Early-stage non-alcoholic fatty liver disease in relation to atherosclerosis and inflammation

Tan, Si-hua; Zhou, Xiao-li

doi:10.1016/j.clinsp.2023.100301

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Sumário

Original articles • Clinics 78 • 2023 • https://doi.org/10.1016/j.clinsp.2023.100301 copy

Early-stage non-alcoholic fatty liver disease in relation to atherosclerosis and inflammation

Authorship SCIMAGO INSTITUTIONS RANKINGS

Highlight

Non-alcoholic fatty liver disease was associated with carotid intimal thickening and non-calcified plaque, highlighting an elevated cardiovascular risk.
NAFLD fibrosis is an independent risk factor for CHD.
Inflammation potentially serves as a complete mediator in the connection between NAFLD fibrosis and CHD.

Abstract

Background and aims

Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease closely linked to cardiovascular disease (CVD). This study aims to investigate the connection between early-stage NAFLD and atherosclerosis, as well as the correlation between liver fibrosis and coronary heart disease while exploring underlying inflammatory mechanisms.

Methods

In this retrospective study, the authors analyzed data from 607 patients who underwent both coronary computed tomography angiography (CCTA) and abdominal ultrasonography (US). Logistic regression was utilized to examine the association between NAFLD and atherosclerosis, while mediation analysis was conducted to explore whether inflammatory markers mediate the link between liver fibrosis and coronary artery disease.

Results

Among the 607 patients included, 237 (39.0 %) were diagnosed with NAFLD through ultrasonography. After adjusting for traditional cardiovascular risk factors, ALT, and AST, NAFLD demonstrated a significant correlation with carotid intimal thickening (1.58, 95 % CI 1.04‒2.40; p= 0.034) and non-calcified plaque (1.56, 95 % CI 1.03‒2.37; p= 0.038). Additionally, fibrosis predictive markers, including FIB-4 > 1.3 (1.06, 95 % CI 2.30‒5.00; p= 0.035) and APRI (6.26, 95 % CI 1.03‒37.05; p= 0.046), independently correlated with coronary heart disease after adjusting for cardiovascular risk factors. Conversely, among systemic inflammatory markers, only the neutrophil-to-lymphocyte ratio (NLR) and systemic inflammatory response index (SIRI) are independently associated with coronary heart disease. ROC curve analysis indicated that combining predictive fibrosis markers or inflammatory markers with traditional cardiovascular risk factors enhanced the predictive accuracy for coronary heart disease. Mediation analysis revealed that NLR fully mediated the effect of liver fibrosis on coronary heart disease.

Conclusion

NAFLD is associated with carotid intimal thickening and non-calcified plaque, suggesting an increased cardiovascular risk. Furthermore, liver fibrosis independently increases the risk of coronary heart disease in the early-stage NAFLD population, and inflammation may play a fully mediating role in the effect of liver fibrosis on coronary heart disease. Early intervention is crucial for NAFLD patients to mitigate future major adverse cardiovascular events.

Keywords
Atherosclerosis; Coronary heart disease; Non-alcoholic fatty liver disease; Liver fibrosis; Inflammation

Characteristics	Overall (n= 607)	Non-NAFLD (n= 370)	NAFLD (n= 237)	p-value
Age (year), mean ± SD	62.4 ± 10.3	62.8 ± 10.8	61.8 ± 9.4	0.264
Male, n (%)	210 (34.6)	114 (30.8)	96 (40.5)	0.014
Smoking, n (%)	129 (21.3)	66 (17.8)	63 (26.6)	0.010
Family history of CVD, n (%)	174 (28.7)	86 (23.2)	88 (37.1)	<0.001
Diabetes mellitus, n (%)	180 (29.7)	70 (18.9)	110 (46.4)	<0.001
Hypertension, n (%)	337 (55.5)	190 (51.4)	147 (62.0)	<0.010
Systolic blood pressure (mmHg), mean ± SD	133.0 ± 18.6	131.9 ± 18.7	134.8 ± 18.2	0.065
Diastolic blood pressure (mmHg), mean ± SD	79.3 ± 11.9	78.1 ± 12.1	81.1 ± 11.5	0.002
BMI (kg/m²), mean ± SD	24.1 ± 2.8	23.1 ± 2.8	25.5 ± 2.2	<0.001
Urea (mmol/L), mean ± SD	5.7 ± 3.0	5.7 ± 3.6	5.7 ± 1.6	0.989
Creatinine (μmoL/L), mean ± SD	68.1 ± 23.7	66.9 ± 18.5	69.9 ± 30.0	0.126
Uric acid (μmoL/L), mean ± SD	232.7 ± 81.0	300.9 ± 73.2	333.8 ± 88.3	<0.001
Albumin (g/L), mean ± SD	43.5 ± 3.9	43.4 ± 4.1	43.6 ± 3.5	0.630
TBIL (μmoL/L), median (IQR)	9.5 (5.5)	9.7 (5.6)	9.3 (4.9)	0.822
DBIL (μmoL/L), median (IQR)	4.0 ± 1.8	4.0 ± 1.9	4.0 ± 1.7	0.696
ALT (U/L), median (IQR)	18 (13)	16 (11)	22 (15)	<0.001
AST (U/L), median (IQR)	19 (7)	18 (8)	20 (9)	0.001
GGT (U/L), median (IQR)	21 (17)	18 (13)	26 (17)	<0.001
Total cholesterol (mmoL/L), median (IQR)	1.4 (1.0)	1.2 (0.7)	1.7 (1.2)	<0.001
Triglyceride (mmoL/L), mean ± SD	4.7 ± 1.0	4.7 ± 0.9	4.6 ± 1.0	0.500
HDL-C (mmoL/L), mean ± SD	1.3 ± 0.4	1.4 ± 0.4	1.1 ± 0.3	<0.001
LDL-C (mmoL/L), mean ± SD	2.9 ± 0.9	2.9 ± 0.8	2.9 ± 0.9	0.922
Hs-CRP (mg/L), median (IQR)	0.9 (1.4)	0.7 (1.1)	1.2 (1.7)	<0.001
HbA1C (%), median (IQR)	5.8 (0.7)	5.7 (0.5)	6.1 (1.4)	<0.001
FBG (mmoL/L), median (IQR)	5.5 (1.2)	5.3 (0.9)	5.8 (2.2)	<0.001
Fibrosis markers
FIB-4, median (IQR)	1.3 (0.8)	1.4 (0.7)	1.3 (0.7)	0.078
APRI, median (IQR)	0.27 (0.15)	0.27 (0.16)	0.27 (0.14)	0.002

Variables	Overall (n= 607)	Non-NAFLD (n= 370)	NAFLD (n= 237)	p-value
Carotid intima thickening, n (%)	334 (55.0)	187 (50.5)	147 (62.0)	0.006
Coronary atherosclerotic plaque, n (%)	278 (45.8)	153 (41.4)	125 (52.7)	0.006
Plaque type, n (%)
Calcified plaque	188 (31.0)	100 (27.0)	88 (37.1)	0.009
Non-calcified plaque	178 (29.3)	92 (24.9)	86 (36.3)	0.003
Mixed plaque	47 (7.7)	25 (6.8)	22 (9.3)	0.256
CHD, n (%)	99 (16.3)	47 (12.7)	52 (21.9)	0.003
CACS, median (IQR)	0.0 (17.5)	0.0 (11.1)	0.0 (29.2)	0.033
CACS classification, n (%)				0.038
0	401 (66.1)	258 (69.7)	143 (60.3)
1‒10	43 (7.1)	20 (5.4)	23 (9.7)
11‒100	82 (13.5)	47 (12.7)	35 (14.8)
101‒400	55 (9.1)	27 (7.3)	28 (11.8)
>400	26 (4.3)	18 (4.9)	8 (3.4)

Variables	Univariate		Multivariate
Variables	Odds ratio (95 % CI)	p-value	Odds ratio (95 % CI)	p-value
hs-CRP	0.99 (0.89‒1.09)	0.814	0.96 (0.85‒1.09)	0.538
NLR	1.81 (1.31‒2.50)	<0.001	1.56 (1.08‒2.26)	0.018
PLR	1.01 (0.99‒1.02)	0.320	1.01 (1.00‒1.03)	0.197
LMR	0.90 (0.77‒1.04)	0.015	0.92 (0.78‒1.10)	0.361
MHR	3.23 (0.78‒13.50)	0.107	3.94 (0.45‒34.42)	0.215
SII	1.00 (1.00‒1.01)	0.119	1.00 (0.99‒1.00)	0.477
SIRI	2.29 (1.45‒3.60)	<0.001	1.95 (1.16‒3.27)	0.012

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[1] ⁎ Corresponding author. E-mail address: 229050878@qq.com, zhouxiaolicqmu@163.com (X.-l. Zhou).