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

Figures & data

Table 1. Demographic and clinical data of patients with CS and controls in included studies.

Author	Population (n)	ACTHd (%)	M/F (n)	Age (years)	HT (%)	Smoking (%)	DM (%)	Ob (%)	HL (%)	BMI (kg/m^2)	TC (mmol/l)	LDLc (mmol/l)	HDLc (mmol/l)	TGs (mmol/l)
Active CS
Akaza (11)
CS	21	38.1	4/17	55	90	–	57	–	38	23.7	–	2.84	1.58	1.28
Controls	12	–	3/9	56	83	–	67	–	41	25.1	–	3.05	1.55	1.66
Albiger (9)
CS	28	85.7	5/23	40.7	78.6	–	10.7	25	71	27	5.70	3.40	1.50	1.40
Controls	28	–	5/23	41.1	78.6	–	7.1	18	61	26.8	5.40	3.20	1.51	1.50
Bassareo (22)
CS	23	86.9	0/23	14.3	–	–	–	39	–	28.3	–	–	–	–
Controls	23	–	0/23	14.9	–	–	–	–	–	20.8	–	–	–	–
Baykan (18)
CS	22	54.5	10/12	42	45.5	–	27.3	–	–	28	5.32	3.80	1.27	1.83
Controls	23	–	10/13	43	39.1	–	21.7	–	–	27	5.30	3.82	1.24	1.86
Evran^b (23)
CS	5	0	–	49.6	0	–	0	–	–	31.8	5.16	3.36	1.2	1.62
Controls	33	–	–	48.9	0	–	0	–	–	27.5	4.88	3.05	1.25	1.27
Faggiano (20)
CS	25	100	8/17	34.2	72	0	20	32	52	29.2	6.20	4.35	1.00	1.95
Controls	32	–	–	–	9.4	0	0	0	0	22.8	4.50	2.67	1.44	1.51
Jezkovà^a (12)
CS	14	–	–	–	–	–	–	–	–	––	–	–	–	–
Controls	16	–	–	–	–	–	–	–	–	–	–	–	–	–
Ozsurekci (25)
CS	27	78	3/24	42.1	58.3	0	48	–	26	32.3	5.94	3.53	1.33	2.08
Controls	27	–	3/24	42	51.2	0	48	–	30	31.8	4.79	2.94	1.11	1.58
Petramala (8)
CS	30	40	4/26	54.9	–	16.7	–	–	–	28.6	5.66	2.89	–	1.42
Controls	30	–	–	46.3	–	23.3	–	–	–	25.6	4.65	3.02	–	1.26
Reimondo^b (26)
CS	12	0	4/8	60	66.7	–	41.7§	–	–	27.4	–	–	–	–
Controls	32	–	13/19	–	–	–	–	–	–	–	–	–	–	–
Shivaprasad (10)
CS	22	78.2	0/22	31.7	68.2	–	–	–	–	27.1	5.44	3.12	1.13	2.59
Controls	33	–	0/33	35.2	18.2	–	–	–	–	24.2	4.80	2.89	1.28	1.36
Tauchamanovà^b (21)
CS	28	0	–	56.4	60.7	7.1	35.7	32.1	71.4	27	5.61	3.65	1.27	1.90
Controls	100	–	–	55	–	6	–	22	–	26.7	4.65	3.13	1.45	1.24
CS after remission
Bassareo (22)
CS	23	86.9	0/23	–	–	–	–	–	–	29.1	–	–	–	–
Controls	23	–	0/23	14.9	–	–	–	–	–	20.8	–	–	–	–
Colao (19)
CS	15	100	3/12	25	40	0	33.3	40	26.7	28.5	5.51	3.59	1.24	1.48
Controls	30	–	–	–	10	0	0	0	0	23.5	4.53	2.56	1.60	1.21
Faggiano (20)
CS	25	100	8/17	34.2	40	0	12	20	40	26.8	5.50	3.75	1.12	1.80
Controls	32	–	–	–	9.4	0	0	0	0	22.8	4.50	2.67	1.44	1.51
Jezkovà (12)
CS	27	–	–	–	–	–	–	–	–	–	–	–	–	–
Controls	17		–	–	–	–	–	–	–	–	–	–	–	–
Wagenmakers (24)
CS	58	69.0	12/46	46.8	31	24.1	6.9	–	20.7	26.5	–	–	–	–
Controls	58	–	12/46	45.7	0	8.6	0	–	0	26.3	–	–	–	–

ACTHd: ACTH-dependent Cushing disease; BMI: body mass index; CS: Cushing syndrome; DM: diabetes mellitus; HDLc: HDL-cholesterol; HL: hyperlipidemia; HT: hypertension; LDLc: LDL-cholesterol; M/F: male/female; NA: not assessed; Ob: obesity; TC: total cholesterol; TGs: triglycerides. Age, BMI, TC, LDLc, HDLc, and TGs are expressed as mean values, unless otherwise indicated.

^aOnly abstract available.

^bStudy on subclinical CS.

Figure 1. CCA-IMT (Panel A) and prevalence of carotid plaques (Panel B) in patients with active CS and controls.

Figure 2. FMD in patients with active CS and controls.

Figure 3. CCA-IMT (Panel A) and prevalence of carotid plaques (Panel B) in patients with CS after remission and controls.

Table 2. Sensitivity analyses on “high quality” studies (i.e., Newcastle–Ottowa scale ≥5).

Active CS	No of studies	No of patients	Effect size MD or OR [95%CI]
Carotid IMT	10	221 patients 350 controls	MD: 0.20 [0.12, 0.28]; p < .001 I^2 = 96%; p < .0001
Carotid plaques	4	111 patients 190 controls	OR: 8.66 [3.21, 23.38]; p < .001 I^2 = 19%; p = .30
FMD	3	65 patients 68 controls	MD: −2.65 [−3.65, −1.65]; p < .001 I^2 = 0%; p = .42
After CS remission
Carotid IMT	4	121 patients 143 controls	MD: 0.24 [0.07, 0.40]; p = .001 I^2 = 98%; p < .001
Carotid plaques	2	40 patients 62 controls	OR: 27.57 [3.41, 222.62]; p = .002 I^2 = 0%; p = .89

95% CI: 95% confidence intervals; CD: Cushing disease; FMD: flow-mediated dilation; IMT: intima-media thickness; MD: mean difference; N: number; OR: odds ratio.

Figure 4. Meta-regression analyses. Effects of age, diabetes, obesity, ACTH-dependent hypercortisolism, serum cortisol levels and free urinary cortisol levels on CCA-IMT in patients with active CS.

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