Patients with adrenal insufficiency may have higher rates of cardiovascular events due to the presence of cardiovascular comorbidities, shows a study published in The Journal of Clinical Endocrinology and Metabolism.
Led by Kanchana Ngaosuwan, MD, PhD, of Imperial College London, UK, the authors of this population-based matched cohort study also found that cerebrovascular events were independently increased in patients with secondary adrenal insufficiency, particularly in those treated with irradiation therapy. Cardiovascular mortality, specifically from ischemic heart disease, was higher regardless of having secondary adrenal insufficiency or primary adrenal insufficiency (Addison’s disease).
Adrenal insufficiency occurs when the adrenal glands fail to produce adequate glucocorticoids. In Addison’s disease, it arises from the adrenal glands, but in secondary adrenal insufficiency, it occurs as a result of a pituitary or hypothalamic condition. Glucocorticoid replacement therapy is usually the first line of defense, but the treatment is associated with a number of adverse events, such as cardiovascular disease. Ischemic heart disease is the leading cause of death for patients with Addison’s disease.
Data from this study was sourced from the Clinical Practice Research Datalink which collected information from 15,354,125 individuals living in the United Kingdom between 1987 and 2017. Data from patients prescribed glucocorticoid prescriptions for adrenal insufficiency (primary: n=2,052; secondary: n=3,948) and random age and gender matched controls (primary: n=20,366; secondary: n=39,134) were assessed for comorbidities and clinical outcomes.
Patients and controls had previous cardiovascular disease (17.5% vs 11.2%), diabetes (10.4% vs 4.8%), hypertension (22.1% vs 13.6%), dyslipidemia (20.5% vs 5.0%), and 19.6% and 4.9% of patients and controls were taking statins, respectively.
Composite cardiovascular events occurred at a rate of 31.4 (95% CI, 29.6-33.3) per 1,000 person-years among the patients and 24.4 (95% CI, 23.9-24.9; P <.0001) per 1,000 person years among the controls. Stratified by adrenal insufficiency subtype, after correcting for cofounders, patients with primary (adjusted hazard ratio [aHR], 1.08; 95% CI, 0.96-1.22) and secondary (aHR, 1.10; 95% CI, 1.01-1.19) adrenal insufficiency were at marginally increased risk for composite cardiovascular events.
Cerebrovascular disease occurred at a rate of 10.4 (95% CI, 9.5-11.5) per 1.000 person years among the patients and 7.2 (95% CI, 7.0-7.5; P <.0001) per 1,000 person years among the controls. Only patients with secondary adrenal insufficiency were at increased risk for cerebrovascular disease (aHR, 1.53; 95% CI, 1.34-1.74).
All patients had increased risk for hospitalization due to cardiovascular diseases (aHR, 1.41; 95% CI, 1.28-1.55) and only the patients with secondary adrenal insufficiency were more likely to be hospitalized with cerebrovascular disease (aHR, 1.63; 95% CI, 1.28-2.08).
Patients had increased rates of cardiovascular mortality compared with controls (9.9 vs 6.4 per 1,000 person years; P <.0001). Both patients with primary (aHR, 1.58; 95% CI, 1.19-2.10) and secondary (aHR, 1.23; 95% CI, 0.99-1.52) insufficiency were at increased risk for cardiovascular mortality. Risk for cerebrovascular mortality was elevated for patients with secondary insufficiency (aHR, 1.14; 95% CI, 0.78-1.67).
Stratified by secondary insufficiency, age, and sex, women (aHR, 1.18; 95% CI, 1.04-1.31; P =.016) and patients who were less than 50 years old (aHR, 1.58; 95% CI, 1.22-2.03; P <.0001) were at increased risk for composite cardiovascular events. Similarly, patients 50 years old or younger were at increased risk for cerebrovascular disease (aHR, 3.67; 95% CI, 2.60-5.17; P <.0001).
These data may be limited by the cohort imbalance of disease risk factors, although the investigators corrected for these features, some residual biases may remain.
While further study is needed to assess changes in treatment approaches, the authors suggested that “these findings support further optimization of glucocorticoid replacement in conjunction with cardio protective interventions in patients with adrenal insufficiency.”
Ngaosuwan K, Johnston D G, Godsland I F, et al. Cardiovascular disease in patients with primary and secondary adrenal insufficiency and the role of comorbidities. J Clin Endocrinol Metab. 2021;dgab063. doi:10.1210/clinem/dgab063.