Sex-Specific Contribution of Cardiometabolic Index in Predicting Metabolic Dysfunction-Associated Fatty Liver Disease: Insights from a General Population

Figures & data

Figure 1 Flowchart of participants excluded and included in this study.

Table 1 Baseline Characteristics of the Study Population According to Sex (n=6107)

Variables	Overall (n=6107)	Males (n=3851)		t, Z/χ^2	P-value	Females (n=2256)		t, Z/χ^2	P-value
		Non-MAFLD (n=2175)	MAFLD (n=1676)			Non-MAFLD (n=1890)	MAFLD (n=366)
Age (years)	46.00 (37.00~55.00)	46.00 (36.00~55.00)	48.00 (40.00~56.00)	−5.08	<0.001	43.00 (34.75~52.00)	54.00 (45.00~60.00)	−12.78	<0.001
Smoking, n (%)	1594 (26.1)	796 (36.6)	792 (47.3)	44.37	<0.001	5(0.3)	1(0.3)	0.001	0.976
Drinking, n (%)	1023 (16.8)	541 (24.9)	463 (27.6)	3.72	0.054	15 (0.8)	4(1.1)	0.329	0.533
WC (cm)	82.65±9.55	73.79±6.66	83.52±7.30	31.85	<0.001	83.76±6.58	91.03±7.35	23.65	<0.001
BMI (kg/m^2)	24.49±3.27	22.27±2.50	25.98±3.25	32.67	<0.001	24.17±2.44	27.10±2.97	20.70	<0.001
WHtR	0.49±0.05	0.49±0.04	0.53±0.05	30.71	<0.001	0.46±0.04	0.53±0.05	24.26	<0.001
CMI	0.50 (0.29~0.88)	0.48 (0.32~0.75)	0.99 (0.68~1.49)	−31.56	<0.001	0.26 (0.18~0.40)	0.65 (0.44~0.95)	−21.41	<0.001
SBP (mmHg)	122.00 (111.00~132.00)	123.00 (114.00~132.00)	129.00 (120.00~137.00)	−12.77	<0.001	112.00 (103.00~123.00)	123.50 (113.85~134.00)	−12.87	<0.001
DBP (mmHg)	73.00 (66.00~80.00)	73.00 (67.00~80.00)	78.00 (71.00~85.00)	−14.90	<0.001	69.00 (62.00~75.00)	73.00 (68.00~82.00)	−9.83	<0.001
Hypertension, n (%)	777 (12.7)	238 (10.9)	351 (20.9)	73.07	<0.001	122 (6.5)	66 (18.0)	53.81	<0.001
Dyslipidemia, n (%)	2517 (41.2)	803 (36.9)	993 (59.2)	189.63	<0.001	544 (28.8)	177 (48.4)	54.05	<0.001
Diabetes, n (%)	388 (6.4)	91 (4.2)	226 (13.5)	108.40	<0.001	24 (1.3)	47 (12.8)	134.70	<0.001
FBG (mmol/L)	5.20 (4.91~5.60)	5.18 (4.92~5.54)	5.47 (5.12~6.09)	−16.03	<0.001	5.00 (4.76~5.27)	5.47 (5.14~6.02)	−15.59	<0.001
TG (mmol/L)	1.28 (0.89~1.92)	1.23 (0.92~1.72)	2.00 (1.46~2.76)	−27.52	<0.001	0.89 (0.69~1.20)	1.54 (1.16~2.10)	−19.28	<0.001
TC (mmol/L)	4.83 (4.27~5.40)	4.78 (4.24~5.32)	4.93 (4.37~5.52)	−5.52	<0.001	4.78 (4.22~5.36)	4.95 (4.44~5.59)	−4.03	<0.001
HDL-C (mmol/L)	1.26 (1.07~1.52)	1.25 (1.09~1.45)	1.06 (0.92~1.21)	−23.49	<0.001	1.54 (1.32~1.78)	1.25 (1.09~1.45)	−14.65	<0.001
LDL-C (mmol/L)	3.11 (2.60~3.61)	3.13 (2.64~3.61)	3.21 (2.67~3.74)	−3.37	<0.001	2.96 (2.48~3.49)	3.23 (2.68~3.73)	−5.21	<0.001
ALT (IU/L)	18.00 (13.00~27.00)	18.00 (14.00~24.00)	28.00 (20.00~41.00)	−26.20	<0.001	13.00 (10.00~17.00)	22.00 (16.00~31.25)	−18.13	<0.001
AST (IU/L)	17.00 (14.00~21.00)	17.00 (14.10~20.00)	20.00 (16.00~25.00)	−15.97	<0.001	15.00 (13.00~18.00)	18.00 (15.00~23.00)	−9.48	<0.001
WBC (×10^9/L)	6.05 (5.14~7.04)	6.09 (5.18~7.00)	6.63 (5.75~7.64)	−12.24	<0.001	5.48 (4.69~6.45)	6.10 (5.27~7.08)	−7.65	<0.001
NE (×10^9/L)	3.27 (2.66~4.00)	3.24 (2.66~3.93)	3.61 (2.97~4.33)	−10.96	<0.001	3.01 (2.43~3.69)	3.36 (2.71~4.08)	−5.90	<0.001
LY (×10^9/L)	2.15 (1.80~2.56)	2.17 (1.84~2.56)	2.33 (1.95~2.77)	−8.14	<0.001	1.98 (1.64~2.34)	2.20 (1.87~2.52)	−6.87	<0.001

Notes: Data are presented as mean with standard deviation, median with the interquartile range [M (P25-P75)], or numbers (percentage) [n (%)] as appropriate. Comparison of the differences between the two groups were examined by Student’s t-test, Mann–Whitney U-test or chi-square test, respectively.

Abbreviations: CMI, cardiometabolic index; MAFLD, metabolic dysfunction-associated fatty liver disease; WC, waist circumference; BMI, body mass index; WHtR, waist-to-height ratio; SBP, systolic blood pressure; DBP, diastolic blood pressure; FBG, fasting blood glucose; TC, total cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; ALT, alanine aminotransferase; AST, aspartate aminotransferase; WBC, white blood cell; NE, neutrophil; LY, lymphocyte.

Table 2 Baseline Characteristics of the Study Population by CMI Quartiles According to Sex (n=6107)

Characteristics	Male (n=3851)				P-value	P for Trend	Female (n=2256)				P-value	P for Trend
	Q1 (n=963) (0.08~0.41)	Q2 (n=963) (0.42~0.67)	Q3 (n=963) (0.68~1.09)	Q4 (n=963) (1.10~17.23)			Q1 (n=564) (0.06~0.19)	Q2 (n=564) (0.20~0.30)	Q3 (n=564) (0.31~0.49)	Q4 (n=564) (0.50~11.33)
Age (years)	39.00 (32.00~46.00)	42.00 (35.00~52.00)	47.00 (39.00~57.00)	51.50 (42.00~58.00)	<0.001	<0.001	44.00 (35.00~56.00)	47.00 (38.00~56.00)	47.00 (39.00~56.25)	47.00 (40.00~55.00)	<0.001	<0.001
Smoking, n (%)	280 (29.1)	363 (37.7)	428 (44.5)	517 (53.7)	<0.001	<0.001	1(0.2)	0(0)	3(0.5)	2(0.4)	<0.001	0.273
Drinking, n (%)	198 (20.6)	248 (25.8)	244 (25.4)	314 (32.6)	<0.001	<0.001	4(0.7)	4(0.7)	6(1.1)	5(0.9)	<0.001	0.607
WC (cm)	81.65±6.56	86.15±6.59	88.53±6.91	91.36±7.69	<0.001	<0.001	70.24±5.90	73.29±5.82	77.02±6.56	80.93±7.68	<0.001	<0.001
BMI (kg/m^2)	23.57±2.49	25.07±2.55	25.92±2.77	27.21±3.15	<0.001	<0.001	21.07±2.12	22.17±2.23	23.38±2.74	24.87±3.23	<0.001	<0.001
WHtR	0.47±0.04	0.50±0.04	0.52±0.04	0.53±0.05	<0.001	<0.001	0.44±0.04	0.46±0.04	0.48±0.04	0.51±0.05	<0.001	<0.001
Hypertension, n (%)	91 (9.4)	136 (14.1)	152 (15.8)	210 (21.8)	<0.001	<0.001	10 (1.8)	34 (6.0)	61 (10.8)	83 (14.7)	<0.001	<0.001
Diabetes, n (%)	40 (4.2)	60 (6.2)	88 (9.1)	129 (13.4)	<0.001	<0.001	3(0.5)	6(1.1)	18 (3.2)	44 (7.8)	<0.001	<0.001
FBG (mmol/L)	5.15 (4.87~5.49)	5.26 (4.97~5.63)	5.36 (5.04~5.85)	5.46 (5.10~6.07)	<0.001	<0.001	4.85 (4.65~5.11)	5.00 (4.76~5.25)	5.11 (4.86~5.42)	5.30 (4.98~5.76)	<0.001	<0.001
TG (mmol/L)	0.87 (0.73~1.01)	1.28 (1.13~1.47)	1.81 (1.59~2.04)	2.98 (2.42~3.92)	<0.001	<0.001	0.61 (0.52~0.69)	0.83 (0.75~0.93)	1.11 (0.98~1.26)	1.73 (1.47~2.22)	<0.001	0.013
TC (mmol/L)	4.61 (4.10~5.16)	4.85 (4.29~5.36)	4.88 (4.32~5.44)	5.04 (4.48~5.68)	<0.001	0.369	4.70 (4.17~5.24)	4.70 (4.16~5.21)	4.84 (4.26~5.41)	5.00 (4.45~5.64)	<0.001	0.100
HDL-C (mmol/L)	1.45 (1.29~1.64)	1.22 (1.11~1.34)	1.09 (0.99~1.20)	0.95 (0.84~1.06)	<0.001	0.159	1.85 (1.66~2.04)	1.57 (1.43~1.75)	1.41 (1.27~1.55)	1.17 (1.04~1.32)	<0.001	0.017
LDL-C (mmol/L)	2.96 (2.49~3.45)	3.28 (2.80~3.74)	3.31 (2.86~3.82)	3.10 (2.50~3.64)	<0.001	0.005	2.66 (2.29~3.18)	2.93 (2.48~3.41)	3.14 (2.66~3.65)	3.26 (2.70~3.74)	<0.001	0.018
Dyslipidemia, n (%)	222 (23.1)	318 (33.0)	490 (50.9)	766 (79.5)	<0.001	<0.001	114 (20.2)	134 (23.8)	184 (32.6)	289 (51.2)	<0.001	<0.001
ALT (IU/L)	17.00 (13.00~23.00)	20.00 (15.00~28.00)	24.00 (17.00~34.00)	28.00 (20.00~41.00)	<0.001	<0.001	11.00 (9.00~15.00)	13.00 (10.00~17.00)	14.00 (11.00~19.00)	18.00 (13.00~27.00)	<0.001	<0.001
AST (IU/L)	17.00 (15.00~20.00)	18.00 (15.00~21.00)	18.00 (15.00~22.00)	20.00 (16.00~26.00)	<0.001	<0.001	15.00 (13.00~18.00)	15.00 (13.00~18.00)	16.00 (13.00~19.00)	17.00 (14.00~21.00)	<0.001	<0.001
WBC (×10^9/L)	5.78 (5.01~6.61)	6.24 (5.42~7.15)	6.51 (5.56~7.45)	6.80 (5.83~7.96)	<0.001	<0.001	5.24 (4.51~6.17)	5.49 (4.75~6.52)	5.66 (4.82~6.56)	6.00 (5.08~6.94)	<0.001	<0.001
NE (×10^9/L)	3.09 (2.52~3.70)	3.32 (2.78~4.05)	3.51 (2.89~4.19)	3.70 (3.01~4.46)	<0.001	<0.001	2.86 (2.31~3.51)	3.05 (2.45~3.70)	3.13 (2.59~3.82)	3.24 (2.59~4.01)	<0.001	<0.001
LY (×10^9/L)	2.11 (1.79~2.47)	2.21 (1.87~2.61)	2.28 (1.92~2.69)	2.37 (1.99~2.87)	<0.001	<0.001	1.91 (1.59~2.26)	1.97 (1.62~2.34)	2.02 (1.70~2.38)	2.15 (1.84~2.53)	<0.001	<0.001

Notes: Continuous data are presented as mean with standard deviation or median with the interquartile range [M (P25-P75)], and categorical data as frequency (percentage) [n (%)]. Comparison of the differences among groups were examined by ANOVA, Kruskal–Wallis H-test or chi-square test according to the type and distribution pattern of variables.

Abbreviations: CMI, cardiometabolic index; WC, waist circumference; BMI, body mass index; WHtR, waist-to-height ratio; FBG, fasting blood glucose; TC, total cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; ALT, alanine aminotransferase; AST, aspartate aminotransferase; WBC, white blood cell; NE, neutrophil; LY, lymphocyte.

Figure 2 Prevalence of MAFLD according to CMI quartile by sex.

Abbreviations: MAFLD, metabolic associated fatty liver disease; CMI, cardiometabolic index.

Figure 3 The heatmap of the correlation between baseline variables and CMI using the Pearson’s correlation analysis among by sex. *P<0.05;**P<0.01;***P<0.001.

Figure 4 Restricted cubic spline of the association between CMI and MAFLD risk by sex. The association was adjusted for age, smoking, drinking, WC, BMI, WHtR, diabetes, hypertension, dyslipidemia, AST, ALT, WBC, NE and LY. The medians CMI of males (0.9) and females (0.4) were chosen as a reference. The plot showed an increased risk of MAFLD with the elevated CMI, which were above the medians of CMI.

Abbreviations: OR, odds ratio; CI, confidence intervals.

Table 3 Adjusted Associations Between CMI Quartiles and MAFLD Risk by Gender

Variables	Odds Ratio (95% CI)
	Crude	P-value	Model 1	P-value	Model 2	P-value
Males
CMI (Per SD increase)	4.34 (3.78–4.98)	<0.001	3.71 (3.19–4.30)	<0.001	2.72 (2.35–3.15)	<0.001
CMI (Quartile)
1th quartile	1.00 (ref.)		1.00 (ref.)		1.00 (ref.)
2th quartile	4.19 (3.26–5.40)	<0.001	4.06 (3.14–5.23)	<0.001	3.22 (2.47–4.20)	<0.001
3th quartile	12.35 (9.65–15.82)	<0.001	11.62 (9.01–14.99)	<0.001	8.35 (6.40–10.89)	<0.001
4st quartile	27.83 (21.51–36.01)	<0.001	24.70 (18.72–32.58)	<0.001	15.82 (11.84–21.14)	<0.001
P for trend	<0.001		<0.001		<0.001
Females
CMI (Per SD increase)	9.52 (6.88–13.17)	<0.001	6.09 (4.36–8.50)	<0.001	3.26 (2.36–4.51)	<0.001
CMI (Quartile)
1th quartile	1.00 (ref.)		1.00 (ref.)		1.00 (ref.)
2th quartile	3.08 (1.30–7.30)	0.011	2.58 (1.08–6.16)	<0.001	2.46 (0.95–6.37)	0.063
3th quartile	15.71 (7.22–34.20)	<0.001	10.94 (4.97–24.08)	<0.001	9.04 (3.77–21.69)	<0.001
4st quartile	61.11 (28.47–131.17)	<0.001	39.19 (18.05–85.10)	<0.001	22.60 (9.52–53.65)	<0.001
P for trend	<0.001		<0.001		<0.001

Notes: Model 1: adjusted for age, smoking, drinking, WC, BMI, WHtR, diabetes, hypertension and dyslipidemia. Model 2: adjusted for Model 1 plus AST, ALT, WBC, NE and LY.

Table 4 AUCs of Various Indexes for Discriminating MAFLD by Sex

Variables	AUC (95% CI)	Cut-Off Value	Sensitivity (%)	Specificity (%)	P-value
Males
CMI	0.796 (0.782–0.810)	0.86	76.9	69.9	<0.001
BMI (kg/m^2)	0.770 (0.756–0.785)	25.85	64.5	76.5	<0.001
WC (cm)	0.778 (0.763–0.792)	87.71	67.3	72.6	<0.001
WHtR	0.758 (0.743–0.773)	0.50	77.6	70.9	<0.001
TG (mmol/L)	0.758 (0.743–0.773)	1.55	72.0	68.1	<0.001
Females
CMI	0.853 (0.834–0.872)	0.41	82.8	75.2	<0.001
BMI (kg/m^2)	0.841 (0.821–0.861)	23.86	74.6	76.1	<0.001
WC (cm)	0.830 (0.808–0.852)	76.76	85.2	67.9	<0.001
WHtR	0.830 (0.808–0.851)	0.48	79.8	70.5	<0.001
TG (mmol/L)	0.818 (0.796–0.840)	1.05	84.2	65.6	<0.001

Figure 5 ROC curve comparison of obesity-related indices and TG in predicting MAFLD by sex.