September/October 2023

Heart Health: Shingles and Heart Health
By Mark Coggins, PharmD, BCGP, FASCP
Today’s Geriatric Medicine
Vol. 16 No. 5 P. 28

What’s the Link Between the Virus and Cardiovascular Events?

Shingles is a painful, blistering rash caused by the varicella-zoster virus (VZV)—the same virus that causes chickenpox. Shingles can be debilitating and cause serious complications such as nerve damage, eye problems including blindness, and bacterial infections. Furthermore, there’s increasing evidence that shingles increases the risk of acute cardiovascular events such as heart attack and stroke.

Varicella-Zoster Virus
VZV is responsible for causing chickenpox (varicella) in childhood and shingles (herpes zoster) in adults. After the initial chickenpox infection, the virus can settle into nerve cells, including the cranial nerve ganglia, dorsal root ganglia, and autonomic ganglia, where it remains for many years in a dormant state.1 The virus can reactivate many years after a person has recovered from chickenpox, causing shingles. Factors contributing to the virus reactivating include the following:

• being older;
• having a lot of stress;
• having another illness;
• having a weakened immune system; and
• taking immunosuppressant medications.

Progression of Shingles
When VZV reactivates, it spreads down the long nerve fibers that extend from sensory cell bodies to the skin.2 Several days before the shingles rash develops, some people may experience general symptoms of a viral infection, such as fatigue, fever, chills, and headache. Burning, tingling pain, or itching in the area where the rash will develop are often the first symptoms of shingles and generally occur in a bandlike distribution on one side of the body (ie, around the waist, chest, stomach, or back). The second most common location is on one side of the face around the eye and the forehead. However, shingles can involve any body part, including internal organs. As the virus multiplies, a rash progressing to fluid-filled blisters typically occurs several days or up to two weeks after the first symptoms appear. The blisters then crust over, with the rash lasting seven to 10 days and healing completely within two to four weeks. Unbearable itching is frequently reported, and the area of the rash may be extremely sensitive. For some, even light contact can cause pain described as aching, burning, and stabbing.

Postherpetic Neuralgia
Shingles can also lead to long-term nerve pain, known as postherpetic neuralgia (PHN). PHN occurs in the areas where the shingles rash was, even after the rash clears. It can last for months or years after the rash goes away. The pain from PHN can be so severe and debilitating that it interferes with daily life. About 10% to 18% of people who get shingles will experience PHN.3 The risk of PHN increases with age, and older adults with shingles are more likely to develop PHN and experience longer-lasting and more severe pain than are younger people with shingles.

Long-Term Cardiovascular Risk Associated With Shingles
A growing number of studies have found that people who have had shingles have increased rates of acute cardiovascular events such as ischemic stroke and myocardial infarction.

A study published in 2022 in the Journal of the American Heart Association found that shingles is associated with an increased risk of experiencing a future cardiovascular event, such as heart attack or stroke.4 The prospective, longitudinal study followed three large US cohorts of more than 200,000 women and men. Participants did not have a prior history of stroke or coronary heart disease. The researchers collected information on shingles, stroke, and coronary heart disease using questionnaires collected every two years. Researchers followed participants for up to 16 years and evaluated whether those who had developed shingles were at higher risk for stroke or coronary heart disease years after the shingles episode. Data analysis found that people who had shingles at some point had a 30% higher long-term risk for a major cardiovascular event compared with those who had never had shingles. Furthermore, the elevated risk of a significant cardiovascular event may persist for ≥12 years following herpes zoster. The researchers also noted that persons with potentially immunocompromising conditions or immunosuppressive treatments are at increased risk.

In a study published in the Journal of the American College of Cardiology in 2017, researchers used a Korean health database to identify people newly diagnosed with shingles, stroke, or heart attack over 10 years.5 Among the nearly 520,000 people the researchers followed for that period, just over 23,000 were diagnosed with shingles. Researchers compared them with a similar number of people without shingles and found that shingles increased the risk of heart attack by 59% and stroke by 35%. The risk was highest during the first year after the onset of shingles and then diminished over time.

In a study published in 2015 in the journal PLOS Medicine, researchers reviewed data on more than 137,000 Medicare beneficiaries (all age 65 or older) who had been diagnosed with shingles.6 Of this group, the researchers found 42,954 cases of stroke and 24,237 cases of heart attack. People in the study who had shingles had a 2.4-fold increased risk of stroke and a 1.7-fold increased risk of heart attack during the first week following their shingles diagnoses. Although the risk gradually declined over time, it remained elevated for at least six months.

Role of Inflammation and Stress
Inflammation and stress are both thought to contribute to the risk of cardiovascular events associated with shingles.

Inflammation
When VZV reactivates, it triggers an immune response that causes widespread inflammation. This inflammation can damage the blood vessels, making them more prone to plaque buildup and clot formation. As a result, blood flow to the heart and brain can become restricted, leading to stroke and heart attacks.

Stress
Another possible contributing factor that connects shingles to heart attack and stroke is physical and emotional stress. Pain, discomfort, and concerns about the appearance of shingles rash can adversely affect a person’s quality of life, mood, and sleep. Stress can also raise blood pressure and heart rate, which can strain the heart and increase the risk of cardiovascular events.

The Shingles Vaccine
There is currently one shingles vaccine, called Shingrix (recombinant zoster vaccine), authorized for use in the United States. As of November 18, 2020, a previous shingles vaccine called Zostavax, a live vaccine containing a weakened version of VZV, is no longer available in the United States. Shingrix became preferred over Zostavax because it is more effective and longer lasting. For example, Shingrix reduces the risk of shingles by 97% and the risk of PHN by 91%.7 In comparison, Zostavax reduces the risk of shingles by 51% and the risk of PHN by 67%.8

The shingles vaccination using Shingrix consists of two doses, separated by two to six months. The CDC recommends that all healthy adults aged 50 years and older get two doses of the shingles vaccine to prevent shingles and problems after having shingles. Persons should receive the shingles vaccine even if:

• they had shingles in the past, as the vaccine will help to prevent them from getting shingles again. However, vaccination should be delayed until the shingles rash is gone;

• they are unsure if they’ve had chickenpox; or

• they received the old shingles vaccine, Zostavax.

As noted, two doses of Shingrix provide strong protection against shingles and PHN, the most common complication of shingles.7

• In adults 50 to 69 years old with healthy immune systems, Shingrix was 97% effective in preventing shingles; in adults 70 and older, Shingrix was 91% effective.

• In adults 50 years and older, Shingrix was 91% effective in preventing PHN; in adults 70 and older, Shingrix was 89% effective.

• In adults with weakened immune systems, Shingrix was between 68% and 91% effective in preventing shingles, depending on their underlying immunocompromising condition.

• In people 70 years and older who had healthy immune systems, Shingrix immunity remained high seven years following vaccination.

There’s also evidence that receiving the shingles vaccine can decrease the risk of stroke. Researchers found that the Zostavax (zoster vaccine live) vaccine lowered the risk of stroke by about 16% among older adults who received it. The effect was stronger for ischemic stroke (18%) than for hemorrhagic stroke (12%).9 In persons younger than 80 years old, the vaccine lowered stroke risk by 20%. More research is needed to determine if Shingrix offers the same benefit. However, since Shingrix is more effective in preventing infection, it is possible that it may reduce the risk of stroke more than Zostavax.

— Mark D. Coggins, PharmD, BCGP, FASCP, is vice president of pharmacy services and medication management for skilled nursing centers operated by Diversicare in nine states and is a past director on the board of the American Society of Consultant Pharmacists. He was nationally recognized by the Commission for Certification in Geriatric Pharmacy with the 2010 Excellence in Geriatric Pharmacy Practice Award.

References
1. Gilden D, Mahalingam R, Nagel MA, Pugazhenthi S, Cohrs RJ. Review: the neurobiology of varicella zoster virus infection. Neuropathol Appl Neurobiol. 2011;37(5):441-463.

2. Shingles. National Institute on Aging website. https://www.nia.nih.gov/health/shingles. Updated October 12, 2021.

3. Complications of shingles. Centers for Disease Control and Prevention website. https://www.cdc.gov/shingles/about/complications.html. Updated May 10, 2023.

4. Curhan SG, Kawai K, Yawn B, Rexrode KM, Rimm EB, Curhan GC. Herpes zoster and long-term risk of cardiovascular disease. J Am Heart Assoc. 2022;11(23):e027451.

5. Kim M, Yun S, Lee H, et al. Herpes zoster increases the risk of stroke and myocardial infarction. J Am Coll Cardiol. 2017;70(2):295-296.

6. Minassian C, Thomas SL, Smeeth L, Douglas I, Brauer R, Langan SM. Acute cardiovascular events after herpes zoster: a self-controlled case series analysis in vaccinated and unvaccinated older residents of the United States. PLoS Med. 2015;12(12):e1001919.

7. Shingles vaccination. Centers for Disease Control and Prevention website. https://www.cdc.gov/vaccines/vpd/shingles/public/shingrix/index.html. Updated May 8, 2023.

8. What everyone should know about Zostavax. Centers for Disease Control and Prevention website. https://www.cdc.gov/vaccines/vpd/shingles/public/zostavax/index.html. Updated October 5, 2020.

9. Yang Q, Chang A, Tong X, Merritt R. Herpes zoster vaccine live and risk of stroke among Medicare beneficiaries: a population-based cohort study. Stroke. 2021;52(5):1712-1721.