Syphilis has long been linked to cardiovascular complications, yet its independent association with contemporary cardiovascular outcomes remains uncertain. A retrospective cohort study published in JAMA Network Open evaluated the relationship between syphilis infection and incident cardiovascular events over extended follow-up in a US health system population.

The analysis included 8,814 adults without preexisting cardiovascular disease, identified between January 2011 and July 2025 within a tertiary care system. Patients with syphilis were identified using International Classification of Diseases, Tenth Revision (ICD-10) codes and were matched with controls without syphilis based on demographic characteristics and comorbidities. The exposure included all stages of syphilis. 

Cardiovascular outcomes included myocardial infarction, heart failure, aortic regurgitation, atrial fibrillation, aortic aneurysm or dissection, ischemic stroke, hemorrhagic stroke, peripheral artery disease, venous thromboembolism, and death. Outcomes were evaluated using time-to-event analyses, adjusted for body mass index.

The cohort included 1,469 patients with syphilis and 7,345 matched controls, with similar baseline characteristics. Over follow-up, syphilis was associated with higher risk of aortic aneurysm or dissection (hazard ratio [HR] 2.08, 95% CI 1.47-2.94; P=0.001), ischemic stroke (HR 1.53, 95% CI 1.27-1.84; P<0.001), hemorrhagic stroke (HR 1.92, 95% CI 1.23-2.99; P=0.004), peripheral artery disease (HR 1.28, 95% CI 1.01-1.62; P=0.04), myocardial infarction (HR 1.33, 95% CI 1.06-1.67; P=0.01), and death (HR 5.80, 95% CI 3.81-8.82; P<0.001). No associations were observed for heart failure, atrial fibrillation, aortic regurgitation, or venous thromboembolism.

Syphilis was associated with a higher risk of several cardiovascular outcomes, although associations were not consistent across all endpoints.