UC San Diego

Background: Cardiovascular disease (CVD) is the number one cause of death in the United States and around the world. Syphilis is a sexually transmitted infection conferred by the spirochete Treponema pallidum which demonstrates a unique affinity for the human CV system. It is understood that Treponemal invasion of vascular and cardiac tissue, in the absence of treatment, may result in the CV manifestations of late, tertiary syphilis including: aortic aneurysm, aortic insufficiency, coronary artery disease (CAD), and stroke. Recent literature has suggested that chronic kidney disease (CKD) may also be among these sequalae. It is the current understanding that syphilitic CVD morbidity is effectively prevented and treated with the standard of care (SOC) antimicrobial therapy dictated for early and late syphilis, however, there is a relative paucity of data to support this. In light of the ongoing syphilis epidemic in the United States, our group sought to revisit and evaluate these central tenets of syphilis care. Methods: A preliminary, 10-year retrospective analysis (01/2013-12/31/2022) of deidentified electronic medical records (EMR) from a California-based academic health system was undertaken. The study population consisted of all health system patients >18 who were seen during the study period. The exposure of interest consisted of ICD-10 codes representative of syphilis infection with CVD outcomes defined as ICD-10 diagnoses reflective of the known, principle clinical manifestations of tertiary syphilis as well as CKD and HTN. Unadjusted, bivariate analysis was performed for preliminary assessment of exposure-outcome association. Results: 3,559,370 unique EMR were included in final analysis. 5,915 patients were found to have a diagnosis of syphilis. The majority of patients diagnosed with syphilis had documentation of treatment. Patients with history of syphilis infection had significantly higher odds of aortic aneurysm (OR = 6.17; 95%CI = 5.07-7.5), CAD (OR = 5.81; 95%CI = 5.37-6.27), aortic insufficiency (OR = 5.52; 95%CI = 4.47-6.81), stroke (OR = 5; 95%CI = 4.58-5.46), HTN (OR = 8.38; 95%CI = 7.94-8.85), and CKD (OR = 10.94; 95%CI = 10.28-11.64) relative to uninfected patients. Conclusion: Preliminary analysis indicates syphilis infection to be associated with significantly increased odds of CVD morbidity across all outcomes measured including CKD. These data suggest that the CV impact of syphilis may be broader than previously understood and raise concern for a clinically significant limitation to the current SOC in protection against CVD morbidity. A follow-up study is underway which will utilize multivariate logistic regression analysis to determine the independent effect of syphilis infection adjusting for multiple confounders to further clarify our preliminary results.