Syphilis as an Independent Risk Factor for Aortic Aneurysm and Stroke

Article Impact Level: HIGH
Data Quality: STRONG
Summary of  JAMA Network Open https://doi.org/10.1001/jamanetworkopen.2026.6771
Dr. Eli Tsakiris et al.

Points

Investigators conducted a large population study comparing over one thousand patients with syphilis to seven thousand controls to evaluate the long-term impact of the infection on major cardiovascular health outcomes.
The findings revealed that patients with syphilis have twice the risk of developing aortic aneurysms and nearly double the risk of suffering a hemorrhagic stroke compared to uninfected individuals.
Clinical data indicated a fifty-three percent higher risk of ischemic stroke and a thirty-one percent increase in heart attacks particularly among those whose infection had progressed for over a year.
This research represents the first American study to establish a significant clinical link between syphilis and peripheral artery disease which causes reduced blood flow and slow healing wounds in patients.
These results suggest that the chronic systemic inflammation caused by syphilis can accelerate cardiovascular disease and underscores the urgent need for early detection and comprehensive heart health monitoring for all patients.

Summary

This study evaluated the longitudinal association between syphilis infection and major adverse cardiovascular outcomes using a retrospective cohort of 1,469 adults matched with 7,345 controls. Given the 80% surge in syphilis cases between 2018 and 2022, the research sought to determine if chronic infection acts as an independent driver of vascular pathology. By reviewing electronic health records over a 15-year period and excluding patients with pre-existing cardiovascular disease, investigators isolated the impact of Treponema pallidum on arterial health, specifically focusing on those with infections progressing beyond one year.

The analysis revealed that syphilis is independently associated with a significantly elevated risk of catastrophic cardiovascular events. After adjustment, patients with syphilis exhibited a 100% higher risk of aortic aneurysm or dissection and a 92% higher risk of hemorrhagic stroke. Furthermore, the cohort demonstrated a 53% higher risk of ischemic stroke, a 31% higher risk of myocardial infarction, and a 28% higher risk of peripheral artery disease. These findings represent the first U.S. evidence linking syphilis to peripheral artery disease, though no significant associations were found for heart failure or atrial fibrillation.

The results suggest that systemic inflammation secondary to chronic syphilis may accelerate atherosclerosis and vascular degradation, even after antibiotic eradication. Hazard ratios were consistently greatest in patients with late-stage syphilis, underscoring the necessity of early detection to mitigate long-term mortality. These data support the integration of comprehensive cardiovascular risk assessment into syphilis management strategies. Future prospective work is required to determine the precise biological mechanisms of this association and to evaluate whether standard syphilis treatments can effectively attenuate the observed rise in major cardiovascular events.

Link to the article: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2847672

References

Tsakiris, E., Feng, H., Bidaoui, G., Massad, C., Zha, J., Wu, Z., Jia, Y., Liu, Y., Younes, H., Menassa, Y., Abou Khalil, M., Bsoul, M., Atasi, M. M., Zakhour, S., Mushatt, D., Kreidieh, O., Marrouche, N. F., & Pandey, A. C. (2026). Adverse cardiovascular outcomes in patients with syphilis. JAMA Network Open, 9(4), e266771. https://doi.org/10.1001/jamanetworkopen.2026.6771