Sex-Specific Risk of Cardiovascular Disease in Autoimmune Addison Disease—A Population-Based Cohort Study

CONTEXT: Little is known of cardiovascular disease (CVD) in autoimmune Addison disease (AAD). Inadequate glucocorticoid replacement might potentially increase CVD risk. OBJECTIVE: To examine CVD in AAD in subgroups of ischemic heart disease (IHD) and cerebrovascular disease (CeVD) and investigate the effects of glucocorticoid and mineralocorticoid dosing. DESIGN, SETTING, AND PATIENTS: In this cohort-control study, we used Swedish health registries from 1964 to 2013 to identify 1500 subjects with AAD and 13,758 matched controls. Incident CVD was analyzed from 2006 to 2013. Adjusted hazard ratios (aHRs) were calculated using Cox proportional hazard models. Glucocorticoid and mineralocorticoid doses were stratified to examine dose-related risks. RESULTS: During 8807 person-years (PY), 94 events of first CVD (10.7/1000 PY) in patients with AAD occurred compared with 563 events during 80,163 PY (7.0/1000 PY) in controls. IHD was significantly more common in women (aHR, 2.15; 95% CI, 1.49 to 3.10) but not men (aHR, 1.16; 95% CI, 0.75 to 1.78) with AAD compared with controls. No increase in CeVD risk was detected (aHR, 0.88; 95% CI, 0.56 to 1.37, women; aHR, 0.88; 95% CI 0.53 to 1.50, men). CVD was associated with greater glucocorticoid and mineralocorticoid replacement doses in women but not men. CONCLUSION: The risk of IHD but not CeVD is increased in AAD, especially in women. The risk of CVD independently correlated with greater glucocorticoid and mineralocorticoid replacement doses in women. Our data suggest that close monitoring and early treatment of risk factors for CVD, among women in particular, might be warranted.