while evidence for myocardial infarction and other vascular outcomes remains less robust.