Shingles Increases Risk for Stroke and Myocardial Infarction

Tara Haelle

December 17, 2015

An episode of shingles, caused by the herpes zoster virus, temporarily increases the risk for stroke and potentially myocardial infarction (MI) in the months after the infection, according to two recent studies.

One study, published online December 15 in PLOS Medicine, using a self-controlled case series design, identified a twofold greater risk for ischemic stroke and nearly a twofold risk for MI in the first week after shingles diagnosis. However, the risk for both incidents gradually decreased during the subsequent 6 months. Multiple previous studies have identified the link between shingles and transient risk for stroke, but fewer have linked herpes zoster to MI.

The other research, a retrospective cohort study published online December 15 in the Mayo Clinic Proceedings, similarly found an increased risk for stroke in the 3 months after shingles, but the findings of increased risk for MI disappeared after controlling for other confounders, including indicators of overall poorer health.

"[I]t is possible that an increased long-term risk of MI and stroke is due at least in part to the steeper multi-morbidity trajectory in patients with herpes zoster," write Barbara P. Yawn, MD, from Olmsted Medical Center in Rochester, Minnesota, and coauthors. The mechanism for increased risk for stroke in the 3 months after shingles diagnosis "is most likely due to productive [varicella zoster virus] infection in intracerebral arteries after transaxonal spread of virus on reactivation from cranial nerve ganglia," the authors write.

Dr Yawn and colleagues matched 4862 adults with at least one shingle episode between 1986 and 2011 by age and sex with 19,433 individuals with no history of shingles. The researchers compared the rate of incident stroke or MI during an average of 7 years in the patients, all aged 50 years and older and residents of Olmsted County, Minnesota.

Although obesity and smoking history were excluded as covariates because of poor records, the researchers adjusted their analysis for stroke risk factors identified by the US Department of Health and Human Services Taskforce in 2010, including hypertension, dyslipidemia, cardiac arrhythmias, congestive heart failure, diabetes, depression, and chronic obstructive pulmonary disease. They adjusted for vasculopathies and stroke for patients with MI and for coronary artery disease including MI in patients with stroke.

Among 4478 patients with shingles and 16,800 without (excluding those with history of stroke after confounding adjustment), those with shingles had 53% greater odds of incident stroke in the next 3 months (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.01 - 2.33) after herpes zoster diagnosis.

An analysis of 4454 individuals with shingles and 16,740 without (excluding those with MI history) initially revealed an association between MI and shingles at 3 months, 6 months, 1 year, and 3 years after herpes zoster infection, but adjustment for other risk factors only left a significant association at 3 months (P < .04). "Herpes zoster and MI are not strongly associated at any point in time using any type of analysis, and the association of MI and herpes zoster identified at 3 month by logistic regression is not robust across differing analytic approaches," the authors note.

In the PLOS Medicine study, Caroline Minassian, PhD, from the London School of Hygiene & Tropical Medicine in the United Kingdom, and colleagues examined records of 351,865 Medicare beneficiaries, aged at least 65 years, who had shingles and either a stroke or MI between 2006 and 2011. Of these, 42,954 had an ischemic stroke, and 24,237 had an MI. In a self-controlled case series method, the time between shingles and the cardiovascular event in each person is compared, with adjustments for age, to determine whether the stroke or MI occurs more frequently closer to the shingles infection.

In the first week after shingles diagnosis, risk for stroke more than doubled (incidence ratio [IR], 2.37; 95% CI, 2.17 - 2.59), and risk for MI increased 1.68 times (IR, 1.68; 95% CI, 1.47 - 1.92). Risk for stroke and MI eased off in the 6 months after shingles diagnosis. Although the researchers did not find that herpes zoster vaccination significantly mediated the risk for stroke or MI, only 2% of those with MI and 3% of those with stroke had been vaccinated, thereby limiting the power to assess vaccination influence.

"The association we observed with MI is suggestive of a systemic association rather than one localized to the brain," write Dr Minassian and coauthors. "A less marked association was observed for a secondary analysis of zoster and hemorrhagic stroke."

Among the multiple possible mechanisms for the association between shingles and stroke or MI is "that inflammation may lead to arterial thrombosis on a background of atherosclerosis," the authors suggest. "A hemodynamic mechanism is also a possible basis for the increased risk of stroke following zoster," they write, and either blood pressure elevation from shingles pain or shingles-induced "vasculopathy with arterial rupture or aneurysm formation" could increase risk for hemorrhagic stroke.

The Minassian study was supported by a Wellcome Trust Senior Fellowship in Clinical Science, the Stroke Association, and the UK National Institute for Health Research. One coauthor has consulted for GlaxoSmithKline, and another coauthor has consulted for Gilead and GSK and holds stock in GSK. The Yawn study was supported by Merck & Company and the National Institutes of Health. The authors have disclosed no relevant financial relationships.

PLoS Med. Published online December 15, 2015. Full text

Mayo Clin Proc. Published online December 15, 2015. Abstract

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