Shingles is linked to an increased risk for both major cardiovascular events and dementia, but vaccination against herpes zoster is associated with a reduced risk for both of these in those who experience breakthrough infections over 5 years, according to a study presented at Infectious Disease Week (IDWeek) 2025 Annual Meeting in Atlanta.

A separate study from the same authors found that shingles in people with HIV is associated with triple the risk for major cardiovascular events, including a fivefold greater risk for heart attack and triple the risk for ischemic stroke, and with a more than doubled risk for dementia. Those with HIV vaccinated against shingles, however, saw those risk cut down by a third to a half.

“Shingles is really more than just a rash,” said Ali Dehghani, DO, an internal medicine physician at Case Western Reserve University School of Medicine in Cleveland. “It seems to perturb the body in a way that puts the heart and the brain at serious risk, and it does that probably via inflammation that has been revealed in prior studies.”

With more than a million infections a year, herpes zoster affects nearly 1 in 3 adults and is now recognized as a systemic inflammatory event that has potential vascular and neurocognitive sequelae because of the virus’s ability to invade arterial walls and trigger endothelial injury and thrombosis, Dehghani said.

“The virus can inflame blood vessels and raise the risk of [blood] clots and strokes,” he elaborated in a media briefing. “Think of it as a smoldering inflammation after an infection that can last for years to come.” However, “the vaccine seems to calm that process down significantly, and that effect of calming that inflammation down seems to persist for years on end.”

The findings were not necessarily surprising, but “the reported results are pretty impressive,” said Yohei Doi, MD, PhD, a professor of medicine at the University of Pittsburgh in Pittsburgh and at Fujita Health University in Toyoake, Japan, who was not involved in either study. “It’s very exciting because we don’t have good ways to prevent these complications often.” Doi said it will be important to see the full data in peer-reviewed publications, but the findings seem to suggest a “previously unknown, potentially positive impact of adult vaccinations.”

Though the analyses are also observational and unable to show causation, the results of the second study strongly suggest that shingles has even greater risks in the HIV population but that, again, vaccination may reduce those risks.

“Obviously, we know from large studies, such as the REPRIEVE trial, that people living with HIV are already prone to accelerated vascular and cognitive aging, so with an added insult of a zoster [infection], we would expect compounded effects,” Dehghani told attendees.

His research sought to understand how significant the vascular damage could be from shingles infections, whether and how much vaccination could attenuate this damage in vaccinated people with breakthrough infections, and what medium-term outcomes were in people with HIV who received the vaccine.

Apparent Protection With Breakthrough Infections

The researchers analyzed retrospective data of adults aged 50 years or older from the TriNetX Research Network of electronic health record data from 107 health systems. In one analysis of those with an average age of 59 years, they compared outcomes among 87,051 unvaccinated adults with uncomplicated shingles with those among 87,051 unvaccinated adults with the common cold and no history of shingles. In another analysis of adults (average age, 69 years), they compared 6593 vaccinated adults who had breakthrough shingles infections with 6593 adults who had shingles and were vaccinated against pneumococcal disease but not against shingles.

Within all cohorts, the researchers excluded people with a history of complicated shingles, HIV, hepatitis B or C, transplants, or any major cardiovascular conditions or events. The compared arms were also propensity matched for 63 variables, including demographics, cardiometabolic comorbidities, various other conditions, medication exposures, and healthcare utilization metrics.

In the first analysis, unvaccinated adults who had shingles had 1.2 times greater risk for major cardiovascular events over 5 years of follow-up than those who had the common cold (hazard ratio [HR], 1.2; P < .001). Specifically, those with shingles had 1.27 greater risk for heart attack, 1.17 greater risk for ischemic stroke, 1.14 times greater risk for venous thromboembolism (P < .001 for all), and 1.27 times greater risk for hemorrhagic stroke (P = .05). Their risk was also higher for all-cause dementia (HR, 1.12; P < .001), vascular dementia (HR, 1.29; P = .016), and all-cause mortality (HR, 1.29; P < .001).

Meanwhile, vaccinated adults who had breakthrough shingles infections had a reduced risk for major cardiovascular events over 18 months of follow-up compared to those who only received the pneumococcal vaccine but not the shingles vaccine (HR, 0.74; P = .009). Their risk was also lower for ischemic stroke (HR, 0.72; P = .045) and all-cause mortality (HR, 0.63; P = .002). Decreased risks for heart attack and dementia in those vaccinated against shingles were not significant, and a reduced risk for venous thromboembolism only trended down (HR, 0.8; P = .052).

When follow-up was extended to 3.5 years, the reduced risk for major cardiovascular events (HR, 0.78; P = .008), ischemic stroke (HR, 0.76; P = .038), and all-cause mortality (HR, 0.79; P = .037) remained significant; a decreased risk for venous thromboembolism became significant (HR, 0.73; P = .005); and the risk for vascular dementia was cut in half (HR, 0.5; P = .039).

“By preventing shingles and keeping the virus quiet, the vaccine may protect both the body and the brain and overall longevity,” Dehghani said.

Similar Benefits Apparent in People With HIV

In the study of people with HIV, Dehghani’s team used the same database to conduct a similar propensity-matched analysis in adults aged 50 years or older. Adults were matched on 85 covariates, including demographics, comorbidities, other conditions, lifestyle markers, medication history, and healthcare system utilization. They excluded participants with a history of chemotherapy, transplant, end-stage renal disease, major cardiovascular events, or hepatitis B or C.

One cohort compared 1347 adults with HIV on antiretroviral therapy (ART) without a history of shingles with 1347 adults who had an uncomplicated shingles infection. The other cohort, with an average age of 56 years, compared 2715 adults with HIV on ART who received the shingles vaccine with 2715 adults with HIV on ART who received the pneumococcal vaccine but not the shingles vaccine, with the same exclusions.

In the first cohort, the risk for major cardiovascular events was tripled over 5 years in people with HIV who had shingles compared to those with no previous shingles (HR, 3.2; P < .001). Risk for heart attack was more than five times greater (HR, 5.5; P < .001), and risks were also higher for ischemic stroke (HR, 3.2; P < .001) and venous thromboembolism (HR, 1.6; P = .045). Risk for dementia was nearly three times higher in those with HIV who had a shingles infection (HR, 2.8; P = .001), but there was no significant difference in all-cause mortality between the groups.

Meanwhile, people with HIV vaccinated against shingles had a 45% reduced risk for major cardiovascular events (HR, 0.55; P = .02), a 60% reduced risk for ischemic stroke (HR, 0.43; P = .017), and a 53% reduced risk for all-cause mortality (HR, 0.47; P = .019) over 18 months of follow-up compared to those with HIV only vaccinated against pneumococcal disease. Risk for shingles was 57% lower (HR, 0.43; P = .008) in those vaccinated against shingles, and risk for severe, disseminated shingles was 65% lower (HR, 0.35; P = .019). There was no significant difference in venous thromboembolism or all-cause dementia between the groups.

When follow-up was extended out to 4 years, those with HIV vaccinated against shingles had a 30% lower risk for major cardiovascular events (HR, 0.70; P = .019) and a 38% lower risk for ischemic stroke (HR, 0.62; P = .025) than those with HIV who only received the pneumococcal vaccine. Risk was nearly cut in half in those vaccinated against shingles for all-cause dementia (HR, 0.52; P = .002) and all-cause mortality (HR, 0.54; P < .001). Risk for shingles (HR, 0.51; P = .005) was also lower, though reduced risk for severe/disseminated shingles was not significant (HR, 0.48; P = .061).

“It seems, by all accounts, the vaccine is doing what it’s supposed to do and stopping the rash and also having these cardio-cognitive benefits as well,” Dehghani said.

The takeaway messages from these studies on shingles vaccination come at a particularly important time when skepticism of vaccination’s benefits have been on the rise, Doi suggested.

“Everyone knows someone who’s suffered from shingles, and it’s impacted their quality of life,” Doi told Medscape Medical News. “It seems to go away after a while, more or less, for most people, but down the line, there might be more serious consequences, and we’re maybe seeing a glimpse of that, which vaccination may address to some extent. I’m hoping these findings and, more broadly, the off-target long-term benefits of vaccination,” beyond simply preventing infectious disease, become something people see as contributing to overall better health, Doi said.

Neither study used external funding, and the authors reported having no disclosures. Doi reported advising/consulting with GSK, Meiji Seika Pharma, and Shionogi, all unrelated to this topic. 

Tara Haelle is a science/health journalist based in Dallas.