Adverse Cardiovascular Outcomes in Patients With Syphilis

Importance: Syphilis, which is caused by Treponema pallidum, has historically been associated with cardiovascular complications. Despite a resurgence of syphilis incidence in the US, large-scale studies evaluating its independent cardiovascular impact are lacking. Objective: To determine whether syphilis infection is independently associated with increased risk of adverse cardiovascular outcomes in a US health system population. Design, Setting, and Participants: This retrospective cohort study with a 15-year follow-up (January 1, 2011, to July 1, 2025) was performed within a tertiary health care system in New Orleans, Louisiana. Participants included adults with syphilis identified using codes from the International and Statistical Classification of Diseases, Tenth Revision (ICD-10) and controls without syphilis who were matched based on demographic characteristics and comorbidities. Patients with preexisting cardiovascular disease were excluded. Data were analyzed from January 1, 2011, to July 1, 2025. Exposures: Diagnosis of syphilis (primary, secondary, tertiary, or unspecified stage) documented by ICD-10 codes. Main Outcomes and Measures: Incident cardiovascular events 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 assessed using Kaplan-Meier survival curves and were adjusted for body mass index. Results: A total of 8814 participants were included in the analysis (4753 [53.9%] female; mean [SD] age, 50.0 [17.0] years). The syphilis group (n = 1469) and control group (n = 7345) were similar in terms of their demographic characteristics (mean [SD] age, 50.1 [17.0] vs 50.0 [17.6] years [P = .78]; 795 [54.1%] vs 3958 [53.9%] female [P = .84]) and comorbidities. In adjusted analyses, syphilis was associated with an increased risk of aortic aneurysm or dissection (hazard ratio [HR], 2.08; 95% CI, 1.47-2.94; P = .001), ischemic stroke (HR, 1.53; 95% CI, 1.27-1.84; P < .001), hemorrhagic stroke (HR, 1.92; 95% CI, 1.23-2.99; P = .004), peripheral artery disease (HR, 1.28; 95% CI, 1.01-1.62; P = .04), death (HR, 5.80; 95% CI, 3.81-8.82; P < .001), and myocardial infarction (HR, 1.33; 95% CI, 1.06-1.67; P = .01). No associations were found for heart failure (HR, 0.98; 95% CI, 0.83-1.17), atrial fibrillation (HR, 0.85; 95% CI, 0.67-1.08), aortic regurgitation (HR, 1.58; 95% CI, 0.87-2.87), or venous thromboembolism (HR, 1.47; 95% CI, 0.76-2.94). Conclusions and Relevance: In this retrospective cohort study of adults with syphilis, infection was independently associated with higher risk of several major cardiovascular outcomes. These findings underscore the importance of early detection and treatment of syphilis and suggest a role for incorporating cardiovascular risk assessment into comprehensive syphilis management strategies.