Recombinant shingles vaccine linked to lower cardiovascular disease risk

Older adults who received the newer, recombinant shingles vaccine, also known as Shingrix, had a 9% lower cardiovascular disease burden over seven years than those who received the vaccine's discontinued, live-virus predecessor, according to a study published Aug. 26, 2026, in Nature Medicine.

Heart disease remains the leading cause of death in the U.S., and payers and providers continue to look for cost-effective ways to lower that burden. Shingles, a painful condition caused by reactivation of the dormant chickenpox virus, disproportionately affects older adults and is preventable through vaccination. The U.S. transitioned from a live attenuated shingles vaccine, Zostavax, to the recombinant version, Shingrix, starting in late 2017, according to study authors. Zostavax was pulled from the market in 2020, leaving Shingrix as the only shingles vaccine available today. A growing body of research has examined whether Shingrix offers cardiovascular benefits beyond shingles prevention itself, a question relevant to how payers value vaccination programs for older adults.

Fabiana Corsi-Zuelli of the Department of Psychiatry at the University of Oxford led the study with her team.

Earlier studies suggested Shingrix might lower cardiovascular risk, but those studies only compared vaccinated people with unvaccinated people. That's a weaker comparison, because people who choose to get vaccinated tend to differ from those who don't in ways that also affect heart disease risk—a problem researchers called "healthy-vaccinee bias."

To avoid that problem, her team used a "natural experiment": the rapid U.S. switch from Zostavax to Shingrix in 2017 created two groups of vaccinated people, separated only by which vaccine happened to be available when they got their shot.

The study used deidentified electronic health record data from the TriNetX US Collaborative Network, which draws on roughly 60 health care organizations. Her team matched 36,460 adults 60 and older who got their first shingles vaccine dose between April and September 2018, when 93.5% of doses given were Shingrix, to 36,460 people vaccinated in the same window in 2017, when 98.6% of doses were Zostavax. The two groups were matched on 83 characteristics, including demographics, health conditions and medications; people with blood cancers, immune deficiencies or recent immune-suppressing treatment were excluded.

The primary analysis tracked cardiovascular diagnoses for up to seven years using the restricted mean time lost ratio, a measure of how much longer, on average, people in each group went before being diagnosed with cardiovascular disease. Her team also ran several supporting analyses, including one accounting for the competing risk of death from other causes and others testing different time windows for measuring health status before vaccination.

T was found that those who got Shingrix had a 9% lower composite cardiovascular burden over seven years, a difference that could translate into hundreds of thousands of prevented cases nationally if confirmed. The reduction was driven mainly by lower rates of ischemic heart disease (10% lower burden) and heart failure (12% lower burden), both consistent in men and women. Ischemic stroke was 12% lower among men but showed no significant difference among women or overall.

Shingrix was also linked to a 7% lower burden of atrial fibrillation, a secondary outcome, but there were no significant differences for heart attacks involving complete blockages, myocarditis, peripheral artery disease, mini-strokes or bleeding strokes. The association was strongest in the first 3.5 years and weakened over the second half of follow-up. Results held up across supporting analyses, including one accounting for competing mortality risk and one limited to before the COVID-19 pandemic.

Her team said the biological explanation isn't yet clear, but pointed to the AS01 adjuvant in Shingrix, which other research has linked to lasting changes in immune cell activity, including reduced interleukin-6 signaling tied separately to lower cardiovascular risk. They said the effect is unlikely to be fully explained by Shingrix's greater effectiveness at preventing shingles itself, since the reduction in shingles cases between the two groups was smaller than the reduction in ischemic heart disease.

"The biological mechanisms underlying these observations remain to be clarified experimentally," the team wrote. For payers and health systems, the findings add to the case for shingles vaccination in populations already prioritized under current guidelines, though the team stopped short of framing the results as reason to change vaccination policy on their own.

This study design is a strength, because it avoids the kind of bias that weakened earlier studies comparing vaccinated and unvaccinated people. The team also ran extensive checks to confirm its main finding. One check looked at an unrelated health condition that shouldn't be affected by the vaccine at all — and, as expected, it found no difference between the two groups.

However, the study relied on electronic health record data, which can miss undiagnosed cases and lacks detailed socioeconomic and lifestyle information, such as smoking, diet and alcohol use, that could differ between groups. The findings are observational, not from a randomized trial, so they show an association rather than proof the vaccine causes lower cardiovascular risk. The team also assumed, based on separate research, that Zostavax had no independent effect on cardiovascular risk, an assumption the study design could not directly test.

Corsi-Zuelli's team concluded that the results "justify clinical trials and mechanistic studies to investigate potential cardioprotective effects of shingles vaccines." Given the global burden of cardiovascular disease, they wrote, the findings, if confirmed in clinical trials, "would have important implications for public health."