US adults diagnosed as having late-stage syphilis are at higher risk for major cardiovascular conditions such as stroke and heart attack, as well as death, than those without the infection, per a study published this week in JAMA Network Open.

Researchers from Tulane University and the Southeast Louisiana Veterans Health Care System used hospital electronic health records to retrospectively assess whether syphilis infection is independently tied to an increased risk of adverse cardiovascular outcomes in adults served by a New Orleans health care system from January 2011 to July 2025.

Participants included 1,469 patients with any stage of syphilis and 7,345 uninfected controls matched on demographic factors and underlying illnesses. The average participant age was 50 years, and 53.9% were women.

Assessed outcomes were heart attack, heart failure (HF), aortic regurgitation (AR; heart valve disease), atrial fibrillation (AF), aortic aneurysm (AA) or dissection (AD), ischemic stroke, hemorrhagic stroke, peripheral artery disease (PAD), venous thromboembolism (VTE), and death.

“To date, no US cohort studies, to our knowledge, have used matched controls to evaluate the independent association between syphilis and incident cardiovascular outcomes, resulting in a critical gap in this patient population,” the investigators wrote. “With syphilis resurging across the US and an increase of more than 50% in reported cases from 2018 to 2023, an investigation of the potential morbid effects of syphilis is important.”

Nearly 6 times higher risk of death

Heart attack occurred in 6.9% of syphilis patients, compared with 4.2% of controls, while ischemic stroke was documented in 10.3% and 5.7%, respectively. Hemorrhagic stroke was also more common in syphilis patients (2.0% vs 0.8%). 

With syphilis resurging across the US and an increase of more than 50% in reported cases from 2018 to 2023, an investigation of the potential morbid effects of syphilis is important.

Vascular complications such as AA or AD occurred in 3.3% of syphilis patients, compared with 1.3% of controls, and 62% of syphilis patients developed PAD, versus 4.1% of controls. AR was also more common in the syphilis group (1.0% vs 0.5%). Rates of HF (11.2% vs 9.6%), VTE (0.8% vs 0.4%), and AF (5.4% in both groups) weren’t significantly different.  

Adjusted analyses linked syphilis with an increased risk of AA or AD (hazard ratio [HR], 2.08), ischemic stroke (HR, 1.53), hemorrhagic stroke (HR, 1.92), PAD (HR, 1.28), death (HR, 5.80), and heart attack (HR, 1.33). No associations were found for HF (HR, 0.98), atrial fibrillation (HR, 0.85), AR (HR, 1.58), or VTE (HR, 1.47).

No associations were noted between primary or secondary syphilis and any primary cardiovascular outcome. In contrast, tertiary syphilis—the final, latest stage of the disease—showed higher rates of death (HR, 6.93), AA or AD (HR, 5.57), ischemic stroke (HR, 3.23), hemorrhagic stroke (HR, 2.62), MI (HR, 2.15), PAD (HR, 2.45), HF (HR, 2.01), and AF (HR, 2.19). Rates of AR (HR, 2.20) and VTE (HR, 0.84) didn’t show statistically significant increases.

In patients with latent syphilis (an absence of symptoms), diagnoses of early latent syphilis occurred less often and demonstrated no links to any evaluated outcome, with several outcomes not estimable due to too few events. But patients with late latent syphilis had significantly higher rates of death (HR, 4.08), AA or AD (HR, 2.41), and ischemic stroke (HR, 1.82). No associations were noted for hemorrhagic stroke, MI, PAD, HF, AF, VTE, or AR.

11-fold greater odds of death with dual syphilis-HIV

A post hoc subgroup analysis of syphilis patients who also had HIV compared with a control cohort with HIV showed that syphilis wasn’t tied to a significantly increased risk of most cardiovascular outcomes after matching. 

What we’ve shown here is that with syphilis, these manifestations of cardiovascular disease may be overlooked currently, but they should not be ignored.

HRs for AA or AD (0.75), hemorrhagic stroke (0.95), ischemic stroke (1.06), heart attack (0.99), PAD (0.97), HF (0.93), AF (0.81), VTE (1.24), and AR (1.51) didn’t show a statistically significant increase. In contrast, all-cause death rates stayed significantly elevated among patients with both syphilis and HIV (HR, 11.32).

“Given the rising incidence of syphilis both locally and nationally, these findings underscore the importance of early detection and treatment,” the authors wrote. “Further research is needed to understand whether prompt antibiotic therapy mitigates long-term cardiovascular risk and to identify the best screening practices in patients most vulnerable to cardiovascular complications.”

In a Tulane University news release, corresponding author Amitabh Pandey, MD, of Tulane, called the research an early step toward understanding how infectious diseases such as syphilis may increase cardiovascular risk, perhaps through chronic inflammation.

“We know that syphilis can increase systemic inflammation,” he said. “This is important as it is known that inflammation can really kick start and accelerate processes that push cardiovascular disease into overdrive.”

“What we’ve shown here is that with syphilis, these manifestations of cardiovascular disease may be overlooked currently, but they should not be ignored,” he added. “Especially because they can outlast even the treatment of the syphilis and still contribute to cardiovascular disease.”