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Addison’s disease raises ischemic heart disease risk in women

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January 8, 2019

Swedish women with Addison’s disease are more likely to develop ischemic heart disease than healthy adults or men with the condition, whereas both men and women with the disease were more likely to die of a coronary event vs. healthy controls, study data show.

“Studies comparing cardiovascular risk factors in cohorts of patients with adrenal insufficiency of predominantly autoimmune etiology, and adequately matched controls, are rare,” Jakob Skov, a doctoral student in the department of molecular medicine and surgery at the Karolinska Institutet in Stockholm, and colleagues wrote in the study background. “To our knowledge, they have all evaluated multiple risk factors (measured or treated for) such as dyslipidemia, body mass index, abdominal adiposity, glucose metabolism or hypertension. While results generally indicate unfavorable metabolic profiles in [autoimmune Addison’s disease], they do so in an inconsistent manner.”

Skov and colleagues analyzed data from 1,500 patients with Addison’s disease and 13,785 matched controls, using data from the Swedish National Patient Register, the Swedish Prescribed Drug Register and the Cause of Death Register collected between 1964 and 2013, and assessed incident CVD (nonfatal and fatal events) between 2006 and 2013. Researchers estimated mean daily doses of hydrocortisone and fludrocortisone and stratified hydrocortisone doses by tertiles of low, medium and high and fludrocortisone doses by low and high to evaluate dose-related risks. Researchers used Cox proportional hazard models to estimate HRs for CVD, ischemic heart disease and cerebrovascular disease, adjusting for diabetes and chronic obstructive pulmonary disease.

During 8,807 person-years, researchers observed 94 initial CVD events in patients with Addison’s disease vs. 563 first CVD events during 80,163 person-years in matched controls, corresponding to an HR of 1.2 (95% CI, 0.95-1.51) after adjustment for diabetes and chronic obstructive pulmonary disease. Patients with Addison’s disease were more likely to develop ischemic heart disease vs. controls (adjusted HR = 1.61; 95% CI, 1.22-2.12); however, there were no between-group differences for cerebrovascular disease.

When stratified by sex, researchers found that women with Addison’s disease were twice as likely as men to develop ischemic heart disease, with adjusted HRs of 2.15 (95% CI, 1.49-3.1) vs. 1.16 (95% CI, 0.75-1.78). There were no sex-specific effects observed for cerebrovascular disease.

In examining glucocorticoid dose-related risks, researchers found that higher doses of hydrocortisone and fludrocortisone were associated with an incremental increase in CVD events in men and women, although CIs were wide, and the association rose to significance only in women prescribed high doses.

Among patients with Addison’s disease, 29 of 71 ischemic heart disease events (40.8%) were fatal, whereas 96 of 338 ischemic heart disease events (28.4%) were fatal among controls (P = .04 for difference).

“We believe that the added data of this study calls for recommendations of prescribing the lowest glucocorticoid and mineralocorticoid doses sufficient for well-being, and for closer monitoring of risk factors for CVD, especially in women,” the researchers wrote. – by Regina Schaffer

Disclosures: The authors report no relevant financial disclosures.

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