Shingles Vaccine Linked to Reduced Risks of Stroke, Myocardial Infarction, and Herpes Zoster Ophthalmicus

The recombinant herpes zoster vaccine (RZV, Shingrix; GSK) is well known as a highly effective preventative measure against shingles and its most common complication, postherpetic neuralgia. However, new evidence suggests its benefits may extend well beyond preventing shingles-related pain. A new study published in Clinical Infectious Diseases revealed that RZV not only lowers the incidence of herpes zoster ophthalmicus (HZO) but also lowers the risk of hospitalization for acute myocardial infarction (MI) and strokes in adults aged 50 and older.¹

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Study Findings

Researchers from Kaiser Permanente Southern California evaluated 102,766 patients who received 2 doses of the recombinant vaccine between April 2018 and December 2020, matching them with 411,064 unvaccinated controls. The median age of participants was 68 years, with 59% female and 57% white. After a median follow-up of 2.5 years, results showed significant benefits across many outcomes.¹

The incidence rate of HZO was markedly lower among vaccinated individuals compared with unvaccinated patients (0.4 vs 1.4 per 1,000 person-years). The adjusted hazard ratio (HR) was 0.271 (95% CI, 0.222-0.330), corresponding to an adjusted vaccine effectiveness of 72.9%. For cardiovascular outcomes, vaccinated patients had a lower incidence of hospitalization for acute MI (0.5 vs 0.6 per 1,000 person-years; aHR 0.720, 95% CI, 0.588-0.881) and stroke (3.3 vs 5.5 per 1,000 person-years; aHR 0.575, 95% CI, 0.533-0.619).¹

This study backs up prior evidence showing RZV effectiveness of approximately 74% against herpes zoster and 84% against postherpetic neuralgia in older adults.² Importantly, this new information shows added protection against both eye and heart issues.

Why Vaccination Impacts Cardiovascular Outcomes

The mechanisms linking shingles and cardiovascular risk have been increasingly explored. Herpes zoster has been associated with systemic inflammation, endothelial dysfunction, and transient hypercoagulability, all of which may elevate the risk of vascular events such as stroke and MI.³ By preventing shingles, RZV may indirectly lower the inflammatory burden that contributes to cardiovascular complications.

Nisha Acharya, MD, MS, of the University of California, San Francisco, noted that even patients who develop breakthrough herpes zoster following vaccination demonstrate a lower risk of cardiovascular disease compared with unvaccinated individuals.¹ This suggests that both the prevention of shingles itself and the potential immunologic effects of the vaccine may contribute to reduced vascular risks.

Implications for Ophthalmic Outcomes

Herpes zoster ophthalmicus, a reactivation of varicella zoster in the ophthalmic branch of the trigeminal nerve, affects about 10% of patients with shingles and can lead to chronic pain, vision loss, and ocular complications.⁴ The observed vaccine effectiveness of nearly 73% against HZO in this study aligns with prior reports, which estimated effectiveness between 67% and 93%.¹,⁴ This real-world evidence strengthens recommendations for vaccination in older adults, particularly given the severe morbidity associated with ophthalmic involvement.

Limitations and Considerations

Although compelling, the study had limitations. The researchers could not calculate direct vaccine effectiveness for cardiovascular outcomes, as stroke and MI were not primary endpoints. Other factors such as underlying health problems or healthcare-seeking behavior may have influenced results. Additionally, the genomic assay used in past shingle studies is not often used in clinical practice, which could impact generalizability.¹ Still, the size of the cohort and rigorous adjustments for demographic and clinical factors make the findings stronger.

REFERENCES

1. Rayens E, Sy LS, Qian L, et al. Adjuvanted recombinant zoster vaccine is effective against herpes zoster ophthalmicus, and is associated with lower risk of acute myocardial infarction and stroke in adults aged ≥50 years. Clin Infect Dis. Published online August 9, 2025. doi:10.1093/cid/ciaf440

2. Cunningham AL, Lal H, Kovac M, et al. Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older. New England Journal of Medicine. 2016;375(11):1019-1032. doi:10.1056/nejmoa1603800

3. Mbinta JF, Wang AX, Nguyen BP, et al. Herpes zoster vaccine effectiveness against herpes zoster and postherpetic neuralgia in New Zealand: a retrospective cohort study. Lancet Reg Health West Pac. 2022;31:100601. Published 2022 Sep 26. doi:10.1016/j.lanwpc.2022.100601

4. Helm MF, Khoury PA, Pakchanian H, Raiker R, Maczuga S, Foulke GT. Recombinant Zoster Vaccine Reduces 3-Year Cardiovascular Risk: Insights From a Multi-Centered Database. J Drugs Dermatol. 2023;22(12):1178-1182. doi:10.36849/JDD.7415