Covid Vaccination Linked to 24% Reduction in All-Cause Cardiac Events in Million-Veteran Study
Key Insights
A JAMA Internal Medicine study of over one million U.S. veterans found Covid vaccination was associated with a nearly 24% reduction in all-cause cardiac events, including heart attacks and strokes.
The protective effect was greatest among adults aged 75 and older and those with chronic kidney or lung disease, potentially preventing 3,500 major cardiac events and 2,400 deaths per million people annually.
Researchers propose that vaccines prevent silent or undiagnosed SARS-CoV-2 (search) infections from triggering endothelial inflammation and clotting cascades that lead to cardiac events.
A landmark study published Monday in JAMA Internal Medicine has found that Covid-19 (search) vaccination is associated with a nearly 24% reduction in all-cause cardiac events — including heart attacks, strokes, cardiac hospitalizations, and cardiac deaths — among a cohort of more than one million U.S. veterans. The findings suggest that the cardiovascular burden of SARS-CoV-2 (search) in the United States may be substantially larger than official statistics reflect, and that vaccination delivers meaningful heart protection extending well beyond prevention of acute respiratory illness.
The study, led by Ziyad Al-Aly, a clinician-researcher at Washington University in St. Louis and chief of research and education at the VA St. Louis Health Care System, followed veterans who received flu vaccinations at Veterans Affairs (search) health care facilities in 2024. Roughly one-third of the cohort also received a Covid-19 (search) vaccine during the same period.
A Benefit That Surprised Researchers
Over the eight months following vaccination, veterans who received a Covid shot — whether an mRNA formulation or another type — showed approximately a 38% lower risk of Covid-associated major cardiovascular events, defined as cardiac events tied to a documented Covid diagnosis. The broader and more striking finding: even when researchers examined all cardiac events regardless of whether a Covid diagnosis appeared in the record, vaccinated veterans still showed a nearly 24% lower risk.
Al-Aly's team estimated that this protective effect, if generalized, could translate to the prevention of roughly 3,500 major cardiac events and approximately 2,400 deaths per year for every one million people vaccinated. The benefit was greatest for those aged 75 and older and those with chronic conditions such as kidney and lung disease.
How SARS-CoV-2 (search) Damages the Heart — and How Vaccines Interrupt That Process
SARS-CoV-2 (search) enters cells by binding to the angiotensin-converting enzyme 2 (ACE2 (search)) receptor, which is expressed not only in lung tissue but also in cardiac muscle cells, vascular endothelial cells, and platelets. When the virus's spike protein binds to and depletes ACE2 on those cells, two damaging cascades can follow.
The first is direct: spike protein downregulates ACE2 (search) on the cell surface, disrupting the renin-angiotensin system. With ACE2 activity suppressed, angiotensin II — a potent vasoconstrictor that drives inflammation and promotes blood clot formation — accumulates without its normal counterbalance. The endothelium becomes inflamed, platelets become stickier, and small blood clots can form in coronary arteries.
The second cascade is indirect: the immune system's response to the virus can escalate into a cytokine storm, in which inflammatory signaling molecules flood the bloodstream and cause collateral damage to cardiac tissue.
Vaccines interrupt both pathways. mRNA vaccines train the immune system to recognize the spike protein before infection occurs, generating neutralizing antibodies that block the spike's ability to bind ACE2 (search). When a vaccinated person encounters SARS-CoV-2 (search) — including in a mild or asymptomatic infection that goes undetected — those antibodies prevent the spike from downregulating ACE2 on endothelial cells and triggering the inflammatory cascade.
Unrecognized Infections, Unattributed Cardiac Events
Al-Aly believes a significant fraction of cardiac events now counted in hospitals as idiopathic are in fact downstream consequences of Covid infections that patients and clinicians never identified. He described cases where individuals who felt "under the weather" did not test for Covid at the time, but then weeks later ended up in the emergency room with a cardiovascular event.
"What that really means is that those [events] are actually likely related to SARS-CoV-2 (search), that were never recognized to be so in the first place," Al-Aly told STAT.
"Despite the fact that the virus has evolved and things have mellowed down, and we no longer think of Covid infection as consequential, there is still actually a tidal wave of SARS-CoV-2 (search) that continues to circulate in the population," he added. "Much of it is only unrecognized, leading to heart problems. Much of it is unlinked or unattributed to SARS-CoV-2, because people are not testing."
Vaccine Safety and Myocarditis in Context
Early concerns about mRNA vaccines and heart health centered on myocarditis, observed primarily in young males after the second dose of original vaccine formulations in 2021 and 2022. At its peak, the myocarditis signal reached approximately 38 cases per million doses. That signal has since resolved: updated 2024-2025 and 2025-2026 vaccine formulations show myocarditis rates at or below two cases per million doses, indistinguishable from the background rate in the general population. Covid-19 (search) infection itself causes myocarditis at a rate roughly 20 times higher than current updated vaccines.
Robert Califf, a cardiologist and former FDA Commissioner who is now at Duke University, wrote an accompanying commentary on Al-Aly's findings. "There are many, many studies now that show that vaccinations of various types seem to reduce the risk of chronic diseases, including cardiovascular disease… this is not inconsistent with what the other studies have shown," Califf told STAT.
Califf also acknowledged a methodological challenge: "It's also worth keeping in mind that the testing environment has changed a lot, so knowing for sure who had a subsequent infection, that's probably the shakiest of the whole thing."
Companion Studies Reinforce Vaccine Effectiveness
The cardiovascular study appeared as part of a larger package of Covid-related research published Monday. A separate study led by Ryan Wiegand and researchers at the CDC evaluated real-world effectiveness of the 2024-2025 Covid vaccines in the United States, finding that vaccinated adults were less likely to need emergency or urgent care for Covid, with vaccine effectiveness of 41% against critical illness for adults 18 and older.
A third study, funded by the European Centre for Disease Prevention and Control and published in JAMA Network Open, found approximately 55% effectiveness in protecting adults 60 and older from symptomatic disease in the two months following vaccination across multiple European countries. The authors flagged low uptake rates as "missed opportunities for preventing symptomatic COVID-19 (search) among unvaccinated vulnerable groups."
Bill Hanage, a professor of epidemiology at Harvard T.H. Chan School of Public Health who was not involved in the studies, told STAT he found it striking that "over the short term, the Covid vaccines in the Wiegand study are roughly as effective as flu vaccines." He added, "Covid vaccines are still protective and still keep people out of hospital."
Clinical Implications and Uptake Challenges
Despite the accumulating evidence, Covid shot uptake in seniors remains less than half that of flu vaccines. The FDA in August 2025 restricted the 2025-2026 Covid vaccine's approved use to adults 65 and older and individuals ages 5 to 64 with at least one documented high-risk health condition.
"I think when you have more than half of the population, even high risk, who are not electing to get updated, people are not viewing it as a medical necessity," Califf said. "The evidence says that the benefits outweigh the risks… My general view for me and people I care about is to get the update, and for people who are high risk, definitely get the update."
Al-Aly offered a similarly direct assessment regarding heart health, particularly for older adults and those with comorbidities: "Forgoing vaccinations, that's leaving a lot of protection on the table."