Risk of Stroke and Myocardial Infarction After Herpes Zoster in Older Adults in a US Community Population

doi:10.1016/j.mayocp.2015.09.015

Mayo Clinic Proceedings

Volume 91, Issue 1, January 2016, Pages 33-44

https://doi.org/10.1016/j.mayocp.2015.09.015 Get rights and content

Abstract

Objective

To assess the risk of stroke and myocardial infarction (MI) after herpes zoster in a US community population of older adults.

Patients and Methods

We performed a community cohort study (January 1, 1986, to October 1, 2011) comparing the risk of stroke and MI in 4862 adult residents of Olmsted County, Minnesota, 50 years and older with and without herpes zoster and 19,433 sex- and age-matched individuals with no history of herpes zoster. Odds ratios are presented for MI and stroke at 3, 6, 12, and 36 months after index herpes zoster plus hazard ratios for long-term risk (up to 28.6 years).

Results

Individuals with herpes zoster had more risk or confounding factors for MI and stroke, suggesting that they had worse health status overall. When controlling for the multiple risk factors, those with herpes zoster were at increased risk for stroke at 3 months after herpes zoster compared with those without a history of herpes zoster (odds ratio, 1.53; 95% CI, 1.10-2.33; P=.04). The association between herpes zoster and MI at 3 months was not robust across analytic methods. Herpes zoster was not associated with an increased risk of stroke or MI at any point beyond 3 months.

Conclusions

Herpes zoster was associated with only a short-term increased risk of stroke, which may be preventable with the prevention of herpes zoster.

Section snippets

Study Design

This is a retrospective study of a population-based cohort of older adults with herpes zoster comparing the rates of post–herpes zoster MI and stroke with a cohort of age- and sex-matched individuals from the same community who had no medical record history of herpes zoster. Patients were followed up for a mean of 7.1 years (range, 0-28.6 years). All adults 50 years and older with a confirmed herpes zoster episode from January 1, 1986, to October 1, 2011 (n = 4862) were included in the herpes

Results

The 4862 patients with herpes zoster and the 19,433 patients without herpes zoster had substantial rates of morbidity and multimorbidity diagnosed before the index date (Table 1). The rates of chronic conditions were higher among the patients with herpes zoster than among the patients without herpes zoster when stratifying by 1 to 3 or more chronic conditions: 1 condition, 24.7% vs 23.1%; 2 conditions, 21.3% vs 17.5%; and 3 or more conditions, 27.7% vs 21.7% for cases and controls, respectively

Discussion

In our geographically defined US population of older adults, herpes zoster was associated with an increased risk of stroke for 3 months after herpes zoster even when controlling for multiple risk and confounding factors. The association was robust across multiple analytic strategies. The association between MI and herpes zoster was less strong and not robust across different analytic methods, suggesting that this association requires additional evaluation in larger data sets. No increased risk

Conclusion

In adults 50 years and older, herpes zoster is associated with an increased risk of stroke and possibly MI in the first 90 days but not thereafter. Use of herpes zoster vaccine may prevent herpes zoster and, therefore, the associated acute increased risk.

Acknowledgments

We thank Marina Hoffman for editorial assistance and Cathy Allen for word processing and formatting.

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Risk of, and risk factors for, vasculopathy associated with acute herpes zoster
2023, Journal of Stroke and Cerebrovascular Diseases
Citation Excerpt :
This study also assessed the risk of MI after HZ, but the association at 3 months was not robust across analytic methods.8 HZ was not associated with an increased risk of stroke or MI at any time after 3 months.8 A nationwide, retrospective cohort study in Taiwan used administrative data and showed a significant increase in the incidence of stroke up to 1 year after the onset of acute HZ (adjusted hazard ratio [HR] 1.31 [95% CI, 1.06–1.60]), with an even greater increase after HZ ophthalmicus (adjusted HR 4.28 [95% CI, 2.01–9.03]) [Fig. 1; Table S1].17
We aimed to summarize the known risk of vasculopathy (stroke, myocardial infarction [MI], and transient ischemic attack [TIA]) after herpes zoster (HZ) and the impact of antiviral treatment and vaccination against HZ on the risk of vasculopathy.
A narrative literature review was conducted in PubMed to identify evidence published in the past 15 years that was relevant to the scope of this article.
Ten studies reported that HZ was associated with an increased risk of stroke and one UK study reported no association. Four studies reported that HZ was associated with an increased risk of MI, and four reported that HZ was associated with an increased risk of TIA. Two studies reported that antiviral treatment was associated with a reduced risk of stroke and an additional two studies reported no association between antiviral treatment and the risk of stroke. In addition, two studies reported that vaccination against HZ using the live zoster vaccine (ZVL) was associated with a reduced risk of stroke, and an additional two studies reported that the risk of stroke or MI after HZ was similar between ZVL vaccinated and unvaccinated individuals.
HZ is associated with an increased risk of stroke, MI, or TIA (strongest association is between HZ and stroke). Further studies are needed to determine whether antiviral treatment or ZVL vaccination influence the risk of HZ-associated vasculopathy. In addition, the effect of the recombinant zoster vaccine on the risk of HZ-associated vasculopathy should be studied.
Prompt Antiviral Therapy Is Associated With Lower Risk of Cerebrovascular Accident Following Herpes Zoster Ophthalmicus
2022, American Journal of Ophthalmology
To examine risk factors associated with cerebrovascular accident (CVA) following herpes zoster ophthalmicus (HZO).
Retrospective cohort study.
Review of medical records of all patients with HZO seen at the department of Ophthalmology, Auckland District Health Board, New Zealand, between January 1, 2006, and December 31, 2016. The main outcome measure was cerebrovascular accident within 12 months of diagnosis.
A total of 869 patients diagnosed with HZO were included in the study. The median age at onset of HZO was 65.5 years (interquartile range [IQR] 52.9-75.4), and 52.5% (n=456) were male. Antiviral therapy was started in 765 participants (88.0%), not used in 95 (10.9%), and not documented in 9 participants (1.0%). Four hundred sixty-eight participants (54.9%) received prompt oral antiviral therapy (≤72 hours of rash onset). A CVA occurred in the 12 months following HZO in 14 patients (1.6%) and was most common in older patients, occurring in 2.5% aged ≥65 years, 0.7% aged 40-65 years, and 0.9% aged <40 years. Hazard of CVA was highest immediately following HZO, with median time to CVA of 2.3 months (IQR 0.8-5.9 months). Patients who received prompt acyclovir had a 76.2% lower hazard of CVA (0.9% vs 2.6%, P = .022) on multivariate analysis.
Cerebrovascular accident occurs in a low proportion of individuals within 1 year following HZO. Antiviral treatment for HZO may reduce the risk of subsequent CVA when given within 72 hours of rash onset.
Antecedent febrile illness and occurrence of stroke in West Africa: The SIREN study
2020, Journal of the Neurological Sciences
Acute infections have been posited as potential precipitants or triggers of the occurrence of stroke among adults with traditional vascular risk factors. We evaluated associations between stroke occurrence and reported febrile illness within 4 weeks (potential antecedent infections) among West Africans.
The Stroke Investigative Research and Educational Network (SIREN) is a multicenter, case-control study involving 15 sites in Ghana and Nigeria. Cases include adults aged ≥18 years with radiologically confirmed strokes. Controls were stroke-free adults matched with cased by age, gender and ethnicity. Detailed evaluations for vascular, lifestyle and psychosocial factors were performed. Participants were asked for evidence of any febrile illness within the past 4 weeks. We used conditional logistic regression to estimate adjusted odds ratios (aOR) with 95% Confidence Interval.
Among 3588 stroke cases recruited in Ghana and Nigeria between August 2014 and July 2018, 363 cases (10.1%) reported having a febrile illness within the 4 weeks prior to stroke occurrence. Having an antecedent infection was associated with stroke occurrence with an unadjusted OR of 1.19 (1.00–1.51) but aOR of 0.83 (0.59–1.17) upon adjusting for traditional vascular risk factors. Stress, aOR of 4.69 (2.59–8.50) and consumption of green vegetables 2.27 (1.35–2.85) were associated with antecedent febrile illness.
1 in 10 stroke cases reported antecedent history of febrile illness prior to occurrence of stroke but no independent association was observed in this study. Infectious exposures may be important triggers of cardiovascular events requiring further exploratory studies to better understand the role of this emerging risk factor.
Analysis of Vascular Event Risk After Herpes Zoster From 2007 to 2014 US Insurance Claims Data
2019, Mayo Clinic Proceedings
To estimate the risk of transient ischemic attack (TIA), stroke, and myocardial infarction in periods covering 4 weeks before to 52 weeks after herpes zoster (HZ) diagnosis in US adults.
This retrospective study (GSK study identifier: HO-15-15771) with matched cohorts used the Truven Health MarketScan Commercial and Medicare claims data set linked with obesity and smoking status information. Patients 18 years and older at the date of HZ diagnosis and 1-year pre- and post-HZ diagnosis continuous insurance enrollment (from January 1, 2007, through December 31, 2014) were propensity score matched to controls in terms of demographic characteristics, risk factors for vascular events, other comorbid disorders, general health, obesity, and smoking status. A post hoc sensitivity analysis was performed not matching for obesity and smoking status information. Adjusted incidence rate ratios (IRRs) were estimated using multivariate Poisson models during an aggregate period (1-month before and after the index date).
A total of 23,339 patients with HZ were matched to 46,378 controls (mean age, 56 years; 45,173 [65%] women). During the aggregate period, patients with HZ were statistically significantly more likely to suffer a TIA: IRRs for all patients and patients aged 18 to 49 years were 1.56 (95% confidence interval [CI], 1.13-2.15) and 5.12 (95% CI, 1.37-19.10), respectively (P<.05); the respective IRRs for stroke were 1.40 (95% CI, 0.93-2.11) and 8.12 (95% CI, 0.93-71.27). In the sensitivity analysis, IRRs for TIA and stroke were statistically significantly increased regardless of age.
Herpes zoster was associated with an increased risk of composite events, TIA, and stroke in adults in the period around diagnosis. More research on the HZ and vascular risk association is needed.
HO-15-15771
Interleukin-6 and type 1 interferons inhibit varicella zoster virus replication in human neurons
2018, Virology
Varicella zoster virus (VZV) is a neurotropic alphaherpesvirus that, following primary infection (varicella), establishes latency in sensory, autonomic, sympathetic and parasympathetic neurons, where it remains until reactivation (zoster). VZV-specific cell-mediated immune responses maintain VZV latency; thus, immunosuppressed and elderly persons are at risk of reactivation and associated neurological diseases. However, the cytokines produced by the immune system that control VZV in neurons are largely unknown. Therefore, to better understand how the immune system may restrict VZV in neurons, we studied interleukin-6, tumor necrosis factor-alpha and type 1 interferons for their ability to inhibit VZV replication in human neurons in vitro. Our studies revealed that VZV transcription and viral spread were significantly reduced by interleukin-6 and type 1 interferons, and to a lesser extent by tumor necrosis factor-alpha. These findings will help in understanding how the innate immune system limits virus replication in neurons in vivo.
ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [I]: anti-tumor necrosis factor-α agents)
2018, Clinical Microbiology and Infection
The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies.
To review, from an Infectious Diseases perspective, the safety profile of agents targeting tumour necrosis factor-α (TNF-α) and to suggest preventive recommendations.
Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family.
Preclinical and clinical evidence indicate that anti-TNF-α therapy (infliximab, adalimumab, golimumab, certolizumab pegol and etanercept) is associated with a two-to four-fold increase in the risk of active tuberculosis and other granulomatous conditions (mostly resulting from the reactivation of a latent infection). In addition, it may lead to the occurrence of other serious infections (bacterial, fungal, opportunistic and certain viral infections). These associated risks seem to be lower for etanercept than other agents. Screening for latent tuberculosis infection should be performed before starting anti-TNF-α therapy, followed by anti-tuberculosis therapy if appropriate. Screening for chronic hepatitis B virus (HBV) infection is also recommended, and antiviral prophylaxis may be warranted for hepatitis B surface antigen-positive individuals. No benefit is expected from the use of antibacterial, anti-Pneumocystis or antifungal prophylaxis. Pneumococcal and age-appropriate antiviral vaccinations (i.e. influenza) should be administered. Live-virus vaccines (i.e. varicella-zoster virus or measles–mumps–rubella) may be contraindicated in people receiving anti-TNF-α therapy, although additional data are needed before definitive recommendations can be made.
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View all citing articles on Scopus

: Grant Support: This study was supported by an investigator-initiated grant from Merck & Company (B.P.Y.), grant R01 AG034676 from the National Institute on Aging (B.P.Y.), and grant AG032958 from the National Institutes of Health (M.A.N., D.G.).

: Role of the Funder/Sponsor: None of the funders or sponsors had any role in the design and conduct of the study, collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

View full text

Original articleRisk of Stroke and Myocardial Infarction After Herpes Zoster in Older Adults in a US Community Population

Abstract

Objective

Patients and Methods

Results

Conclusions

Section snippets

Study Design

Results

Discussion

Conclusion

Acknowledgments

Mayo Clin Proc

Mayo Clin Proc

Mayo Clin Proc

Mayo Clin Proc

Mayo Clin Proc

Mayo Clin Proc

Mayo Clin Proc

J Clin Virol

Clinical practice: herpes zoster

N Engl J Med

Editorial commentary: varicella zoster virus infection: generally benign in kids, bad in grown-ups

Clin Infect Dis

Systematic review of incidence and complications of herpes zoster: towards a global perspective

BMJ Open

The global epidemiology of herpes zoster

Neurology

Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP)

MMWR Recomm Rep

Varicella zoster virus vasculopathy: analysis of virus-infected arteries

Neurology

Herpes zoster ophthalmicus and delayed contralateral hemiparesis: relationship of the syndrome to central nervous system granulomatous angiitis

JAMA

Association of varicella zoster virus with giant cell arteritis

Monoclon Antib Immunodiagn Immunother

Increased risk of stroke after a herpes zoster attack: a population-based follow-up study

Stroke

Herpes zoster as a risk factor for stroke and TIA: a retrospective cohort study in the UK

Neurology

Risk of stroke following herpes zoster: a self-controlled case-series study

Clin Infect Dis

The short- and long-term risk of stroke after herpes zoster: a nationwide population-based cohort study

PLoS One

Herpes zoster ophthalmicus and the risk of stroke: a population-based follow-up study

Neurology

Original article
Risk of Stroke and Myocardial Infarction After Herpes Zoster in Older Adults in a US Community Population