Researchers reveal why shingles can lead to stroke

by CU Anschutz Medical Campus

Credit: CC0 Public Domain

Scientists investigating why people who have had shingles are at a higher risk of stroke, now believe the answer lies within lipid vesicles called exosomes that shuttle proteins and genetic information between cells, according to new research from the University of Colorado Anschutz Medical Campus.

05 nov 2022--The study, published today in The Journal of Infectious Diseases, details the mechanisms behind the link between shingles and strokes.

"Most people know about the painful rash associated with shingles, but they may not know that the risk of stroke is elevated for a year after infection," said the study's lead author Andrew Bubak, Ph.D., assistant research professor in the Department of Neurology at the University of Colorado School of Medicine. "Importantly, the rash is often completely healed and individuals feel normal but nonetheless are walking around with this significant elevation in stroke risk."

Herpes zoster (HZ) or shingles is caused by the varicella zoster virus which causes chicken pox. The virus lingers in the ganglionic neurons and can reactivate causing excruciating pain. But researchers have found that shingles can also increase the risk of stroke especially for those under age 40 where the shingles vaccine is not typically recommended.

The risk is greatest in people with the rashes on their faces, perhaps due to the proximity to the brain.

To better understand how this works, Bubak and his team began looking more closely at exosomes.

"Exosomes carry pathogenic cargo that can cause thrombosis and inflammation distant from site of actual infection," Bubak said. "That could ultimately lead to a stroke in patients."

Researchers collected plasma samples from 13 patients with shingles and 10 without. The samples were taken at time of infection and at 3-month follow-ups for a subset of patients and exosomes were extracted from the plasma.

The researchers found prothrombotic exosomes which could cause blood clots in those with the infection. They also discovered proinflammatory exosomes that also pose risks for stroke at the 3-month follow-up.

Bubak said the findings suggest that in a subset of people with shingles, the virus may not return to latency or the circulating exosomes that induce a prolonged prothrombotic state may persist even after therapy is done and the rash is gone. He said using antiviral agents longer with the addition of antiplatelet and anti-inflammatory agents could help.

"As well as initiatives to increase HZ vaccine uptake to decrease stroke risk, particularly in individuals with known preexisting stroke risk factors," said Bubak. "If these findings are confirmed with a larger longitudinal study, then this could change clinical practice."

Most physicians are unaware of the connection between shingles—which has an effective vaccine—and stroke.

"But it's really important and so easily mitigated," Bubak said. "Send them home with antiplatelet agents."

More information: Zoster-associated prothrombotic plasma exosomes and increased stroke risk, The Journal of Infectious Diseases (2022). DOI: 10.1093/infdis/jiac405

Provided by CU Anschutz Medical Campus 

Shingles increases risk of heart attack, stroke

Contracting shingles, a reactivation of the chickenpox virus, increases a person's risk of stroke and heart attack, according to a research letter published today in the Journal of the American College of Cardiology.

09 july 2017--According to the Centers for Disease Control and Prevention, almost 1 out of every 3 people in the United States will develop shingles in their lifetime. Anyone who has suffered from chickenpox may develop shingles; however, the risk of shingles increases as a person gets older.
Researchers in South Korea used the National Health Insurance Service's "medical check-up" database to identify patients with newly diagnosed herpes zoster—or shingles, stroke and heart attack using the relevant International Classification of Disease-10 diagnostics codes.
A total of 519,880 patients were followed from 2003-2013, during this period there were 23,233 cases of shingles. The final cohort of 23,213 was matched with the same number of shingles-free patients to serve as control subjects.
Patients with shingles were more likely to be female and common risk factors for stroke and heart attack, such as old age, high blood pressure, diabetes and high cholesterol, were also more commonly seen in these patients. However, this group was also less likely to smoke, have a lower alcohol intake, more exercise and be part of a higher socioeconomic class.
Shingles was found to raise the risk of a composite of cardiovascular events including heart attack and stroke by 41 percent, the risk of stroke by 35 percent and the risk of heart attack by 59 percent. The risk for stroke was highest in those under 40 years old, a relatively younger population with fewer risks for atherosclerosis. The risks of both stroke and heart attack were highest the first year after the onset of shingles and decreased with time. However, these risks were evenly distributed in the shingles-free group.
"While these findings require further study into the mechanism that causes shingles patients to have an increased risk of heart attack and stroke, it is important that physicians treating these patients make them aware of their increased risk," said Sung-Han Kim, MD, PhD, a physician in the department of infectious diseases at Asan Medical Center in Seoul and one of the study authors.


Provided by American College of Cardiology

Shingles vaccine cuts chronic pain, hospitalizations

23 mar 2017--—Vaccination greatly reduces the risk of serious complications from shingles, a new study finds.
Shingles occurs when the same virus that causes chickenpox is reactivated later in life. Nearly one-third of people in the United States will develop shingles. The risk increases with age, researchers said.
The new study showed the vaccine was 74 percent effective in preventing hospitalizations for shingles during the three years after vaccination. That number dropped to 55 percent effective after four or more years.
The immunization was 57 percent effective for preventing lasting pain in the three years after vaccination. The rate dropped to 45 percent after four years, the researchers said.
The findings were published recently in the journal Clinical Infectious Diseases.
"The fact that we found relatively high effectiveness against serious outcomes, such as hospitalization and [lasting pain], and that protection from these outcomes was sustained over time, adds to the considerable evidence that the vaccine is beneficial and that seniors should be encouraged to be vaccinated in higher numbers than what is happening currently," study author Dr. Hector Izurieta said in a journal news release.
Izurieta is with the U.S. Food and Drug Administration's Center for Biologics Evaluation and Research. The FDA funded the research.
The study looked at information collected between 2007 and 2014. The data included about 2 million Medicare beneficiaries. The researchers found that the vaccine seems most effective against severe cases of shingles requiring hospitalization and against chronic pain.
There didn't seem to be much difference in how effective the vaccine was between age groups. But protection declined over time after vaccination, the researchers said.
The shingles vaccine was approved in the United States in 2006. At the time, studies showed that the vaccine reduced the risk of shingles by about half in people aged 60 and older.
In the United States, the shingles vaccine is recommended for people 60 and older. But in 2014, just 28 percent of adults in this age group said they'd received the vaccine, according to the U.S. Centers for Disease Control and Prevention.

More information: The U.S. Centers for Disease Control and Prevention has more on shingles vaccination.

Chicken pox virus may be linked to serious condition in the elderly

22 feb 2015--A new study links the virus that causes chicken pox and shingles to a condition that inflames blood vessels on the temples and scalp in the elderly, called giant cell arteritis. The study is published in the February 18, 2015, online issue of Neurology. The condition can cause sudden blindness or stroke and can be life-threatening.

The varicella zoster virus, of the herpes virus family, can cause chicken pox and may reactivate later in life in the form of shingles, a very painful rash.

"Our analysis, which is the largest to-date, provides compelling evidence that the virus also reactivates in people over 60 in another way, triggering giant cell arteritis," said study author Don Gilden, MD, Professor of Neurology at the University of Colorado School of Medicine in Denver and a Fellow of the American Academy of Neurology.

Giant cell arteritis causes swelling and tenderness of the arteries on the scalp and temples of people over the age of 50. Gilden noted that it is the most common type of inflammation of blood vessels in the elderly, affecting an estimated 29 out of 100,000 people. Symptoms include a new severe headache, scalp tenderness, jaw discomfort, blurred vision, fever, weight loss and tiredness. Importantly, the cause of this condition has been uncertain, prompting the present study.

For the study, researchers searched for evidence of the virus in 13 temporal artery biopsies of people who died and had no previous symptoms of giant cell arteritis and in 84 temporal artery biopsies of people with giant cell arteritis. All of the biopsies were from people over the age of 50.

The virus was found in 74 percent of the biopsies with giant cell arteritis and in only 8 percent of the normal skin biopsies.

"If the association can be replicated in other studies, clinical trials should focus on treating people with giant cell arteritis with a combination of the current steroid drugs used for the condition, plus anti-viral treatment for the virus," said Gilden, CBE, MD, PhD, DSc, the Burton Chair of Neurology at Glasgow University in Scotland, in a corresponding editorial.

Provided by American Academy of Neurology

Shingles May Run in the Family

By Todd Neale
HOUSTON, 20 may 2008 -- Family history appears to be a risk factor for herpes zoster, suggesting a genetic basis for susceptibility to shingles, a case-control study showed.
A significantly higher percentage of 504 patients with herpes zoster reported having a blood relative with the disease compared with 523 controls (39.3% versus 10.5%, P<0.001), Lindsey Hicks, B.S., of the University of Texas Medical School, and colleagues reported in the May issue of the Archives of Dermatology.
Those who had the disease were four-and-a-half times more likely than controls to report one affected relative (OR 4.50, 95% CI 3.15 to 6.41), with the risk increasing by almost 14 times in those with more than one relative with shingles (OR 13.77, 95% CI 5.85 to 32.39) (P<0.001 for both).
"In light of genetic advances in infectious disease susceptibility," the researchers said, "our study indicates that further studies into this area may be necessary in order to recognize and vaccinate susceptible individuals."
Known risk factors for herpes zoster include older age, illness, use of immunosuppressive therapies, and impaired immunity from diseases such as HIV or AIDS and cancer, the researchers said.
Other possible factors include sex, ethnicity, seasonality, psychological stress, physical trauma, and exposure to heavy metals.
But a possible genetic susceptibility to the disease has only recently been proposed, and family history as a risk factor has not been adequately studied, they said.
So the researchers interviewed patients who had been examined at the Center for Clinical Studies in Houston from Jan. 1, 1992 through Aug. 15, 2005 and diagnosed with herpes zoster (504) or another skin condition (523), such as psoriasis or atopic dermatitis.
Participants were not asked about use of the herpes zoster vaccine (Zostavax) because it was not approved by the FDA until 2006.
Participants with shingles were 4.35-fold more likely than controls to have a parent, sibling, or child with the disease (OR 4.35, 95% CI 3.11 to 6.09) and 4.27-fold more likely to have a non-first-degree relative with the disease (OR 4.27, 95% CI 2.44 to 7.49) (P<0.001 for both).
In a logistic regression model, sex, age, and race were not significant predictors of herpes zoster.
In regard to race, however, "our study involved predominantly white patients, and, therefore, no assumptions about racial differences in [herpes zoster] susceptibility can be made based on our data," the researchers said.
The authors said that the study may have been subjected to recall bias -- because of the self-reported family history -- and detection bias -- because controls could not adequately be evaluated for a history of herpes zoster.
However, they said, "the strength of the association found in this study between [herpes zoster] and family history suggests that bias does not completely explain our results."
In addition, they said "our study documented a dose-dependent effect between having a single blood relative and having multiple blood relatives with a history of herpes zoster."
They concluded that patients with a family history of the disease "represent a population that may be at increased risk of developing [herpes zoster] and, therefore, have a greater need for vaccination. Therefore, targeting these at-risk individuals based on their family history may decrease both their chance of future [herpes zoster] infection and healthcare expenditures toward [herpes zoster] morbidity."
Future studies, they said, are needed to confirm that this association is explained by genetic susceptibility.
The authors made no disclosures.
Primary source: Archives of DermatologySource reference:Hicks L, et al "Family history as a risk factor for herpes zoster" Arch Dermatol 2008; 144: 603-608.