Markers of atherosclerosis in patients with Cushing's syndrome: a meta-analysis of literature studies

Background: Several studies reported an increased cardiovascular (CV) risk in Cushing's syndrome (CS). We performed a meta-analysis on the impact of CS on major markers of atherosclerosis. Methods: Studies on intima-media thickness (IMT), carotid plaques prevalence, and flow-mediated dilation (FMD) in CS patients and controls were searched in the PubMed, Web of Science, Scopus, and EMBASE. Differences between cases and controls were expressed as mean difference (MD) with 95% confidence intervals (95%CI) for continuous variables, and as Odds Ratio (OR) with 95%CI for dichotomous variables. Results: Fourteen studies (332 CS, 462 controls) were included. Compared with controls, CS patients showed higher IMT (MD: 0.20 mm; 95% CI: 0.12, 0.28; p < .001), increased prevalence of carotid plaques (OR: 8.85, 95% CI: 4.09, 19.14; p < .001), and lower FMD (MD: -2.65%; 95% CI: -3.65, -1.65; p < .001). Difference in IMT and in the prevalence of carotid plaques was confirmed also in patients with CS remission (MD: 0.24 mm; 95% CI: 0.07, 0.40; p = .005 and OR: 9.88, 95% CI: 2.69, 36.3; p < 0.001, respectively). Regression models showed that age, diabetes, obesity, ACTH-dependent CS, serum and urinary cortisol levels impacted on the observed difference in IMT. Conclusions: CS is significantly associated with markers of subclinical atherosclerosis and CV risk. These findings could help establish more specific CV prevention strategies in this clinical setting. KEY MESSAGES A series of studies reported an increased cardiovascular risk in patients with Cushing's syndrome (CS). In the present meta-analysis we demonstrated that CS is associated with an increased intimamedia thickness, higher prevalence of carotid plaques, and lower flow-mediated dilation as compared with controls. These data consistently suggest the need for a strict monitoring of early signs of subclinical atherosclerosis in CS patients