Shingles Vaccine Linked to Lower Long-Term Cardiovascular Risk, Suggests Study
UK: An observational natural-experiment study found that people vaccinated against shingles during the Shingrix era had a lower risk of cardiovascular events over the following 7 years compared with those vaccinated predominantly during the Zostavax era. The findings suggest a potential cardioprotective effect of recombinant zoster vaccination, but further studies are needed to confirm causality.
The study, published in Nature Medicine, was conducted by Fabiana Corsi-Zuelli, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK, and colleagues. Researchers investigated whether the recombinant herpes zoster vaccine could be associated with a reduced cardiovascular disease burden while addressing limitations of earlier studies that compared vaccinated individuals with people who remained unvaccinated.
To reduce potential confounding, the investigators used a natural experiment created by the rapid transition in the United States from the live attenuated Zostavax vaccine to the recombinant Shingrix vaccine. They compared adults aged 60 years and older who received shingles vaccination immediately before or after this transition.
The primary analysis examined a composite cardiovascular outcome comprising ischemic heart disease, heart failure, and ischemic stroke.
Key Findings:
- Over 7 years, recombinant shingles vaccine recipients had a 9% lower cardiovascular disease burden than those vaccinated predominantly with the live attenuated vaccine (RMTL ratio, 0.91).
- The recombinant vaccine was associated with a 10% lower burden of ischemic heart disease (RMTL ratio, 0.90).
- Heart failure burden was 12% lower among recombinant vaccine recipients, with the association observed in both men and women (RMTL ratio, 0.88).
- Among men, recombinant shingles vaccination was associated with a 12% lower burden of ischemic stroke (RMTL ratio, 0.88).
- Recombinant vaccine recipients also had a 7% lower burden of atrial fibrillation (RMTL ratio, 0.93).
- No significant associations were found between recombinant shingles vaccination and other cardiac, peripheral vascular, or cerebrovascular outcomes.
The cardiovascular association became less pronounced over time, although the findings remained consistent in secondary analyses. While the natural-experiment design helped reduce some biases associated with conventional observational studies, it cannot establish that recombinant shingles vaccination directly causes cardiovascular protection.
The study had several limitations, including reliance on electronic health records and potentially unvalidated diagnostic codes, limited information on socioeconomic and lifestyle factors, and inability to assess the effects of multiple vaccine doses. The analysis also did not directly compare Shingrix with no vaccination because of the natural-experiment design.
The researchers cautioned that changes in patient characteristics and healthcare patterns following updated vaccination recommendations could have introduced unmeasured confounding. However, the absence of differences in a negative-control outcome, along with similar healthcare use, pre-vaccination clinical trajectories, and non-cardiovascular mortality, provided reassurance against major hidden biases.
The authors concluded that the association between recombinant shingles vaccination and a lower cardiovascular event burden warrants confirmation through clinical trials and mechanistic studies. If confirmed, these potential cardioprotective benefits could have important public-health implications given the substantial global burden of cardiovascular disease.
Reference:
Corsi-Zuelli, F., Li, F., Upthegrove, R. et al. Recombinant shingles vaccination and the risk of cardiovascular events. Nat Med (2026). https://doi.org/10.1038/s41591-026-04606-0
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