Epicardial adipose tissue volume highly correlates with left ventricular diastolic dysfunction in endogenous Cushing’s syndrome

Figures & data

Figure 1. Body compositions and left ventricular diastolic function in Cushing’s syndrome and control group. Markedly increased epicardial fat volume (A) and visceral fat area (B) were observed, along with decreased skeletal muscle area (C) and skeletal muscle index (D) in CS patients. In terms of left ventricular diastolic function, CS patients exhibited a lower E/A ratio (E) and a higher prevalence of LVDD (F). CS Cushing’s syndrome, EATV epicardial adipose tissue volume, VFA visceral fat area, SMA skeletal muscle area, SMI skeletal muscle index, LVDD left ventricular diastolic dysfunction. ^***P less than 0.001.

Table 1. Characteristics of Cushing’s syndrome patients and control subjects.

Parameters	CS patients (N = 86)	Control group (N = 86)	P-value
Female, n (%)	63 (73.25%)	63 (73.25%)	1.000
Age (years)	42.80 ± 12.76	42.78 ± 12.85	0.937
BMI (kg/m^2)	24.36 ± 3.42	24.18 ± 2.97	0.713
SBP (mm Hg)	140.99 ± 19.02	117.53 ± 13.97	<0.001
DBP (mm Hg)	95.00 (85.75, 104.00)	76.00 (71.00, 82.25)	<0.001
TC (mmol/L)	5.05 (4.36, 5.88)	4.34 (3.65, 5.00)	<0.001
TG (mmol/L)	1.76 (1.26, 2.71)	1.08 (0.81, 1.47)	<0.001
HDL-C (mmol/L)	1.28 ± 0.33	1.25 ± 0.31	0.449
LDL-C (mmol/L)	3.20 (2.63, 3.61)	2.64 (2.30, 3.13)	<0.001
FBG (mmol/L)	5.95 (5.02, 7.50)	4.91 (4.63, 5.24)	<0.001
Hypertension	64 (74.42%)	6 (6.98%)	<0.001
Diabetes	42 (48.84%)	2 (2.33%)	<0.001
SUA (μmol/L)	278.00 (215.88, 370.50)	307.50 (266.75, 363.28)	0.092
Potassium (mmol/L)	3.40 (3.04, 3.86)	4.08 (3.91, 4.17)	<0.001
Sodium (mmol/L)	141.90 (140.40, 144.53)	139.95 (138.80, 141.23)	<0.001
Scr (μmol/L)	62.00 (51.00, 73.25)	62.00 (54.00, 74.25)	0.242
eGFR (ml/min/1.73m^2)	107.15 (94.95, 121.75)	107.90 (97.03, 114.60)	0.691
EATV (cm^3)	150.33 (125.67, 189.41)	90.55 (66.80, 119.84)	<0.001
VFA (cm^2)	166.81 (122.41, 216.95)	80.28 (50.06, 142.36)	<0.001
SFA (cm^2)	113.82 (90.64, 143.11)	100.86 (79.78, 139.31)	0.058
SMA (cm^2)	75.49 (65.74, 86.06)	93.18 (83.80, 111.57)	<0.001
SMI (cm^2/m^2)	28.45 (24.88, 32.30)	35.18 (32.52, 40.44)	<0.001
LVEDD (mm)	45.00 (43.00, 48.00)	45.00 (42.00, 47.00)	0.385
IVST (mm)	10.00 (10.00, 12.00)	9.00 (8.00, 10.00)	<0.001
LVPWT (mm)	10.00 (9.75, 11.00)	9.00 (8.00, 9.25)	<0.001
LAD (mm)	32.50 (30.00, 36.00)	30.00 (28.00, 33.00)	<0.001
LVEF (%)	65.00 (62.00, 68.00)	66.00 (65.00, 67.00)	0.062
E (cm/s)	71.66 ± 17.55	79.84 ± 15.67	0.002
A (cm/s)	76.90 ± 13.66	69.65 ± 15.15	0.001
E/A ratio	0.89 (0.75, 1.17)	1.24 (0.90, 1.37)	<0.001
LVDD	50 (58.14%)	23 (26.74%)	<0.001

Continuous data are presented as mean (standard deviation) and median (interquartile range) based on the normality. Categorical variables are expressed as number (%). BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; FBG, fasting blood glucose; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; SUA, serum uric acid; Scr, serum creatinine; eGFR, estimated glomerular filtration rate; EATV, epicardial adipose tissue volume; VFA, visceral fat area; SFA, subcutaneous fat area; SMA, skeletal muscle area. SMI, skeletal muscle index; LVEDD, left ventricular end-diastolic diameter; IVST, interventricular septal thickness; LVPWT, diastole left ventricular posterior wall thickness; LAD, left atrial diameter; LVEF, left ventricular ejection fraction; E, the peak velocity of early atrial inflow; A, the peak velocity of late atrial inflow; E/A ratio, the ratio of E/A; LVDD, left ventricular diastolic dysfunction.

Table 2. Comparisons of characteristics between Cushing’s syndrome subjects with or without left ventricular diastolic dysfunction.

Parameters	LVDD (N = 50)	non-LVDD (N = 36)	P-value
Female, n (%)	35 (70.00%)	28 (77.78%)	0.421
Age (years)	45.42 ± 12.52	39.17 ± 12.37	0.024
Duration (months)	10.00 (3.00, 25.50)	6.50 (1.00, 21.00)	0.222
BMI (kg/m^2)	24.43 (22.37, 26.68)	23.55 (21.64, 25.69)	0.230
SBP (mm Hg)	143.52 ± 18.20	137.47 ± 19.83	0.147
DBP (mm Hg)	96.74 ± 13.99	92.69 ± 14.85	0.201
TC (mmol/L)	5.24 ± 1.34	5.02 ± 1.12	0.437
TG (mmol/L)	1.93 (1.37, 2.77)	1.45(1.10, 2.48)	0.103
HDL-C (mmol/L)	1.22 ± 0.33	1.38 ± 0.31	0.027
LDL-C (mmol/L)	3.22 (2.72, 3.85)	3.06 (2.54, 3.47)	0.500
FBG (mmol/L)	5.95 (5.37, 7.50)	5.99 (4.60, 7.54)	0.401
Hypertension	41 (82.00%)	23 (63.89%)	0.058
Diabetes	26 (52.00%)	16 (44.44%)	0.489
SUA (μmol/L)	296.50 (213.38, 377.00)	270.50 (230.53, 364.50)	0.674
Potassium (mmol/L)	3.44 ± 0.55	3.45 ± 0.55	0.940
Sodium (mmol/L)	141.85 (140.58, 144.78)	142.00 (139.83, 144.33)	0.386
Scr (μmol/L)	66.88 ± 18.23	58.33 ± 13.62	0.020
eGFR (ml/min/1.73m^2)	106.30 (79.83, 115.18)	110.20 (104.30, 125.63)	0.019
8 am serum cortisol (μg/dL)	27.67 (21.54, 37.93)	21.94 (16.87, 33.64)	0.075
4 pm serum cortisol (μg/dL)	25.65 (19.08, 34.71)	21.19 (14.97, 26.66)	0.043
0 am serum cortisol (μg/dL)	22.33 (18.17, 26.96)	18.88 (14.91, 30.00)	0.255
EATV (cm^3)	175.28 ± 47.30	142.16 ± 48.12	0.002
VFA(cm^2)	194.06 ± 71.48	152.14 ± 73.25	0.009
SFA(cm^2)	112.46 (90.64, 147.22)	114.62 (90.38, 141.31)	0.773
SMA(cm^2)	76.22 ± 17.42	80.32 ± 20.91	0.325
SMI(cm^2/m^2)	28.80 ± 5.62	30.25 ± 7.25	0.298
LVEDD (mm)	45.00 (42.75, 49.00)	44.50 (43.25, 47.75)	0.647
IVST (mm)	10.00 (10.00, 12.00)	10.00 (10.00, 11.00)	0.167
LVPWT (mm)	10.00 (10.00, 11.00)	10.00 (9.00, 11.00)	0.292
LAD (mm)	32.50 (30.00, 36.00)	32.50 (30.00, 36.00)	0.447
LVEF (%)	65.00 (62.00, 67.25)	66.00 (62.25, 68.00)	0.424
E (cm/s)	60.50 (51.00, 70.25)	80.50 (77.25, 95.00)	<0.001
A (cm/s)	78.00 (71.75, 88.25)	70.05 (59.75, 81.00)	0.001
E/A ratio	0.77 (0.67, 0.85)	1.19 (1.09, 1.34)	<0.001

Continuous data are presented as mean (standard deviation) and median (interquartile range) based on the normality. Categorical variables are expressed as number (%). BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; FBG, fasting blood glucose; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; SUA, serum uric acid; Scr, serum creatinine; eGFR, estimated glomerular filtration rate; EATV, epicardial adipose tissue volume; VFA, visceral fat area; SFA, subcutaneous fat area; SMA, skeletal muscle area. SMI, skeletal muscle index; LVEDD, left ventricular end-diastolic diameter; IVST, interventricular septal thickness; LVPWT, diastole left ventricular posterior wall thickness; LAD, left atrial diameter; LVEF, left ventricular ejection fraction; E, the peak velocity of early atrial inflow; A, the peak velocity of late atrial inflow; E/A ratio, the ratio of E/A.

Figure 2. Correlation analysis of body compositions, biochemical indicators and E/A ratio. A negative correlation was found between the E/A ratio and EATV and VFA. There was no correlation between SMA, SMI, and the E/A ratio. HDL-C and eGFR were positively correlated with the E/A ratio. EATV epicardial adipose tissue volume, VFA visceral fat area, SMA skeletal muscle area, SMI skeletal muscle index, HDL-C high-density lipoprotein cholesterol, eGFR estimated glomerular filtration rate.

Table 3. Potential factors associated with E/A ratio in Cushing’s syndrome subjects in multiple regression analysis.

Variables	E/A ratio
	B	SE	β	95%CI	P-value
eGFR	0.004	0.001	0.358	(0.002, 0.007)	<0.001
EATV	−0.002	0.000	−0.301	(−0.003, −0.001)	0.002
HDL-C	0.183	0.074	0.227	(0.035, 0.331)	0.016

EATV, epicardial adipose tissue volume; HDL-C, high-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate; E/A ratio, the ratio of E/A.

Figure 3. Comparative analysis of epicardial adipose tissue volume in Cushing’s syndrome subjects with and without left ventricular diastolic dysfunction and ROC curve analysis. A. Significantly increased EATV in CS patients with LVDD. B. ROC analysis revealed a significant correlation between EATV and LVDD (AUC 0.698, 95%CI 0.581–0.814, p = 0.002). CS Cushing’s syndrome, EATV epicardial adipose tissue volume, LVDD left ventricular diastolic dysfunction, ROC receiver operating characteristic. ^**P less than 0.01.

Table 4. Univariate and multivariate logistic regression analysis for the association of left ventricular diastolic dysfunction with various factors in Cushing’s syndrome subjects.

Variables	Univariate			Multivariate
	B	P-value	OR(95%CI)	B	P-value	OR(95%CI)
Age	0.049	0.019	1.050 (1.008, 1.094)
HDL-C	−1.387	0.062	0.250 (0.058, 1.073)	−1.877	0.022	0.153 (0.031, 0.758)
Scr	0.031	0.058	1.031 (0.999, 1.064)
eGFR	−0.033	0.013	0.967 (0.942, 0.993)	−0.036	0.008	0.965 (0.940, 0.991)
EATV	0.014	0.015	1.014 (1.003,1.025)	0.015	0.011	1.015 (1.003, 1.026)
VFA	0.008	0.034	1.008 (1.001,1.015)

HDL-C, high-density lipoprotein cholesterol; Scr, serum creatinine; eGFR, estimated glomerular filtration rate; EATV, epicardial adipose tissue volume; VFA, visceral fat area.

Data availability statement

All data produced or analyzed during this study are incorporated in this article or displayed in supplementary material.