Glucocorticoid-Induced Cushing Syndrome Linked to Increased Risk for CV Events

Objective:

To investigate whether there is an increased risk of cardiovascular events in people who exhibit iatrogenic Cushing’s syndrome during treatment with glucocorticoids.

Design:

Cohort study.

Setting:

424 UK general practices contributing to The Health Improvement Network database.

Participants:

People prescribed systemic glucocorticoids and with a diagnosis of iatrogenic Cushing’s syndrome (n=547) and two comparison groups: those prescribed glucocorticoids and with no diagnosis of iatrogenic Cushing’s syndrome (n=3231) and those not prescribed systemic glucocorticoids (n=3282).

Main outcome measures:

Incidence of cardiovascular events within a year after diagnosis of iatrogenic Cushing’s syndrome or after a randomly selected date, and association between iatrogenic Cushing’s syndrome and risk of cardiovascular events.

Results:

417 cardiovascular events occurred in 341 patients. Taking into account only the first event by patient (coronary heart disease n=177, heart failure n=101, ischaemic stroke n=63), the incidence rates of cardiovascular events per 100 person years at risk were 15.1 (95% confidence interval 11.8 to 18.4) in those prescribed glucocorticoids and with a diagnosis of iatrogenic Cushing’s syndrome, 6.4 (5.5 to 7.3) in those prescribed glucocorticoids without a diagnosis of iatrogenic Cushing’s syndrome, and 4.1 (3.4 to 4.8) in those not prescribed glucocorticoids. In multivariate analyses adjusted for sex, age, intensity of glucocorticoid use, underlying disease, smoking status, and use of aspirin, diabetes drugs, antihypertensive drugs, lipid lowering drugs, or oral anticoagulant drugs, the relation between iatrogenic Cushing’s syndrome and cardiovascular events was strong (adjusted hazard ratios 2.27 (95% confidence interval 1.48 to 3.47) for coronary heart disease, 3.77 (2.41 to 5.90) for heart failure, and 2.23 (0.96 to 5.17) for ischaemic cerebrovascular events). The adjusted hazard ratio for any cardiovascular event was 4.16 (2.98 to 5.82) when the group prescribed glucocorticoids and with iatrogenic Cushing’s syndrome was compared with the group not prescribed glucocorticoids.

Conclusion:

People who use glucocorticoids and exhibit iatrogenic Cushing’s syndrome should be aggressively targeted for early screening and management of cardiovascular risk factors.

In adjusted analyses, the rate of cardiovascular events per 100 person-years was 15.1 among patients with Cushing syndrome, 6.4 among glucocorticoid users without Cushing syndrome, and 4.1 among nonusers.

BMJ 2012;345:e4928