Sex-specific associations between lifetime diagnosis of bipolar disorder and cardiovascular disease: A cross-sectional analysis of 257,673 participants from the UK Biobank

Background: Sex is seldom considered as a potential moderator of the impact of bipolar disorder (BD) on car-diovascular disease (CVD) risk. We aimed to characterize the sex-specific association of CVD and BD using data from the UK Biobank.Methods: In a cross-sectional analysis, we compared the odds ratio between women and men with BD for seven CVD diagnoses (coronary artery disease, myocardial infarction, angina, atrial fibrillation, heart failure, stroke, and essential hypertension) and four cardiovascular biomarkers (arterial stiffness index, low-density lipoprotein, C-reactive protein, and HbA1c) in 293 participants with BD and 257,380 psychiatrically healthy controls in the UK Biobank.Results: After adjusting for age, we found a two-to three-fold stronger association among women than among men between BD and rates of coronary artery disease, heart failure, and essential hypertension, with a significant sex-by-diagnosis interactions. The association remained significant after controlling for self-reported race, edu-cation, income, and smoking status. After controlling for potential confounders, there was no significant asso-ciation between sex and any cardiovascular biomarkers.Limitations: These analyses could not disentangle effects of BD from its treatment.Conclusions: Our results underscore the importance of incorporating sex and mental illness in risk estimation tools for CVD, and improving screening for, and timely treatment of, CVD in those with BD. Future research is needed to better understand the contributors and mechanisms of sex differences related to CVD risk in BD.