Herpes Zoster Associated With Elevated Risk of Stroke, Cerebrovascular Events

Patients exposed to herpes zoster (HZ) or HZ ophthalmicus (HZO) face an increased risk of cerebrovascular events, according to a study published in the Journal of Clinical Medicine. This risk decreased gradually according to age and length of time after an HZ episode, but epidemiological studies and the pathology of VZV vasculopathy both indicate that HZ is a key risk factor for stroke up to 1 year following an HZ episode.

The investigators used 15 epidemiological studies from Asia, Europe, and the United States, each demonstrating an increased incidence of stroke or myocardial infarction in patients with a recent history of zoster. They found that these individuals had between a 1.3- and 4-fold increased risk of cerebrovascular events. Higher risks were found for patients under 40 years of age within 1 year of an HZ episode. Three of the reviewed studies found that the risk of stroke increased within the first week following an HZ episode, then decreased after 6 to 12 months.

Multiple studies concluded that the inflammatory vasculopathy caused by the varicella zoster virus (VZV) was associated with an increased risk of future cardiovascular outcomes. The virus induces vasculopathy by inducing the production of prothrombotic autoimmune antibodies—circulating immune complexes that result in autoimmune phenomenon—and disrupting the internal elastic lamina, intimal hyperplasia, and decreased smooth muscle cells in the tunica medial layer. VZV vasculopathy can cause pathological vascular remodeling, resulting in clinical ischemic or hemorrhagic stroke.

HZO, the reactivation of HZ in the ophthalmic branch of the trigeminal nerve—which provides sensation to the eyes and forehead—has been associated with a 3-fold increase in risk of stroke between 5 and 12 weeks following presentation. Further, according to the investigators, studies have demonstrated that stroke risk increases by 1.5 times up to 3 months following an HZO episode. A meta-analysis of 3 studies, intended to demonstrate increased stroke risk relating to HZ, found a pooled relative risk of 2.62, but with high heterogeneity.

The study found that vascular events occurring within days of an HZ episode may be attributable to the inflammatory response associated with HZ. The researchers provided the example that inflammatory cytokines are significantly increased in VZV infections that are related to arterial thrombosis, and that inflammation is a key component of the etiology of ischemic stroke. They hypothesize that inflammatory cells may contribute to vascular remodeling through the secretion of soluble factors and the potential disruption of pre-existing atherosclerotic plaques.

According to the study authors, there are currently limited reports indicating a reduce in stroke risk from antiviral treatment for HZ. They said that further studies are necessary to determine whether or not there is an impact on the burden of cerebrovascular and cardiovascular disease from optimal antiviral treatment.

REFERENCE

Wu, PH; Chuang, YS; Lin, YT. Does Herpes Zoster Increase the Risk of Stroke and Myocardial Infarction? A Comprehensive Review. J. Clin. Med. 2019, 8(4), 547; doi:10.3390/jcm8040547