Baseline characteristics in CAD and non-CAD group
Table 1 presents the clinical characteristics and laboratory parameters of 613 NAFLD patients (336 with CAD and 277 without CAD). Compared with non-CAD patients, CAD patients are older, more likely to be male and smokers, and have higher rates of diabetes and hypertension. Laboratory data shows that compared with non-CAD patients, CAD patients have higher ALT, AST. And the levels of Scr, TG, FPG and some inflammatory markers (WBC, MON, NEU) were higher, while the HDL-C of the CAD group was lower. On the other hand, the MHR, NHR, and NLR of CAD patients were higher than those of non-CAD patients (P < 0.05) (Fig. 1). There was no significant difference in BMI, TC, LDL-C, and LYM between the two groups (P > 0.05).
Table 1 Baseline characteristics of NAFLD patients with and without CAD.
|
CAD(n = 336)
|
non-CAD(n = 277)
|
P value
|
Age (Male)
|
57.67 ± 10.64
|
54.67 ± 9.87
|
< 0.001
|
Gender(years)
|
235(66.9)
|
137(49.5)
|
< 0.001
|
Smoke[(n%)]
|
184(54.8)
|
85(30.7)
|
< 0.001
|
HT[(n%)]
|
223(66.4)
|
119(43)
|
< 0.001
|
DM[(n%)]
|
115(34.2)
|
46(16.6)
|
< 0.001
|
BMI (kg/M2)
|
25.09(24.21,27.55)
|
25.64(24.69,27.34)
|
0.124
|
SBP (mmHg)
|
132.49 ± 19.41
|
130.51 ± 18.84
|
0.071
|
DBP (mmHg)
|
80.69 ± 13.21
|
79.46 ± 12.10
|
0.218
|
ALT(U/L)
|
28.30(18.60,40.75)
|
21.7(16.00,31.70)
|
< 0.001
|
AST(U/L)
|
24.7(19.20,35.50)
|
21.55(17.90,26.25)
|
< 0.001
|
Scr(mmol/L)
|
68.01 ± 15.94
|
64.30 ± 12.59
|
0.002
|
TC (mmol/L)
|
4.47 ± 1.14
|
4.49 ± 1.09
|
0.804
|
TG (mmol/L)
|
2.31 ± 1.77
|
1.83 ± 0.81
|
< 0.001
|
HDL-C(mmol/L)
|
1.08 ± 0.25
|
1.19 ± 0.27
|
< 0.001
|
LDL-C(mmol/L)
|
2.39 ± 0.71
|
2.38 ± 0.74
|
0.998
|
FPG (mmol/L)
|
5.86(5.03,7.29)
|
5.33(4.94,5.94)
|
< 0.001
|
WBC (109/L)
|
7.01(5.83,8.81)
|
6.02(5.15,7.54)
|
< 0.001
|
MON (109/L)
|
0.51 ± 0.16
|
0.44 ± 0.14
|
< 0.001
|
LYM (109/L)
|
1.81(1.46,2.26)
|
1.92(1.57,2.28)
|
0.149
|
NEU (109/L)
|
4.32(3.33,5.76)
|
3.44(2.72,4.66)
|
< 0.001
|
MHR
|
0.47(0.35,0.61)
|
0.37(0.27,0.48)
|
< 0.001
|
NHR
|
4.14(3.01,5.53)
|
2.89(2.22,4.09)
|
< 0.001
|
NLR
|
2.32(1.70,3.22)
|
1.78(1.37,2.53)
|
< 0.001
|
Values are expressed as mean ± standard deviation, no. (%), or median (interquartile range). P < 0.05 (two-sided) was defined as statistically significant. Bold values indicate statistically significance. |
CAD: coronary artery disease; BMI body mass index, HT hypertension, DM diabetes mellitus, SBP systolic blood pressure, DBP diastolic blood pressure, ALT alanine aminotransferase, AST aspartate aminotransferase, Cr creatinine, TC total cholesterol, TG triglycerides, HDL-C high-density lipoprotein cholesterol, LDL-C low-density lipoprotein cholesterol, FPG fasting plasma glucose, WBC white blood cell, MON monocytes, LYM lymphocytes, NEU neutrophils, MHR Monocyte-to-HDL-cholesterol ratio, NHR neutrophil-to- HDL-cholesterol ratio, NLR neutrophil-to-lymphocyte ratio. |
Logistic regression analysis of MHR, NHR and NLR in CAD and non-CAD patients
We used univariate and multivariate logistic regression to analyze the association between CAD and different inflammatory markers (Table 2). Whether in univariate analysis (Model 0) or after adjustment for age, sex, ALT, AST, Scr and FPG (Model 1), or further adjustment for smoking, history of hypertension and diabetes (Model 2), the levels of TG and HDL-C are all related to CAD. At the same time, we found that MHR (OR = 15.57, 95% CI: 4.68–51.85, p < 0.001), NHR (OR = 1.36, 95% CI: 1.21–1.53, p < 0.001), NLR (OR = 1.28, 95% CI: 1.09–1.49, p = 0.002) and log-transformed MHR (OR = 3.14, 95% CI: 1.84–5.38, p < 0.001) were independently associated with CAD (Table 2 and Fig. 2).
Table 2 Association between MHR, NHR NLR, and CAD in logistic regression Models.
|
Model 0
|
Model 1
|
Model 2
|
OR (95%CI)
|
P
|
OR (95%CI)
|
P
|
OR (95%CI)
|
P
|
TC (mmol/L)
|
0.98(0.85–1.13)
|
0.804
|
|
|
|
|
TG (mmol/L)
|
1.34(1.15–1.56)
|
< 0.001
|
1.27(1.07–1.51)
|
0.007
|
1.26(1.05–1.50)
|
0.012
|
HDL-C(mmol/L)
|
0.17(0.09–0.33)
|
< 0.001
|
0.17(0.08–0.38)
|
< 0.001
|
0.19(0.08–0.42)
|
< 0.001
|
LDL-C(mmol/L)
|
1.00(0.80–1.25)
|
0.998
|
|
|
|
|
WBC (109/L)
|
1.31(1.20–1.43)
|
< 0.001
|
1.25(1.13–1.38)
|
< 0.001
|
1.23(1.11–1.36)
|
< 0.001
|
MON (109/L)
|
17.04(5.59–51.94)
|
< 0.001
|
6.93(1.89–25.44)
|
0.004
|
5.43(1.42–20.80)
|
0.013
|
NEU (109/L)
|
1.40(1.26–1.55)
|
< 0.001
|
1.28(1.14–1.44)
|
< 0.001
|
1.28(1.13–1.43)
|
< 0.001
|
MHR
|
21.56(8.35–55.65)
|
< 0.001
|
18.42(5.69–59.65)
|
< 0.001
|
15.57(4.68–51.85)
|
< 0.001
|
NHR
|
1.47(1.33–1.64)
|
< 0.001
|
1.36(1.22–1.53)
|
< 0.001
|
1.36(1.21–1.53)
|
< 0.001
|
NLR
|
1.54(1.33–1.79)
|
< 0.001
|
1.24(1.07–1.43)
|
0.004
|
1.28(1.09–1.49)
|
0.002
|
LogMHR
|
4.08(2.69–6.18)
|
< 0.001
|
3.52(2.09–5.91)
|
< 0.001
|
3.14(1.84–5.38)
|
< 0.001
|
Model 0, non-adjusted model. |
Model I was adjusted for age, sex, ALT, AST, Scr and FPG. |
Model II was adjusted for age, sex, smoking history, hypertension, diabetes mellitus. |
ROC curve analysis of MHR, NHR, NLR and CAD
We further evaluated the performance of MHR, NHR, and NLR in predicting CAD by ROC curves (Fig. 3). The AUCs (95% CI) of MHR, NHR, and NLR were 0.660 (0.617–0.703), 0.683 (0.641–0.725), and 0.643 (0.600-0.687), respectively. After incorporating well-established risk factors (sex, age, smoking, hypertension, diabetes, TG, HDL-C, LDL-C), the AUCs of these models increased to 0.821, 0.830, and 0.828, respectively, greater than that of the original model.
Clinical and biochemical characteristics according to MHR tertiles
The study population was further divided according to MHR tertiles: Q1 (MHR ≤ 0.35, n = 204), Q2 (0.35 < MHR ≤ 0.51, n = 205), Q3 (MHR > 0.51, n = 204), as shown in the Table 3. Analysis of variance showed that the group with higher MHR had a lower age, a higher proportion of males and smoking, and among laboratory indicators, the high MHR group had ALT, AST, Scr, TG, HDL-C, WBC, MON, LYM, NEU, NHR, NLR was higher than the low-level MHR group, while TC and HDL-C were lower than the low-level MHR group. At the same time, the prevalence of CAD in the high-level MHR group was higher than that in the low-level MHR group (P < 0.001) (Fig. 4).
Table 3 Demographic and clinical characteristics of participants by MHR
|
Tertile 1
|
Tertile 2
|
Tertile 3
|
P
|
Age (Male)
|
58.22 ± 9.03
|
57.11 ± 10.52
|
53.61 ± 11.03
|
< 0.001
|
Gender(years)
|
71(34.8)
|
123(60.0)
|
178(87.3)
|
< 0.001
|
Smoke[(n%)]
|
40(19.6)
|
87(42.4)
|
142(69.6)
|
< 0.001
|
HT[(n%)]
|
110(23.9)
|
119(58.0)
|
113(55.4)
|
0.696
|
DM[(n%)]
|
46(22.5)
|
53(25.9)
|
62(30.4)
|
0.195
|
BMI (kg/M2)
|
25.24(23.84–27.04)
|
25.26(24.17–27.04)
|
25.95(24.82–28.28)
|
< 0.001
|
SBP (mmHg)
|
133.30 ± 17.84
|
131.39 ± 20.42
|
130.1 ± 19.08
|
0.236
|
DBP (mmHg)
|
79.58 ± 11.96
|
79.63 ± 13.10
|
81.19 ± 13.08
|
0.348
|
ALT(U/L)
|
22.20(16.30–32.80)
|
23.10(15.50-34.35)
|
30.30(20.03–41.05)
|
< 0.001
|
AST(U/L)
|
22.20(18.40–28.30)
|
21.25(17.40-27.95)
|
25.20(20.60–34.30)
|
< 0.001
|
Scr(mmol/L)
|
61.26 ± 12.14
|
65.08 ± 15.48
|
72.69 ± 13.74
|
< 0.001
|
TC (mmol/L)
|
4.65 ± 1.18
|
4.48 ± 1.01
|
4.23 ± 1.09
|
< 0.001
|
TG (mmol/L)
|
1.58(1.17–2.24)
|
1.75(1.30–2.35)
|
1.89(1.38–2.59)
|
0.001
|
HDL-C(mmol/L)
|
1.29 ± 0.25
|
1.10 ± 0.22
|
0.96 ± 0.20
|
< 0.001
|
LDL-C(mmol/L)
|
2.46 ± 0.75
|
2.39 ± 0.69
|
2.32 ± 0.72
|
0.152
|
FPG (mmol/L)
|
5.53(5.02–6.32)
|
5.54(4.98–6.46)
|
5.65(4.91–7.16)
|
0.685
|
WBC (109/L)
|
5.40(4.61–6.69)
|
6.62(5.68–7.63)
|
7.79(6.77–9.38)
|
< 0.001
|
MON (109/L)
|
0.34(0.28–0.40)
|
0.47(0.41–0.52)
|
0.61(0.53–0.72)
|
< 0.001
|
LYM (109/L)
|
1.70(1.42–2.08)
|
1.94(1.50–2.26)
|
2.00(1.61–2.49)
|
< 0.001
|
NEU (109/L)
|
2.96(2.51–4.03)
|
3.87(3.10–4.95)
|
4.86(3.82–6.24)
|
< 0.001
|
NHR
|
2.38(1.87–3.24)
|
3.52(2.74–4.40)
|
5.07(4.01–6.50)
|
< 0.001
|
NLR
|
1.75(1.34–2.53)
|
2.01(1.58–2.87)
|
2.47(1.74–3.24)
|
< 0.001
|
CAD[(n%)]
|
83(40.7)
|
110(53.7)
|
143(70.1)
|
< 0.001
|
Values are expressed as mean ± standard deviation, no. (%), or median (interquartile range). P < 0.05 (two-sided) was defined as statistically significant. |
Association between MHR and Gensini score.
The distribution of Gensini scores was examined according to grouping by MHR (Fig. 5). Chi-square test for trend showed that the high-level MHR group had a higher proportion of patients with very severe and severe stenosis, and the proportion of severe and very severe patients in the three groups increased with the increase of MHR (P < 0.05) (Fig. 5). Meanwhile, Table 4 illustrates the relationship between MHR and Gensini score. We set the MHR in the first tertile as the control group, and the OR value between MHR and different degrees of coronary stenosis was statistically significant. The ordered regression analysis showed that even after adjusting for common risk factors such as age, sex, and smoking the third tertile had a 2.95-fold higher risk of going up one step in the Gensini score grouping than the first tertile (OR = 2.95, 95% CI: 1.78–4.89, p < 0.001). However, when other classical risk factors were considered, the OR value of the second tertile became insignificant (OR = 1.31, 95% CI: 0.79–2.17, p = 0.298), and secondly, according to different Gensini scores After grouping, Kruskal–Wallis analysis showed that the MHR levels among different groups also showed an increasing trend (P < 0.001) (Fig. 6).
Table 4 Binary and ordinal regression analysis on the risk of Gensini score of NAFLD patients according to MHR
Gensini score = 0, non-CAD; 0 < Gensini score ≤ 25, mild coronary artery stenosis; 25 < Gensini score ≤ 50, moderate coronary artery stenosis; 50 < Gensini score ≤ 75, severe coronary artery stenosis; Gensini score > 75, very severe coronary artery stenosis. Adjusted: adjusted for gender, age, smoking.