As syphilis cases rise, study links infection with higher risk of stroke, heart attack and other serious cardiovascular problems

Syphilis has been rising sharply in the United States, with especially high rates in Southern states. Now, a new study from Tulane University researchers suggests the long-term infection may carry another risk that is often overlooked: serious damage to the heart and blood vessels.

The study, published in JAMA Network Open, found that adults with later-stage syphilis were more likely to develop major cardiovascular problems - including stroke, heart attack or aortic aneurysm - than similar patients without the infection. The increased risk was primarily found in those whose infection progressed longer than a year.

The findings are significant, the researchers said, because syphilis may be seen as an infection that can be cured and forgotten. Existing antibiotic treatment is largely effective and sometimes a single shot of penicillin is enough to eradicate the disease. However, this study suggests that long-term, untreated syphilis could carry an additional - and potentially life-threatening - risk of associated cardiovascular issues patients may not be aware of.

"This is one of the few modern large population studies to find that syphilis can be associated with catastrophic cardiovascular and neurologic effects," said lead author Eli Tsakiris, a medical student at Tulane University School of Medicine. "Cardiovascular disease is the leading cause of death in the U.S. and with syphilis cases rising recently, this association is something that all providers treating high-risk patients need to be aware of."

Syphilis, a sexually transmitted infection caused by the bacterium Treponema palliduma, surged in recent years with the U.S. seeing an 80% rise in cases from 2018-2022, according to the Centers for Disease Control and Prevention.

To conduct the study, researchers reviewed electronic health records from three New Orleans hospitals in a single health system over 15 years beginning in 2011. They compared 1,469 adults with syphilis with 7,345 people without syphilis. To better isolate the relationship, they excluded patients who already had cardiovascular disease before the study period.

After adjustment, the researchers found that patients with syphilis had about twice the risk of aortic aneurysm or dissection, a 53% higher risk of ischemic stroke, a 92% higher risk of hemorrhagic stroke, a 31% higher risk of heart attack and a 28% higher risk of peripheral artery disease. The study also found a much higher risk of death.

This study is the first in the U.S. to find a link between syphilis and peripheral artery disease, a condition where blood flow away from the heart is reduced, causing cramping, numbness and slow-healing wounds.

The study did not find significant differences in heart failure, atrial fibrillation or other outcomes. Because it was a retrospective study, the findings indicate an association between syphilis and cardiovascular problems but cannot prove cause-and-effect relationship.

Corresponding author Dr. Amitabh C. Pandey, director of Cardiovascular Translational Research at Tulane University School of Medicine, said the work is an early step toward understanding how infectious diseases such as syphilis may add to cardiovascular risk, potentially through chronic inflammation.

The findings suggest these problems may be more common than many clinicians realize. Going forward, Pandey and his team said more work is needed to understand mechanistically if syphilis treatment can lower cardiovascular risk.

"We know that syphilis can increase systemic inflammation. This is important as it is known that inflammation can really kick start and accelerate processes that push cardiovascular disease into overdrive," Pandey said. "What we've shown here is that with syphilis, these manifestations of cardiovascular disease may be overlooked currently, but they should not be ignored. Especially because they can outlast even the treatment of the syphilis and still contribute to cardiovascular disease."