Non-alcoholic fatty liver disease fibrosis score is a useful tool for carotid atherosclerosis screening in patients with obstructive sleep apnea

Table 1 Characteristics of the study population, n (%)/mean ± SD

Features	Control (n = 32)	OSA (n = 112)	P value
Age (years)	54.38 ± 8.64	58.68 ± 8.64	0.014
Gender			0.015
Women	20 (62.5)	42 (37.5)
Men	12 (37.5)	70 (62.5)
Body mass index (kg/m2)	28.91 ± 5.54	30.34 ± 5.79	0.215
Arterial hypertension	9 (28.1)	59 (52.7)	0.016
Previous history of CVD	1 (3.1)	12 (10.7)	0.298
Current smoking	10 (31.2)	24 (21.4)	0.345
Diabetes mellitus type 2	2 (6.3)	16 (14.3)	0.363
Glucose (mg/dL)	97.38 ± 13.37	105.60 ± 29.92	0.071
Insulin levels (μU/L)	11.54 ± 13.26	17.19 ± 13.26	0.001
HOMA-IR score	2.93 ± 2.27	5.13 ± 8.20	0.001
Glycated Hb (%)	5.62 ± 0.53	5.70 ± 0.74	0.668
Triglycerides (mg/dL)	106.47 ± 66.57	138.41 ± 81.74	0.006
Total cholesterol	196.81 ± 39.17	192.22 ± 33.73	0.514
HDL cholesterol (mg/dL)	57.53 ± 12.96	54.30 ± 18.65	0.361
LDL cholesterol (mg/dL)	115.22 ± 30.75	110.21 ± 32.98	0.443
VLDL cholesterol (mg/dL)	21.25 ± 13.24	27.45 ± 15.11	0.005
Creatinine (mg/dL)	0.89 ± 0.16	0.89 ± 0.18	0.847
Glomerular filtration rate (mL/minute/1.73 m2)	83.98 ± 14.81	85.46 ± 16.04	0.640
ALT (IU/L)	18.78 ± 7.34	24.71 ± 14.38	0.008
AST (IU/L)	20.28 ± 5.61	22.76 ± 11.64	0.379
GGT (IU/L)	22.19 ± 13.03	34.46 ± 25.75	0.001
Iron (μg/dL)	78.47 ± 33.50	88.28 ± 28.81	0.104
Ferritin (ng/mL)	87.41 ± 72.14	143.89 ± 96.55	0.003
Transferrin (mg/dL)	244.26 ± 31.59	249.51 ± 36.54	0.468
Alkaline phosphatase (IU/L)	69.63 ± 22.69	66.54 ± 18.74	0.435
Lactate dehydrogenase (U/L)	182.72 ± 36.12	185.38 ± 36.60	0.718
Albumin (g/dL)	4.38 ± 0.27	4.44 ± 0.27	0.115
Platelets (109/L)	226.30 ± 71.27	228.20 ± 52.87	0.892
C reactive protein (mg/L)	0.42 ± 0.59	0.37 ± 0.41	0.953

OSA: Obstructive sleep apnea; CVD: Cardiovascular disease; HOMA-IR: Homeostatic model assessment-insulin resistance; Hb: Hemoglobin; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; VLDL: Very low-density lipoprotein; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyltransferase.

Table 2 Characteristics of patients with obstructive sleep apnea according to carotid atherosclerosis, n (%)/mean ± SD

Features	OSA without carotid plaque (n = 67)	OSA with carotid plaque (n = 45)	P value
Age (years)	56.30 ± 7.72	62.22 ± 8.79	> 0.001
Gender			0.237
Women	22 (32.8)	20 (44.4)
Men	45 (67.2)	25 (55.6)
Body mass index (kg/m2)	29.87 ± 5.52	31.04 ± 6.16	0.297
Arterial hypertension	25 (37.3)	34 (75.6)	> 0.001
Previous history of CVD	2 (3.0)	10 (22.2)	0.003
Current smoking	10 (14.9)	14 (31.1)	0.059
Diabetes mellitus type 2	9 (13.4)	7 (15.6)	0.788
Glucose (mg/dL)	107.43 ± 36.34	102.87 ± 16.26	0.684
Insulin levels (μU/L)	17.34 ± 14.93	16.96 ± 10.45	0.870
HOMA-IR score	5.46 ± 10.24	4.64 ± 3.45	0.959
Glycated Hb (%)	5.71 ± 0.83	5.68 ± 0.59	0.741
Triglycerides (mg/dL)	143.43 ± 88.10	130.93 ± 71.54	0.481
Total cholesterol	196.45 ± 30.34	185.93 ± 37.71	0.106
HDL cholesterol (mg/dL)	52.70 ± 16.59	56.69 ± 21.33	0.269
LDL cholesterol (mg/dL)	117.21 ± 30.02	99.78 ± 34.73	0.006
VLDL cholesterol (mg/dL)	28.30 ± 15.63	26.18 ± 14.38	0.411
Creatinine (mg/dL)	0.88 ± 0.18	0.92 ± 0.19	0.244
Glomerular filtration rate (mL/minute/1.73 m2)	88.93 ± 15.06	80.31 ± 16.22	0.005
ALT (IU/L)	25.34 ± 15.55	23.76 ± 12.57	0.846
AST (IU/L)	22.03 ± 8.54	23.84 ± 15.18	0.671
GGT (IU/L)	35.94 ± 26.64	32.24 ± 24.47	0.870
Iron (μg/dL)	88.67 ± 24.33	87.69 ± 34.72	0.200
Ferritin (ng/mL)	141.73 ± 99.48	147.14 ± 93.01	0.775
Transferrin (mg/dL)	252.55 ± 36.01	244.98 ± 37.26	0.284
Alkaline phosphatase (IU/L)	68.07 ± 19.66	64.24 ± 17.24	0.291
Lactate dehydrogenase (U/L)	179.13 ± 33.73	195.59 ± 39.17	0.023
Albumin (g/dL)	4.52 ± 0.25	4.32 ± 0.27	> 0.001
Platelets (109/L)	238.30 ± 50.51	213.00 ± 53.21	0.012
C reactive protein (mg/L)	0.38 ± 0.42	0.34 ± 0.41	0.612

OSA: Obstructive sleep apnea; CVD: Cardiovascular disease; HOMA-IR: Homeostatic model assessment-insulin resistance; Hb: Hemoglobin; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; VLDL: Very low-density lipoprotein; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyltransferase.

Table 3 Respiratory features of patients with obstructive sleep apnea according to carotid atherosclerosis, n (%)/mean ± SD

Respiratory features	OSA without carotid plaque (n = 67)	OSA with carotid plaque (n = 45)	P value
AHI (events/hour)	32.48 ± 41.05	29.28 ± 20.97	0.812
5-14	24 (35.8)	13 (28.9)	0.540
15-29	16 (23.9)	15 (33.3)	0.289
≥ 30	27 (40.3)	17 (37.8)	0.845
ODI (events/hour)	25.95 ± 18.81	30.00 ± 21.17	0.294
≥ 10	53 (79.1)	40 (88.9)	0.422
Tc90%	20.42 ± 26.24	23.13 ± 25.56	0.321
≥ 10%	29 (43.3)	23 (51.1)	0.562

OSA: Obstructive sleep apnea; AHI: Apnea-hypopnea index; ODI: Oxygen desaturation index; Tc90%: Percentage of sleep time with oxygen saturation less than 90%.

Table 4 Metabolic and hepatic characterization of patients with obstructive sleep apnea according to carotid atherosclerosis, n (%)

Features	OSA without carotid plaque (n = 67)	OSA with carotid plaque (n = 45)	P value
Body mass index ≥ 30	28 (41.8)	24 (53.3)	0.251
HOMA-IR score ≥ 3	41 (61.2)	28 (62.2)	1.000
Dyslipidemia	29 (43.3)	24 (53.3)	0.338
Metabolic syndrome	17 (25.4)	8 (17.8)	0.367
Simple steatosis by OWLiver™ test	20 (29.9)	15 (33.3)	0.836
Steatohepatitis by OWLiver™ test	37 (55.2)	19 (42.2)	0.247
FLI (a.u.)	66.58 ± 27.09	68.88 ± 29.99	0.486
FLI ≥ 60	41 (61.2)	32 (71.1)	0.317
FSI (a.u.)	0.34 ± 0.25	0.43 ± 0.26	0.035
FSI ≥ 0.23	37 (55.2)	36 (80.0)	0.009
NFS (a.u.)	-1.54 ± 0.95	-0.75 ± 1.10	> 0.001
NFS < -1.455	39 (58.2)	11 (24.4)	> 0.001
FIB-4 (a.u.)	1.12 ± 0.38	1.57 ± 1.05	> 0.001
FIB-4 < 1.3	50 (74.6)	21 (46.7)	0.002
HFS (a.u.)	0.06 ± 0.08	0.12 ± 0.18	0.005
HFS < 0.12	55 (82.1)	34 (75.6)	0.477

HOMA-IR: Homeostatic model assessment-insulin resistance; a.u.: Arbitrary units; FLI: Fatty liver index; FSI: Framingham steatosis index; FIB-4: Fibrosis-4; NFS: Non-alcoholic fatty liver disease fibrosis score; HFS: Hepamet fibrosis score.

Table 5 Univariate and multivariate analysis of non-alcoholic fatty liver disease fibrosis score and the independent variables associated with carotid atherosclerosis in patients with obstructive sleep apnea (n = 112)

Independent variables	Univariate analysis			Multivariate analysis
	OR	95%CI	P value	OR	95%CI	P value
NFS (a.u.)	2.16	1.41-3.33	< 0.001	1.84	1.16-2.93	0.010
Sex (female/male)	0.61	0.28-1.33	0.215	-	-	-
Arterial hypertension (yes/no)	5.19	2.24-12.04	< 0.001	3.67	1.46-9.20	0.006
Previous history of CVD (yes/no)	9.29	1.93-44.76	0.005	-	-	-
Current smoking (yes/no)	2.57	1.02-6.47	0.044	3.10	0.99-9.66	0.052
LDL-c (mg/dL)	0.98	0.97-0.99	0.007	-	-	-
GFR (mL/minute/1.73 m2)	0.96	0.94-0.99	0.007	-	-	-
LDH (U/L)	1.01	1.00-1.02	0.033	-	-	-
AHI (events/hour)	1.00	0.98-1.01	0.633	-	-	-
ODI (events/hour)	1.01	0.99-1.03	0.292	-	-	-
Tc90%	1.00	0.99-1.02	0.586	-	-	-

Multivariate model was built following forward introduction of the variables selected by likelihood ratio test. Hosmer-Lemshow test was performed to evaluate goodness of fit of the model (P = 0.268). OR: Odds ratio; CI: Confidence interval; NFS: NAFLD fibrosis score; a.u.: Arbitrary units; CVD: Cardiovascular disease; LDL-c: Low-density lipoprotein cholesterol; GFR: Glomerular filtration rate; LDH: Lactate dehydrogenase; AHI: Apnea-hypopnea index; ODI: Oxygen desaturation index; Tc90%: Percentage of sleep time with oxygen saturation less than 90%.

Table 6 Univariate and multivariate analysis of fibrosis-4 index and the independent variables associated with carotid atherosclerosis in patients with obstructive sleep apnea (n = 112)

Independent variables	Univariate analysis			Multivariate analysis
	OR	95%CI	P value	OR	95%CI	P value
FIB-4 (a.u.)	2.16	1.41-3.33	0.004	5.53	1.72-17.70	0.004
Sex (female/male)	0.61	0.28-1.33	0.215	-	-	-
Arterial hypertension (yes/no)	5.19	2.24-12.04	< 0.001	3.84	1.42-10.36	0.008
Previous history of CVD (yes/no)	9.29	1.93-44.76	0.005	-	-	-
Current smoking (yes/no)	2.57	1.02-6.47	0.044	3.89	1.21-12.50	0.022
Diabetes (yes/no)	1.19	0.41-3.46	0.753	-	-	-
LDL-c (mg/dL)	0.98	0.97-0.99	0.007	-	-	-
GFR (mL/minute/1.73 m2)	0.96	0.94-0.99	0.007	-	-	-
LDH (U/L)	1.01	1.00-1.02	0.033	-	-	-
Albumin (g/dL)	0.72	0.60-0.87	< 0.001	0.76	0.61-0.95	0.016
AHI (events/hour)	1.00	0.98-1.01	0.633	-	-	-
ODI (events/hour)	1.01	0.99-1.03	0.292	-	-	-
Tc90%	1.00	0.99-1.02	0.586	-	-	-

Multivariate model was built following forward introduction of the variables selected by likelihood ratio test. Hosmer-Lemshow test was performed to evaluate goodness of fit of the model (P = 0.883). OR: Odds ratio; CI: Confidence interval; NFS: NAFLD fibrosis score; a.u.: Arbitrary units; CVD: Cardiovascular disease; LDL-c: Low-density lipoprotein cholesterol; GFR: Glomerular filtration rate; LDH: Lactate dehydrogenase; AHI: Apnea-hypopnea index; ODI: Oxygen desaturation index; Tc90%: Percentage of sleep time with oxygen saturation less than 90%.

Table 7 Univariate and multivariate analysis of the framingham steatosis index and the independent variables associated with carotid atherosclerosis in patients with obstructive sleep apnea (n = 112)

Independent variables	Univariate analysis			Multivariate analysis
	OR	95%CI	P value	OR	95%CI	P value
FSI (a.u.)	4.31	0.95-19.51	0.058	-	-	-
Previous history of CVD (yes/no)	9.29	1.93-44.76	0.005	14.09	2.52-78.92	0.003
Current smoking (yes/no)	2.57	1.02-6.47	0.044	-	-	-
LDL-c (mg/dL)	0.98	0.97-0.99	0.007	-	-	-
GFR (mL/minute/1.73 m2)	0.96	0.94-0.99	0.007	-	-	-
LDH (U/L)	1.01	1.00-1.02	0.033	1.02	1.00-1.03	0.014
Albumin (g/dL)	0.72	0.60-0.87	< 0.001	0.71	0.58-0.88	0.002
Platelets (109/L)	0.99	0.98-1.00	0.016	-	-	-
AHI (events/hour)	1.00	0.98-1.01	0.633	-	-	-
ODI (events/hour)	1.01	0.99-1.03	0.292	-	-	-
Tc90%	1.00	0.99-1.02	0.586	-	-	-

Multivariate model was built following forward introduction of the variables selected by likelihood ratio test. Hosmer-Lemshow test was performed to evaluate goodness of fit of the model (P = 0.108). OR: Odds ratio; CI: Confidence interval; a.u.: Arbitrary units; FSI: Framingham steatosis index; CVD: Cardiovascular disease; LDL-c: Low-density lipoprotein cholesterol; GFR: Glomerular filtration rate; LDH: Lactate dehydrogenase; AHI: Apnea-hypopnea index; ODI: Oxygen desaturation index; Tc90%: Percentage of sleep time with oxygen saturation less than 90%.