Syphilis infection was associated with higher risks of several major cardiovascular outcomes in patients without preexisting cardiovascular disease, according to a retrospective cohort study published in JAMA Network Open.
Researchers evaluated 8,814 patients (mean age, 50 years; 54% female), including 1,469 patients with syphilis matched 5:1 to 7,345 controls on age, sex, body mass index, and comorbidities. The study spanned January 2011 to July 2025 and was conducted within a tertiary health care system in New Orleans, Louisiana.
Patients with syphilis experienced higher rates of multiple cardiovascular events compared with controls, including myocardial infarction (7% vs 4%), ischemic stroke (10% vs 6%), hemorrhagic stroke (2% vs 1%), aortic aneurysm or dissection (3% vs 1%), and peripheral artery disease (6% vs 4%).
After multivariable adjustment, syphilis remained independently associated with increased risk of aortic aneurysm or dissection, ischemic and hemorrhagic stroke, myocardial infarction, peripheral artery disease, and death. Mortality risk was markedly elevated (hazard ratio, 5.80; 95% confidence interval, 3.81–8.82), although the investigators cautioned that residual confounding likely contributed to the magnitude of this association. No statistically significant differences were observed for heart failure, atrial fibrillation, aortic regurgitation, or venous thromboembolism.
Subgroup analyses suggested that cardiovascular risk varied by disease stage. No associations were observed in primary or secondary syphilis, although event rates were limited. In contrast, tertiary syphilis was associated with increased risk across multiple outcomes, including aortic disease, ischemic stroke, myocardial infarction, and mortality. Late latent syphilis was also associated with increased risks of mortality, aortic disease, and ischemic stroke.
In a post hoc analysis of patients with human immunodeficiency virus infection, most cardiovascular associations were not statistically significant, although mortality remained elevated among patients with syphilis.
The study was conducted in Louisiana, where syphilis incidence is among the highest in the US; the cohort rate was 101 cases per 100,000, consistent with the reported state-level rate.
The researchers noted several limitations, including the retrospective design, potential residual confounding, reliance on diagnostic codes, and lack of data on treatment status or laboratory measures.
“[S]yphilis was independently associated with increased risk of several adverse cardiovascular outcomes, particularly those involving vascular tissue, such as [aortic aneurysm or dissection], ischemic and hemorrhagic stroke, peripheral artery disease, and myocardial infarction,” wrote lead study author Eli Tsakiris, BS, of Tulane Research Innovation for Arrhythmia Discovery in Louisiana, and colleagues, who emphasized the importance of early detection and treatment and suggested a potential role for incorporating cardiovascular risk assessment into syphilis management.
Dr Nassir F. Marrouche reported receiving grant support from Abbott Laboratories, Biosense Webster, and Siemens AG, personal fees from Medtronic plc, Boston Scientific Corporation, and Preventice Inc, and holding equity in Cardiac Design Labs. Dr Amitabh C. Pandey reported advisory board participation with Novartis AG. No other disclosures were reported.
Source: JAMA Network Open
