Introduction and Objective
Cardiovascular disease (CVD) remains a leading cause of death in women. The Atherosclerotic Cardiovascular Disease 10-year risk score recommended by the American College of Cardiology does not encompass chronic inflammatory diseases, which is associated with increased CVD risk. This score may underestimate risk particularly in women with autoimmune liver diseases (AILD) such as autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). We investigated if women with AILD are at increased CVD risk compared to female and male controls.

Methods
Using TriNetX, we conducted a multi-center, retrospective cohort study of patients with AIH, PBC, and PSC from Jan 1999 to Jan 2019. Study cohorts were female with respective AILD who also had diabetes mellitus (DM), hypertension (HTN), and hyperlipidemia (HLD). Control cohorts were either female or male with DM, HTN, and HLD. AILD, biologics, immune modulators, and steroids were explicitly excluded from controls. Female study versus female control cohort were 1:1 propensity-score matched (PSM) for age, race, ethnicity, ASCVD risk factors, and tobacco use. Female study versus male control cohort were PSM for age, race, ethnicity, and tobacco use. Statins were controlled for if control cohort had significantly greater usage. The primary outcome was summative cardiovascular (CV) risk including unstable angina, acute myocardial infarction, presence of coronary angioplasty implant, coronary artery bypass, percutaneous coronary intervention, and cerebral infarction. The incidence of CV risk was calculated via risk difference through TriNetX.

Results
Females with AIH had significantly greater CV risk compared to females without AIH (24.7% vs. 18.9%, P-value<0.0001). Females with PBC had significantly greater CV risk compared to females without PBC (24.9% vs. 18.4%, P-value<0.0001). There was no significant difference in CV risk between females with and without PSC (26.4% vs. 20.7%, P-value=0.26).

When comparing to men without disease, females with AIH did not have significant CV risk (24.7% vs. 22.4%, P-value=0.10). Similarly, there was no significant difference in CV risk between females with PBC and males without PBC (24.9% vs. 23.9%, P-value=0.53). There was also no significant difference between females with PSC compared to males without PSC (26.2% vs. 17.7%, P-value=0.08).

Conclusion
In this study, females with AIH and PBC lose CV protection conferred by female sex. There is no difference in CV risk in females with AILD compared to males without respective diseases. As gastroenterologists and hepatologists, there exists a potential oversight in our risk stratification approach to females with chronic AILD. In this distinct clinical context, enhancing risk assessment strategies is imperative for optimizing patient outcomes.

Joy Zhao

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