Herpes zoster and major vascular events in a general population without prior cardiovascular event from Shizuoka Kokuho database

Q: What are the key findings of this study?

Incident herpes zoster was not significantly associated with major hospitalization-requiring cardiovascular events (HR 1.03, 95% CI 0.90-1.18, p=0.66) in adults without prior cardiovascular disease.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Adults without prior cardiovascular disease evaluated for herpes zoster (n=94421). Intervention: Incident herpes zoster (ICD-10 B02.2 or B02.9 with concurrent oral antiviral prescription) vs. Age-, sex-, and propensity score-matched individuals without herpes zoster. Primary outcome: Composite of unstable angina pectoris, myocardial infarction, or stroke requiring hospitalization (HR 1.03, 95% CI 0.90-1.18, p=0.66).

Q: What does this research mean for the field?

In adults without prior cardiovascular disease, incident herpes zoster is not significantly associated with an increased long-term risk of major hospitalization-requiring cardiovascular events. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Shogo Ikegami; Masato Takeuchi; Shiori Nishimura; Hiraku Kumamaru; 中丸遼; Shun Kohsaka; Masaki Ieda

doi:10.1038/s41598-026-76300-7

October 25, 2026Scientific ReportsOpen Access

Herpes zoster and major vascular events in a general population without prior cardiovascular event from Shizuoka Kokuho database

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Key result

Incident herpes zoster is not associated with major cardiovascular events in adults without prior CVD.

HR 1.03
95% CI 0.90-1.18
P=0.66
n=94,421

Why the study?

Herpes zoster is associated with cardiovascular disease risk, but findings may differ by baseline risk profile and the association among adults without prior CVD warranted evaluation.

Does incident herpes zoster increase the risk of hospitalization-requiring major cardiovascular events (unstable angina, myocardial infarction, or stroke) in adults aged 50–84 years without prior cardiovascular disease?

Key Points

To evaluate the association between herpes zoster and major cardiovascular events among adults aged 50 to 84 years without prior cardiovascular disease.
Analyzed data from a municipal-level health insurance database in Japan, identifying herpes zoster through ICD-10 diagnostic codes combined with antiviral prescriptions in adults aged 50–84 years without prior cardiovascular disease.
Performed propensity score matching to construct a cohort of 94,269 individuals (20,575 herpes zoster cases and 73,846 controls) followed for a median of 58 months, using Cox proportional hazards models to evaluate outcomes.
During the median 58-month follow-up, 1,214 individuals (1.3%) experienced the primary composite outcome of hospitalized unstable angina pectoris, myocardial infarction, or stroke.
Herpes zoster was not significantly associated with an increased risk of major cardiovascular events in the primary matched analysis (HR, 1.03; 95% CI, 0.90–1.18; p = 0.66).
A sensitivity analysis restricted to individuals with a Charlson Comorbidity Index ≥ 1 demonstrated a non-significant trend toward higher cardiovascular risk (HR, 1.33; 95% CI, 0.90–1.96).

Study Design

Type

Cohort (n=94,421)

Multicenter

Yes

Structured PICO

Does incident herpes zoster increase the risk of hospitalization-requiring major cardiovascular events (unstable angina, myocardial infarction, or stroke) in adults aged 50–84 years without prior cardiovascular disease?

P

Population

94,421 propensity-score matched Japanese adults aged 50-84 years (median age 71, 71.5% female) without prior cardiovascular disease, followed for a median of 58 months.

E

Exposure

Incident herpes zoster exposure, defined by ICD-10 diagnostic codes B02.2 (zoster with other nervous system involvement) or B02.9 (zoster without complication) accompanied by a concurrent oral antiviral prescription (acyclovir, valacyclovir, or famciclovir) within the same calendar month.

C

Comparator

Propensity-score matched (up to 1:4 ratio) and age- and sex-matched control individuals free of herpes zoster and prior cardiovascular disease at the same index month.

O

Outcome

Composite of unstable angina pectoris (ICD-10 I20), acute myocardial infarction (I21), or stroke (subarachnoid hemorrhage I60, intracerebral hemorrhage I61, or cerebral infarction I63) requiring hospitalization within the same calendar month, over a median follow-up of 58 months (IQR 41–77).composite

Main Result

Hazard Ratio: 1.03 (95% CI 0.9–1.18)

p-value: p=0.66

In a large Japanese cohort of adults aged 50–84 years free of baseline cardiovascular disease, treated herpes zoster was not associated with an increased long-term risk of severe, hospitalization-requiring cardiovascular events, although an exploratory early risk within 1–3 months (HR 2.44) was observed.

Limitations

Observational study based on administrative claims data with potential residual confounding (smoking, BMI, sBP, and HbA1c not available for full cohort; HZ vaccination status unavailable).
Exposure and outcomes were identified using administrative claims data, which may be affected by misclassification and reduced sensitivity by excluding milder outpatient events.
Assessing outcomes over the full follow-up period may have attenuated a short-lived transient increase in cardiovascular risk immediately after herpes zoster onset.
Relatively low number of events (1,214) limited statistical power to detect modest associations, particularly in subgroup analyses.
Database primarily included self-employed, unemployed, and retired individuals among those aged <75 years, limiting generalizability.
Observational study based on administrative claims data; residual confounding cannot be excluded despite propensity score matching (smoking, BMI, sBP, HbA1c, and HZ vaccination status were unavailable for the full cohort).
Exposure and outcomes were ascertained using administrative claims codes, risking misclassification and excluding milder events managed in outpatient settings.
Evaluating outcomes across the full follow-up period may have attenuated a transient early increase in cardiovascular risk immediately following herpes zoster onset.
Relatively low number of primary outcome events (1,214; 1.3%) limited statistical power to detect modest associations, especially in subgroup analyses.
Among individuals aged <75 years, the database primarily covered self-employed, unemployed, and retired persons, potentially introducing selection bias and limiting generalizability.

Implication

No long-term CV event link after herpes zoster in CVD-free adults; leaves open transient early risk for prospective study.

Abstract

Herpes zoster (HZ) is associated with a risk of cardiovascular disease (CVD), but findings may differ according to baseline risk profiles. We evaluated the association between HZ and CVD among adults without prior CVD. We used a municipal-level health insurance database in Japan. Adults aged 50–84 years without prior CVD were included. HZ was defined using ICD-10 diagnostic codes with concurrent antiviral prescription. The primary outcome was a composite of unstable angina pectoris, myocardial infarction, or stroke requiring hospitalization. Propensity score matching was performed and Cox proportional hazards models were used to estimate hazard ratios (HRs). Sensitivity analyses were conducted in individuals with Charlson Comorbidity Index ≥ 1. After propensity score matching, 94,269 individuals (20,575 HZ cases and 73,846 controls) were included. During a median follow-up of 58 months, 1,214 (1.3%) experienced the primary outcome. HZ was not significantly associated with increased risk (HR, 1.03; 95% CI, 0.90–1.18; p = 0.66). In a sensitivity analysis, HZ showed a non-significant trend toward higher risk (HR, 1.33; 95% CI, 0.90–1.96). In adults without prior CVD, HZ was not significantly associated with CVD events. However, a possible excess risk among individuals with comorbidities could not be excluded, supporting further evaluation in higher-risk populations.

Discussion

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Cite This Study

Ikegami et al. (2026) conducted a cohort in Adults without prior cardiovascular disease evaluated for herpes zoster (n=94,421). Incident herpes zoster (ICD-10 B02.2 or B02.9 with concurrent oral antiviral prescription) vs. Age-, sex-, and propensity score-matched individuals without herpes zoster was evaluated on Composite of unstable angina pectoris, myocardial infarction, or stroke requiring hospitalization (HR 1.03, 95% CI 0.90-1.18, p=0.66). Incident herpes zoster was not significantly associated with major hospitalization-requiring cardiovascular events (HR 1.03, 95% CI 0.90-1.18, p=0.66) in adults without prior cardiovascular disease.

synapsesocial.com/papers/6adfeb2da8f7ee114eb18276 https://doi.org/10.1038/s41598-026-76300-7

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Herpes zoster and major vascular events in a general population without prior cardiovascular event from Shizuoka Kokuho database

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Herpes zoster and major vascular events in a general population without prior cardiovascular event from Shizuoka Kokuho database

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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