218. Impact of Prior Zoster Vaccination on Cardiovascular, Dementia, and Mortality Outcomes Following Herpes Zoster Infection: A Matched Cohort Study

TL;DR

This study shows that prior zoster vaccination reduces long-term risks of heart issues, dementia, and death in older adults who develop shingles.

Contribution

The study demonstrates that zoster vaccination lowers risks of major adverse cardiovascular events, dementia, and mortality after shingles infection.

Findings

Zoster vaccination was associated with a 41% lower risk of all-cause mortality after HZ.

Vaccinated individuals had a 21% lower risk of major adverse cardiovascular events.

Vaccination reduced the risk of dementia by 16% following HZ infection.

Abstract

Herpes zoster (HZ) reactivation triggers systemic inflammation, increasing risks of vascular and neurologic complications. While vaccination reduces shingles incidence, its effect on long-term outcomes after breakthrough infections is unclear. We assessed whether prior zoster vaccination reduces major adverse cardiovascular events (MACE—myocardial infarction, stroke, pulmonary embolism, sudden cardiac death), dementia, and all-cause mortality in older adults with HZ. Secondary outcomes included psychiatric morbidity (anxiety, depression, bipolar disorder, schizophrenia) and Parkinsonism.Propensity Score Density Before and After Matching: Zoster Vaccinated vs. Unvaccinated PLWH

Propensity Score Density Before and After Matching: Zoster Vaccinated vs. Unvaccinated PLWH

Distribution of propensity scores in people living with HIV (PLWH) aged ≥50 years without prior HZ, comparing vaccinated (purple) and unvaccinated (teal) cohorts before (left) and after (right) 1:1 propensity score matching. Matching was based on demographics, ART regimen, cardiometabolic and psychiatric history, statin/antihypertensive use, and prior vaccine exposures. The post-matching plot demonstrates excellent overlap, confirming balanced covariate distribution between groups.Kaplan-Meier Survival Curve for MACE in Vaccinated vs. Unvaccinated PLWH

Kaplan-Meier Survival Curve for MACE in Vaccinated vs. Unvaccinated PLWH

Kaplan-Meier curve depicting time to first major adverse cardiovascular event (MACE) in people living with HIV (PLWH) aged ≥50 years without prior HZ, stratified by zoster vaccination status. The vaccinated cohort (purple) had significantly higher MACE-free survival compared to unvaccinated controls (teal) over a follow-up period of up to 7 years. Prior zoster vaccination was associated with a hazard ratio (HR) 0.787; 95% CI: 0.750–0.827; p=0.0001.

We conducted a retrospective matched cohort study using the TriNetX Analytics Network. Adults aged ≥50 years with a first-time HZ diagnosis were stratified by prior zoster vaccination status: vaccinated (RZV or ZVL) versus unvaccinated (no record of zoster/varicella vaccination). Individuals with prior HZ, HIV, hepatitis B or C, ESRD, CNS infections, MACE, or dementia were excluded. Propensity score matching (1:1) was performed on demographics, comorbidities, psychiatric diagnoses, prior vaccine exposures, and chronic medications. Outcomes included MACE, dementia, and all-cause mortality, psychiatric morbidity and Parkinsonism. Hazard ratios (HRs) and Kaplan-Meier analyses were used to assess outcome differences, with p < 0.05 considered statistically significant.Kaplan-Meier Survival Curve for Dementia in Vaccinated vs. Unvaccinated Adults with Herpes Zoster

Kaplan-Meier Survival Curve for Dementia in Vaccinated vs. Unvaccinated Adults with Herpes Zoster

Kaplan-Meier curve comparing dementia-free survival between vaccinated (purple) and unvaccinated (teal) adults ≥50 years who developed a first-time herpes zoster (HZ) infection. Over a follow-up of up to 7 years, prior zoster vaccination was associated with a significantly lower hazard of dementia (HR 0.839, 95% CI: 0.772–0.913; p < 0.0001).Forest Plot of Hazard Ratios for Clinical Outcomes: Zoster Vaccine vs. No Vaccine

Forest Plot of Hazard Ratios for Clinical Outcomes: Zoster Vaccine vs. No Vaccine

Forest plot illustrating hazard ratios (HRs) with 95% confidence intervals for major outcomes in adults ≥50 years following herpes zoster (HZ) infection, comparing individuals with prior zoster vaccination to unvaccinated controls. Zoster vaccination was associated with significantly reduced risk of all-cause mortality (HR 0.586), major adverse cardiovascular events (MACE: HR 0.787), and dementia (HR 0.839), all with p < 0.0001. No significant differences were observed for psychiatric morbidity (HR 0.994, p = 0.7448) or Parkinsonism (HR 1.00, p = 0.9936).

Following 1:1 matching, A total of 38,092 patients (n=19,046 per group) were followed from 90 days to 7 years post-HZ (median follow-up was 3.6 years in the vaccinated group and 3.9 years in the unvaccinated group). The mean age was 69.1 years, 65% were female, and 69% were White. Prior zoster vaccination was associated with significantly lower hazards of all-cause mortality (HR 0.586, 95% CI: 0.530–0.647; p < 0.0001), MACE (HR 0.787, 95% CI: 0.750–0.827; p < 0.0001), and dementia (HR 0.839, 95% CI: 0.772–0.913; p < 0.0001). No statistically significant differences were observed in psychiatric morbidity (HR 0.994, 95% CI: 0.959–1.030; p = 0.7448) or Parkinsonism (HR 1.00, 95% CI: 0.892–1.122; p = 0.9936).

Prior zoster vaccination reduced long-term risks of MACE, dementia, and mortality following HZ infection, supporting its role in mitigating post-viral complications.

All Authors: No reported disclosures

Figures