AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Association Between Syphilis and Risk of Cardiovascular Disease: A Propensity-Matched Real-World Analysis of 107,258 Adults Over 3 Years
By Jaiswal A, Jaiswal V, Nain P
BACKGROUND: Syphilis, caused by Treponema pallidum, is a systemic sexually transmitted infection with rising incidence. Beyond neurological manifestations, syphilis may confer sustained cardiovascular risk through endothelial injury, vasculitis, and chronic immune dysregulation. OBJECTIVES: To evaluate whether syphilis is independently associated with increased 3-year risk of all-cause mortality (ACM), ischemic stroke, hemorrhagic stroke, transient ischemic attack (TIA), acute myocardial infarction (AMI), heart failure (HF), cardiac arrhythmias, pulmonary embolism (PE), and peripheral artery disease (PAD) compared with propensity-matched controls. METHODS: This retrospective cohort study used the TriNetX Global Collaborative Network (172 healthcare organizations). Adults (≥18 years) with a syphilis diagnosis (ICD-10: A51-A53) between January 2010 and January 2021, without prior cardiovascular disease or HIV, comprised Cohort 1; controls were adults with routine health encounters and no syphilis or cardiovascular history (Cohort 2). Propensity score matching (1:1) was performed on age, sex, diabetes, hypertension, hyperlipidemia, ischemic heart disease, CKD, COPD, BMI, LVEF, and eGFR. Outcomes were assessed over a 3-year follow-up window using Kaplan-Meier survival analysis with hazard ratios (HR), 95% confidence intervals (CI), and log-rank testing. RESULTS: The total matched sample comprised 107,258 patients (53,629 per cohort). Mean age was 44.0 ± 18.7 years; 55.9% were male. Over 3 years, syphilis was associated with significantly higher risk of ischemic stroke (HR 3.27, 95% CI 2.88-3.72; p<0.001), hemorrhagic stroke (HR 1.46, 95% CI 1.23-1.72; p<0.001), ACM (HR 1.36, 95% CI 1.26-1.47; p<0.001), HF (HR 1.28, 95% CI 1.07-1.54; p=0.008), and TIA (HR 1.22, 95% CI 1.00-1.48; log-rank p=0.048). No significant differences were observed for AMI (HR 1.16, 95% CI 0.98-1.38; p=0.077), PE (HR 0.92, 95% CI 0.78-1.09; p=0.341), or PAD (HR 1.08, 95% CI 0.84-1.40; p=0.539). CONCLUSIONS: In a large propensity-matched real-world cohort followed over 3 years, syphilis was independently associated with a 3-fold increased risk of ischemic stroke, 46% higher risk of hemorrhagic stroke, 36% higher all-cause mortality, and significantly elevated HF and TIA risk.