Shingles vaccination reduced major adverse cardiac events and secondary cardiovascular outcomes for patients with atherosclerotic cardiovascular disease, according to new research.

The research, presented at the American College of Cardiology (ACC) Scientific Session 2026, comes on the heels of a growing body of evidence suggesting that the herpes zoster vaccine may reduce the risk for major cardiovascular events, said study co-author Robert Nguyen, MD.

“Given the ongoing burden of cardiovascular disease, particularly among high-risk populations, we wanted to better understand whether this association holds true in patients with established atherosclerotic cardiovascular disease,” Nguyen, resident at the University of California, Riverside, told Medscape Medical News. “Our goal was to contribute meaningful data that could help clinicians and patients make more informed decisions — especially in an era where misinformation and vaccine hesitancy remain significant challenges.”

The retrospective cohort study involved patients aged 50 years or older from the US TriNetX database. Patients received a diagnosis of atherosclerotic cardiovascular disease between January 1, 2018, and January 1, 2024.

Exclusion criteria were a diagnosis of autoimmune disease or previous herpes zoster complications before the index date. Researchers used propensity score matching to balance demographics and comorbidities, such as age, sex, race, cigarette smoking, and disease comorbidities.

Overall, the study included 275,304 patients vaccinated for herpes zoster and 275,304 unvaccinated patients. The total population was about 60% men, 76% White, and 11% Black.

Results showed herpes zoster vaccination lowered the risk for major adverse cardiac events (hazard ratio [HR], 0.54; 95% CI, 0.52-0.55), all-cause mortality (HR, 0.39; 95% CI, 0.38-0.41), incident myocardial infarction (HR, 0.73; 95% CI, 0.70-0.76), and stroke (HR, 0.73; 95% CI, 0.70-0.77).

The risks for incident venous thromboembolism (HR, 0.63; 95% CI, 0.60-0.67), heart failure (HR, 0.67; 95% CI, 0.62-0.73), and atrial fibrillation or flutter (HR, 0.70; 95% CI, 0.67-0.72) were also reduced in the vaccination group.

Possible Mechanisms of Action

Paul Heidenreich, MD, professor at the Stanford University School of Medicine in Stanford, California, who was not involved in the research, said it’s important to note the study was not randomized.

“However, the results are much stronger than observational studies for other vaccines, such as influenza,” Heidenreich told Medscape Medical News. “If the results were confounded by vaccinated people being healthier in ways that could not be controlled for in the analysis, then we would expect a similar effect with observational studies of flu vaccination. Given the herpes zoster effect is much larger, it is likely that herpes zoster vaccination is reducing the known herpes zoster vasculopathy and increased inflammation that occur with reactivation of herpes zoster infection.”

Nguyen noted that vaccination primes the immune system, which may help attenuate the severity of infection if it does occur, potentially blunting the downstream inflammatory cascade.

“So, the benefit may come from both preventing infection altogether and reducing the physiologic stress associated with breakthrough infections,” Nguyen said.

The Clinician’s Role

As a result of the research, Heidenreich foresees an “increased emphasis in clinical guidelines [regarding herpes vaccination] and recommendations by cardiologists to have patients vaccinated for herpes zoster to reduce vascular-related diseases,” he said.

Nguyen said clinicians will play a critical role when it comes to vaccine uptake. 

“One of the most effective strategies is simply making a strong, clear recommendation,” he said. “Many times, encouraging vaccine uptake for patients with cardiovascular disease is as important, if not more important, than encouraging patients to take their hypertension medication.”

Nguyen and Heidenreich reported having no relevant financial relationships. 

Brian Ellis is a freelance writer and editor who lives in Southwest Virginia.