The monocyte to high-density lipoprotein cholesterol ratio is positively associated with the severity of coronary artery disease in patients with nonalcoholic fatty liver disease

The monocyte to high-density lipoprotein cholesterol ratio is positively associated with the severity of coronary artery disease in patients with nonalcoholic fatty liver disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The monocyte to high-density lipoprotein cholesterol ratio is positively associated with the severity of coronary artery disease in patients with nonalcoholic fatty liver disease Yao Zhang, Leigang Wang, Jianqi Zhao, Lin Pang, Hongxuan Fan, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2198506/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for cardiovascular disease. Inflammation and dyslipidemia have been demonstrated to show excellent influence in atherosclerosis in patients with NAFLD. Monocyte (MON) and high-density lipoprotein cholesterol (HDL-C) ratio (MHR), one of the inflammation markers, is associated with the occurrence and severity of NAFLD. However, evidence of MHR in the risk of coronary artery disease (CAD) among NAFLD patients is limited. Methods We conducted a retrospective study of 612 patients with ultrasonogram-confirmed NAFLD who underwent percutaneous coronary intervention (PCI). All patients were divided into NAFLD + CAD group and NAFLD + non-CAD group. For univariate analysis between the two groups, continuous variables were compared using independent samples t-test or Mann-Whitney test, and categorical variables were compared using chi-square test or Fisher Exact tests. In addition, we used binary logistic regression analysis to identify risk and protective factors associated with CAD, constructed receiver operating characteristic (ROC) curves to assess the predictive value of MHR for CAD, and methodological studies of chi-square test for trend analysis the distribution of Gensini scores in MHR at different levels, and the risk degree of Gensini scores at different MHR levels by ordinal logistic regression. Results The study included a total of 336 CAD patients and 277 non-CAD patients. Univariate analysis showed that CAD patients had higher MHR than non-CAD patients (P < 0.001). Meanwhile, compared with pure NAFLD patients, multivariate logistic regression analysis showed that MHR remained to be an independent risk factor for CAD after adjusting for confounding risk factors (OR = 15.57, 95% CI 4.68–51.85, P < 0.001). At the same time, it was superior to traditional lipid parameters. NHR, NLR, and TG were also independent risk factors for CAD. HDL-C is a protective factor for CAD among NAFLD patients. The ROC curve showed that MHR or other inflammatory markers combined with traditional risk factors can improve the ability to predict CAD. In further study, trend chi-square showed that higher levels of MHR predicted more severe coronary lesions (P < 0.05). Multivariate ordinal logistic regression analysis showed that MHR was independently associated with changes in Gensini score (OR = 2.95, 95% CI 1.78–4.89, P < 0.001). Conclusion The MHR was positively associated with CAD risk among NAFLD patients and reflected coronary atherosclerosis severity. Monocyte to high-density lipoprotein cholesterol ratio Inflammation Non-alcoholic fatty liver disease Coronary artery disease Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in Western countries, affecting approximately 1.7 billion people worldwide, and its incidence and prevalence are increasing, resulting in a huge clinical and economic burden [ 1 ]. NAFLD may progress from pure steatosis (fat accumulation in ≥ 5% of hepatocytes) to necroinflammation and fibrosis, leading to nonalcoholic steatohepatitis (NASH) and, in some cases, cirrhosis, and even develop into hepatocellular carcinoma [ 2 , 3 ]. However, in NAFLD patients, cardiovascular disease (CVD) is currently thought to be the primary cause of mortality [ 4 ]. NAFLD is currently considered to be the liver manifestation of metabolic syndrome and an independent risk factor for CVD [ 5 ]. At present, many studies have demonstrated that NAFLD is associated with a high risk of CVD, independent on traditional cardiovascular risk factor [ 6 , 7 ]. Likewise, prevention and management of CVD risk factors in subjects with NAFLD can significantly reduce morbidity and mortality from CVD events [ 8 , 9 ]. So, it’s essential to identify and intervene high-risk CVD populations early in NAFLD. Chronic inflammation response plays a crucial role in the process of atherosclerosis in NAFLD patients [ 10 , 11 ]. Monocytes are not only one of the manufacturers of systemic inflammation but also a fundamental participant in the formation of atherosclerosis [ 12 ]. The entire process of monocyte proliferation, adhesion, infiltration into the vessel wall, and subsequent transformation into lipid-rich macrophages, has been well described in human and animal studies [ 13 ]. In addition, several studies have also demonstrated that the counts of monocytes and monocyte subsets are independent predictors of subclinical atherosclerosis or coronary artery disease (CAD) [ 14 , 15 ]. The monocyte to high-density lipoprotein cholesterol ratio (MHR) has drawn more attention recently as a quick indicator of oxidative stress and inflammation. MHR has been shown to be associated with many diseases, including acute ischemic Stroke (AIS), primary nephrotic syndrome (NS) and Parkinson's disease (PD) [ 16 – 18 ]. Meanwhile, a recent cross-sectional study has found that MHR is associated with the incidence of NAFLD [ 19 ], and that MHR is associated with a variety of cardiovascular events and has been shown to be positively associated with adverse cardiovascular outcomes [ 20 , 21 ]. However, data on the relationship between MHR and CAD risk in NAFLD patients are not yet available. In this study, we aimed to evaluate the association between the inflammatory biomarker MHR and CAD patients with NAFLD. Method Research population This study complies with the Declaration of Helsinki. The study protocol was approved by the local hospital ethics committee, and written informed consent was not required due to the retrospective study design. We performed a retrospective cross-sectional study of patients who underwent abdominal ultrasonography (US) and percutaneous coronary intervention (PCI) in the Department of Cardiology, Second Hospital of Shanxi Medical University from July 2021 to June 2022. We also excluded patients who met the following criteria: history of prior PCI or percutaneous transluminal coronary angioplasty (PTCA), history of alcohol consumption, secondary liver disease (e.g., viral hepatitis or autoimmune liver disease), structural heart disease (e.g., rheumatic heart disease, cardiomyopathy), renal disease or end-stage renal disease (ESRD), infectious disease, acute infection within 2 weeks or history of malignancy, incomplete medical records. Finally, 613 patients were included in the study. Clinical and Laboratory Data Patient demographics such as age and gender; smoking history and history of diabetes and hypertension were obtained from electronic medical records. Laboratory data were obtained on admission, including blood cell count levels (white blood cell, neutrophils, lymphocytes, monocytes); liver biochemistry (alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels); fasting plasma glucose (FPG), serum creatinine (Scr), total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). MHR is one of the inflammatory markers and is calculated as the ratio of monocytes (MON) to high-density lipoprotein cholesterol (HDL-C), NLR is calculated as the ratio of neutrophils (NEU) to lymphocytes (LYM), and NHR is calculated as the ratio of neutrophils (NEU) to high-density lipoprotein cholesterol (HDL-C) was calculated, and its levels were obtained from the same blood sample. Assessment of CAD Severity CAD is defined as ≥ 50% occlusion of at least one major coronary artery, including the left main coronary artery (LM), left anterior descending artery (LAD), left circumflex coronary artery (LCX) and right coronary artery (RCA), or coronary artery other major branches of blood vessels. The severity of coronary atherosclerosis was assessed according to the Gensini score, which was as follows: <25% obstruction 1 point, 26%-50% obstruction 2 points, 51%-75% stenosis 4 points, 76%-90% stenosis 8 32 points for complete occlusion. Each lesion score is multiplied by the lesion vessel score, which is based on the importance of the lesion's location in the coronary circulation, (5 for LM; 2.5 for proximal LAD and LCX; 1.5 for mid LAD; RCA 1.0 for any segment, distal segment of LAD and LCX, first diagonal artery, posterolateral artery and blunt marginal artery (OM); and 0.5 for other segments). All CAD patients were divided into 4 groups according to Gensini score, including mild stenosis (Gensini score ≤ 25), moderate stenosis (25 < Gensini score ≤ 50), severe stenosis (50 75), and we defined Gensini score = 0 for all non-CAD patients. Statistical analysis: Statistical analysis was performed using SPSS version 26.0 software and R version 4.0.1 software. Continuous variables were expressed as mean ± standard deviation (SD) or median (IQR) and were compared between groups of patients with or without CAD. Categorical variables are expressed as percentages. For univariate analysis between CAD and non-CAD, the independent samples t-test or Mann-Whitney test was used for comparison of continuous variables, and the chi-square test or Fisher's exact test was used for comparison between categorical variables. Binary logistic regression analysis was performed to identify independent factors associated with CAD, and variables with p-values less than 0.05 in the univariate logistic regression analysis were included in the multivariate logistic regression analysis. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive value of MHR for CAD, chi-square test for trend analysis between multiple groups of categorical variables, Kruskal–Wallis test analysis between multiple groups of continuous variables, and ordinal logistic regression analysis The degree of risk of different MHR levels between different Gensini score groups. P < 0.05 (two-sided) was considered statistically significant. Result 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). 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/M 2 ) 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 (10 9 /L) 7.01(5.83,8.81) 6.02(5.15,7.54) < 0.001 MON (10 9 /L) 0.51 ± 0.16 0.44 ± 0.14 < 0.001 LYM (10 9 /L) 1.81(1.46,2.26) 1.92(1.57,2.28) 0.149 NEU (10 9 /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 (10 9 /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 (10 9 /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 (10 9 /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 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/M 2 ) 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 (10 9 /L) 5.40(4.61–6.69) 6.62(5.68–7.63) 7.79(6.77–9.38) < 0.001 MON (10 9 /L) 0.34(0.28–0.40) 0.47(0.41–0.52) 0.61(0.53–0.72) < 0.001 LYM (10 9 /L) 1.70(1.42–2.08) 1.94(1.50–2.26) 2.00(1.61–2.49) < 0.001 NEU (10 9 /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 75, very severe coronary artery stenosis. Adjusted: adjusted for gender, age, smoking. Discussion As a novel and simple measure, MHR represents the balance of anti-inflammatory and pro-inflammatory. In the present study, we used coronary angiography to describe the presence of coronary stenosis and assessed the severity of CAD by the Gensini score. We demonstrated that MHR is an independent predictor of CAD in NAFLD patients despite adjusting for traditional CAD risk factors such as age, sex, smoking history, hypertension and diabetes. We also found that MHR was positively association with the severity of CAD in NAFLD patients. MHR, as a novel inflammatory biomarker, plays an important role in the emergence of CAD in NAFLD patients. Hence, MHR may prove to be a useful tool for predicting the existence and severity of CAD in NAFLD patients in clinical practice. As the central factor of inflammation, monocytes have been proved to play an important role in the progression of NAFLD [ 22 ]. Monocytes and the macrophages they give rise to are a significant source of various inflammatory factors in the liver, contributing significantly to the development of NAFLD [ 23 ]. Currently, it is believed that classical monocytes (CD14 + + CD16-) make up about 85% of all monocytes, non-classical monocytes (CD14 + CD16++) make up 10%, and intermediate monocyte nuclear cells (CD14 + + CD16+) make up 5% of the total monocyte count. But intermediate monocytes are the most unstable, preferentially mobilized in an inflammatory environment and regulated the progression of liver fibrosis [ 24 ]. The data of Zhang et al. [ 25 ] also demonstrated that an increase in the fraction of intermediate monocytes and a decrease in the fraction of classical monocytes were independently associated with NAFLD. These intermediate monocytes typically pass through CCL2, CCL5, and CXCL10 during inflammation recruited to the liver [ 26 – 28 ]. And differentiated into macrophages with dual pro-inflammatory and pro-fibrotic properties, which further contribute to liver fibrosis by activating hepatic stellate cells [ 23 , 29 ]. Second, monocytes also have a special role in atherosclerosis [ 30 ]. Upon activation, monocytes migrate into the subendothelium by adhering to the adhesion factors expressed by the damaged vascular endothelium [ 31 ]. These macrophages are then transformed into foam cells by engulfing oxidized LDL-C, and they release pro-inflammatory and pro-oxidative cytokines that draw T lymphocytes and other monocytes to the site of inflammation [ 32 ]. The function of macrophages in the artery wall is only one aspect of monocytes' atherogenic impact. Many soluble factors associated with atherosclerosis could also activate circulating monocytes [ 33 ], suggesting that circulating monocytes can participate in the development and progression of CAD by triggering inflammation. Additionally, tissue factor can be expressed by circulating monocytes in an inflammatory or prothrombotic condition, resulting in a procoagulant phenotype [ 34 ], which promotes the growth of atherosclerosis. High-density lipoprotein (HDL-C), an anti-atherosclerotic factor, has been shown to have multiple biological activities, including reversal of cholesterol transport, anti-oxidative, anti-inflammatory, anti-apoptotic, anti-thrombotic and anti-atherosclerotic effects [ 35 , 36 ]. It was demonstrated that HDL not only reduces monocyte recruitment to the arterial wall by decreasing the f-actin content of monocytes, but also reduces the expression of CD11b on monocyte and endothelial adhesion molecules and inhibits monocyte adhesion to the endothelium [ 37 ], thus controlling the proliferation and activation of monocytes; achieving protection of endothelial cells from inflammation and oxidative stress [ 38 ]. Second, prior studies have noted that HDL-C, an anti-atherosclerotic lipoprotein, can inhibit monocyte tissue factor expression by preventing p38 activation and phosphoinositide 3-kinase inhibition [ 39 ]. Furthermore, HDL-C molecules have the ability to counteract macrophage migration and eliminate cholesterol in macrophages [ 40 ]. In conclusion, HDL-C may inhibit the development of atherosclerosis through the inhibition of monocytes. Therefore, inflammation may be a bridge factor for NAFLD patients with high CAD risk. And monocytes and HDL-C may have distinct functions in the progression or inhibition of arteriosclerosis in NAFLD patients. A model constructed using these two predictors, the emerging monocytes to HDL ratio (MHR) may be a better marker for assessing the development and progression of atherosclerosis in NAFLD patients. At present, a strong relationship between MHR and cardiovascular disease has been reported in the literature. Li et al [ 41 ] proved that elevated MHR levels are associated with in-hospital MACE and long-term bleeding events in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients undergoing PCI. A meta-analysis of 11,345 CHD patients included 9 studies [ 42 ] showed that high levels of MHR may be associated with higher long-term mortality and long-term MACE in CHD patients. In addition, MHR currently not only related to CVD. Huang et al [ 19 ] found that MHR was also an independent factor for NAFLD through a cross-sectional study, and a high MHR predicted a high risk of NAFLD. However, in reviewing the literature, no data was found on the association between MHR and CAD risk in NAFLD patients. Therefore, the present study was designed to determine the effect of MHR. This study also has several limitations. Firstly, this is a single-center retrospective study, including a small sample size, lack of follow-up data, and cannot prove the causal and prognostic relationship between MHR and CAD. Therefore, our findings need to be confirmed in other large prospective studies with long-term clinical follow-up. Secondly, the diagnosis of NAFLD is made by ultrasound examination. Ultrasound is not the most sensitive method for diagnosing fatty liver, and there are some false positives. However, due to the advantages of simplicity, convenience, and repeatability, ultrasound is still the most effective clinical diagnosis methods of NAFLD at present. Thirdly, due to the inability to accurately obtain a drinking history and to accurately define alcoholic fatty liver versus nonalcoholic fatty liver, we excluded patients with a previous drinking history when collecting participants, which may have resulted in a reduced sample size. Finally, because this study uses blood lipid indicators, patients who have previously received oral lipid-lowering medication were not excluded due to sample size issues, which could have affected some patients' LDL-C levels after taking the medication and resulted in different LDL-C levels between CAD patients and non-CAD patients. In conclusion, further studies are needed to investigate and validate the underlying mechanisms of the association between MHR levels and CVD in NAFLD patients. Conclusion The results of this study indicate that MHR in NAFLD patients with CAD was significantly higher than without CAD, and MHR was positively associated with the severity of CAD. MHR, as a simple and feasible inflammatory parameter, could be used to predict CAD risk in NAFLD patients in clinical practice. So, this indicator should be given more attention in the workup of NAFLD patients. Abbreviations ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CAD: Coronary artery disease; CVD: Cardiovascular disease; DBP: Diastolic blood pressure; DM: Diabetes mellitus; FBG fasting blood glucose; HDL-C: High density lipoprotein cholesterol; HT: Hypertension; LDL-C: Low-density lipoprotein cholesterol; LYM: lymphocytes; MON: Monocyte; MHR: monocyte to high-density lipoprotein cholesterol ratio; NAFLD: Non-alcoholic fatty liver disease; NEU: neutrophils; Scr: Serum creatinine; NHR: neutrophil-to- HDL-cholesterol ratio; NLR: neutrophil-to-lymphocyte ratio; TC: Total cholesterol; TG: Triglyceride. Declarations Ethics approval and consent to participate The study was approved by the Medical Ethics Committee of Shanxi Medical University, which waived the need for written informed consent due to the retrospective study design. Consent for publication Not applicable. Date Availability The original contributions of this study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author. Competing interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest. Funding This work was supported by the National Natural Science Foundation of China (Grant No. 81970391), “Four a batch of” talent of Shanxi Province (2021RC08), and the Excellent Youth Foundation of Shanxi Province (Grant Number 201901D211504). Author contributions YZ and BL: study design; YZ and LW: data analysis; LP, LW, and JZ: manuscript drafting; YZ, LW, and JZ: data collection; LW, HF, and WZ: manuscript revision; BL: review and final approval. All authors read and approved the final manuscript. Acknowledgments We sincerely thank the arrhythmia team of the Second Hospital of Shanxi Medical University for supporting our work. References Powell EE, Wong VW, Rinella M. Non-alcoholic fatty liver disease. The Lancet. 2021;397(10290):2212-24. Satapathy S, Sanyal A. Epidemiology and natural history of nonalcoholic fatty liver disease. Semin Liver Dis. 2015;35(03):221-35. Masarone M, Federico A, Abenavoli L, Loguercio C, Persico M. Non alcoholic fatty liver: epidemiology and natural history. Rev Recent Clin Trials. 2014 2014;9(3):126-33. Targher G, Byrne CD, Tilg H. Nafld and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications. Gut. 2021;69(9):1691-705. Byrne CD, Targher G. Nafld: a multisystem disease. J Hepatol. 2015 2015 Apr;62(1 Suppl):S47-64. Targher G, Corey KE, Byrne CD. Nafld, and cardiovascular and cardiac diseases: factors influencing risk, prediction and treatment. Diabetes Metab. 2021 2021 Mar;47(2):101215. Targher G, Byrne CD, Tilg H. Nafld and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications. Gut. 2020 2020 Sep;69(9):1691-705. Adams LA, Anstee QM, Tilg H, Targher G. Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases. Gut. 2017 2017 Jun;66(6):1138-53. Wang Z, Ye M, Zhang XJ, Zhang P, Cai J, Li H, et al. Impact of nafld and its pharmacotherapy on lipid profile and cvd. Atherosclerosis. 2022 2022 Aug; 355:30-44. Bhatia LS, Curzen NP, Calder PC, Byrne CD. Non-alcoholic fatty liver disease: a new and important cardiovascular risk factor? Eur Heart J. 2012;33(10):1190-200. Askin L., Tanriverdi O., Tibilli H., and Turkmen S., Associations between Vaspin Levels and Coronary Artery Disease. Cardiovasc Innov Appl 2019;4(3): 211-216. Marchio P, Guerra-Ojeda S, Vila JM, Aldasoro M, Victor VM, Mauricio MD. Targeting early atherosclerosis: a focus on oxidative stress and inflammation. Oxid Med Cell Longev. 2019 2019; 2019:8563845. Moore KJ, Sheedy FJ, Fisher EA. Macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol. 2013 2013 Oct;13(10):709-21. Oh ES, Na M, Rogers CJ. The association between monocyte subsets and cardiometabolic disorders/cardiovascular disease: a systematic review and meta-analysis. Front Cardiovasc Med. 2021 2021; 8:640124. Rogacev KS, Cremers B, Zawada AM, Seiler S, Binder N, Ege P, et al. Cd14++cd16+ monocytes independently predict cardiovascular events: a cohort study of 951 patients referred for elective coronary angiography. J Am Coll Cardiol. 2012 2012 Oct 16;60(16):1512-20. Liu Z, Fan Q, Wu S, Wan Y, Lei Y. Compared with the monocyte to high-density lipoprotein ratio (mhr) and the neutrophil to lymphocyte ratio (nlr), the neutrophil to high-density lipoprotein ratio (nhr) is more valuable for assessing the inflammatory process in parkinson's disease. Lipids Health Dis. 2021 2021 Apr 19;20(1):35. Omar T, Karakayalı M, Yesin M, Alaydın HC, Karabağ Y, Gümüşdağ A. Monocyte to high-density lipoprotein cholesterol ratio is associated with the presence of carotid artery disease in acute ischemic stroke. Biomark Med. 2021 2021 May;15(7):489-95. Yılmaz AF, Eynel E, Oruç 0, Ince H, Yüksel E, Aydın E. The role of monocyte to high-density lipoprotein cholesterol ratio in predicting the severity of proteinuria and renal dysfunction in primary nephrotic syndrome. Cureus. 2021 2021 Dec;13(12): e20345. Huang H, Wang Q, Shi X, Chen Y, Shen C, Zhang J, et al. Association between monocyte to high-density lipoprotein cholesterol ratio and nonalcoholic fatty liver disease: a cross-sectional study. Mediators Inflamm. 2021 2021; 2021:6642246. Ganjali S, Gotto AJ, Ruscica M, Atkin SL, Butler AE, Banach M, et al. Monocyte-to-hdl-cholesterol ratio as a prognostic marker in cardiovascular diseases. J Cell Physiol. 2018 2018 Dec;233(12):9237-46. Yu R, Hou R, Wang T, Li T, Han H, An J. Correlation between monocyte to high-density lipoprotein ratio and major adverse cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention. Pak J Med Sci. 2021 2021 May-Jun;37(3):885-89. Tacke F, Zimmermann HW. Macrophage heterogeneity in liver injury and fibrosis. J Hepatol. 2014 2014 May;60(5):1090-96. Hammoutene A, Rautou PE. Role of liver sinusoidal endothelial cells in non-alcoholic fatty liver disease. J Hepatol. 2019 2019 Jun;70(6):1278-91. Mukherjee R, Kanti BP, Kumar TP, Tripathy R, Kumar DB, Ravindran B. Non-classical monocytes display inflammatory features: validation in sepsis and systemic lupus erythematous. Sci Rep. 2015 2015 Sep 11; 5:13886. Zhang X, Shen J, Man K, Chu ES, Yau TO, Sung JC, et al. Cxcl10 plays a key role as an inflammatory mediator and a non-invasive biomarker of non-alcoholic steatohepatitis. J Hepatol. 2014 2014 Dec;61(6):1365-75. Baeck C, Wehr A, Karlmark KR, Heymann F, Vucur M, Gassler N, et al. Pharmacological inhibition of the chemokine ccl2 (mcp-1) diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury. Gut. 2012 2012 Mar;61(3):416-26. Miura K, Yang L, van Rooijen N, Ohnishi H, Seki E. Hepatic recruitment of macrophages promotes nonalcoholic steatohepatitis through ccr2. Am J Physiol Gastrointest Liver Physiol. 2012 2012 Jun 1;302(11): G1310-21. Zimmermann HW, Seidler S, Nattermann J, Gassler N, Hellerbrand C, Zernecke A, et al. Functional contribution of elevated circulating and hepatic non-classical cd14cd16 monocytes to inflammation and human liver fibrosis. Plos One. 2010 2010 Jun 10;5(6): e11049 Karlmark KR, Weiskirchen R, Zimmermann HW, Gassler N, Ginhoux F, Weber C, et al. Hepatic recruitment of the inflammatory gr1+ monocyte subset upon liver injury promotes hepatic fibrosis. Hepatology. 2009 2009 Jul;50(1):261-74. Maiwald S, Zwetsloot PP, Sivapalaratnam S, Dallinga-Thie GM. Monocyte gene expression and coronary artery disease. Curr Opin Clin Nutr Metab Care. 2013 2013 Jul;16(4):411-17. Tani S, Matsumoto M, Anazawa T, Kawamata H, Furuya S, Takahashi H, et al. Development of a model for prediction of coronary atherosclerotic regression: evaluation of high-density lipoprotein cholesterol level and peripheral blood monocyte count. Heart Vessels. 2012 2012 Mar;27(2):143-50 Açıkgöz SK, Açıkgöz E, Şensoy B, Topal S, Aydoğdu S. Monocyte to high-density lipoprotein cholesterol ratio is predictive of in-hospital and five-year mortality in st-segment elevation myocardial infarction. Cardiol J. 2016 2016;23(5):505-12. Gratchev A, Sobenin I, Orekhov A, Kzhyshkowska J. Monocytes as a diagnostic marker of cardiovascular diseases. Immunobiology. 2012 2012 May;217(5):476-82. Ganjali S, Gotto AJ, Ruscica M, Atkin SL, Butler AE, Banach M, et al. Monocyte-to-hdl-cholesterol ratio as a prognostic marker in cardiovascular diseases. J Cell Physiol. 2018 2018 Dec;233(12):9237-46. Gomaraschi M, Basilico N, Sisto F, Taramelli D, Eligini S, Colli S, et al. High-density lipoproteins attenuate interleukin-6 production in endothelial cells exposed to pro-inflammatory stimuli. Biochim Biophys Acta. 2005 2005 Sep 15;1736(2):136-43. Ganjali S, Momtazi AA, Banach M, Kovanen PT, Stein EA, Sahebkar A. Hdl abnormalities in familial hypercholesterolemia: focus on biological functions. Prog Lipid Res. 2017 2017 Jul; 67:16-26. Murphy AJ, Woollard KJ, Hoang A, Mukhamedova N, Stirzaker RA, McCormick SP, et al. High-density lipoprotein reduces the human monocyte inflammatory response. Arterioscler Thromb Vasc Biol. 2008 2008 Nov;28(11):2071-77. Kundi H, Kiziltunc E, Cetin M, Cicekcioglu H, Cetin ZG, Cicek G, et al. Association of monocyte/hdl-c ratio with syntax scores in patients with stable coronary artery disease. Herz. 2016 2016 Sep;41(6):523-29. Ossoli A, Remaley AT, Vaisman B, Calabresi L, Gomaraschi M. Plasma-derived and synthetic high-density lipoprotein inhibit tissue factor in endothelial cells and monocytes. Biochem J. 2016 2016 Jan 15;473(2):211-19. Usta A, Avci E, Bulbul CB, Kadi H, Adali E. The monocyte counts to hdl cholesterol ratio in obese and lean patients with polycystic ovary syndrome. Reprod Biol Endocrinol. 2018 2018 Apr 10;16(1):34. Li C, Fan H, Liu Y, Zeng L, Chen P, Duan C, et al. The monocyte to high-density lipoprotein cholesterol ratio and outcomes in type 2 diabetes mellitus patients with non-st-segment elevation acute coronary syndrome. Ann Transl Med. 2021 2021 Nov;9(21):1627. Liu HT, Jiang ZH, Yang ZB, Quan XQ. Monocyte to high-density lipoprotein ratio predict long-term clinical outcomes in patients with coronary heart disease: a meta-analysis of 9 studies. Medicine (Baltimore). 2022 2022 Aug 19;101(33): e30109. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2198506","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":147455805,"identity":"98a5cd39-4b0d-44b8-beac-848cd69ffa63","order_by":0,"name":"Yao Zhang","email":"","orcid":"","institution":"Shanxi Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yao","middleName":"","lastName":"Zhang","suffix":""},{"id":147455806,"identity":"0935e246-ccce-4f29-9d6f-cf6b564e5bc9","order_by":1,"name":"Leigang Wang","email":"","orcid":"","institution":"Shanxi Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Leigang","middleName":"","lastName":"Wang","suffix":""},{"id":147455807,"identity":"5dcf79ec-484b-447a-bfd5-84d10eb8dfba","order_by":2,"name":"Jianqi Zhao","email":"","orcid":"","institution":"Shanxi Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jianqi","middleName":"","lastName":"Zhao","suffix":""},{"id":147455808,"identity":"627f2d05-6b87-41c8-b23a-12215e609819","order_by":3,"name":"Lin Pang","email":"","orcid":"","institution":"Shanxi Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lin","middleName":"","lastName":"Pang","suffix":""},{"id":147455809,"identity":"112f7ec0-eab5-4a12-aec3-ab221c2e44cd","order_by":4,"name":"Hongxuan Fan","email":"","orcid":"","institution":"Shanxi Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hongxuan","middleName":"","lastName":"Fan","suffix":""},{"id":147455810,"identity":"d7c85da4-5cc9-4634-9b2a-44b1f7cff17e","order_by":5,"name":"Wenjing Zhang","email":"","orcid":"","institution":"Shanxi Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Wenjing","middleName":"","lastName":"Zhang","suffix":""},{"id":147455811,"identity":"9cec5b6f-49c3-4210-b2e4-5563155aa9df","order_by":6,"name":"Bin Liang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0klEQVRIiWNgGAWjYFAC5oYDQDKBjYH5wIEPP4jQwMPACNPClnhwZg+RWkB0ApBpfJiDjQgt9hKJjQd+7qjN45Pu+XAYaII8v9gBArZIJDYc7D1zvJhN5uyGwwUWDIYzZycQ1nKAt+1YYptE7obDM3gYEgxuE6Hl4F+wlpwHh3nYiNRymLetBqSFgUgtZx42HJZtO1DMJpFmAAxkCcJ+YW9PPvzxbVtdnvyM5McfPvywkeeXJqCFQQCs4DCMK0FAOQjwHwCRdUSoHAWjYBSMghELAPjISy4Xk2EtAAAAAElFTkSuQmCC","orcid":"","institution":"Second Hospital of Shanxi Medical University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Bin","middleName":"","lastName":"Liang","suffix":""}],"badges":[],"createdAt":"2022-10-24 12:14:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2198506/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2198506/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":28531011,"identity":"f57e4c51-d261-44b9-a7f9-8914336ab016","added_by":"auto","created_at":"2022-11-01 19:23:46","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":33725,"visible":true,"origin":"","legend":"\u003cp\u003eInflammatory characteristics of patients in CAD and non-CAD groups.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-2198506/v1/e5b2da86f2ce5ac98148dbdf.png"},{"id":28531015,"identity":"986d6416-d876-415c-aa98-0df6d1a4d6d6","added_by":"auto","created_at":"2022-11-01 19:23:46","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":373998,"visible":true,"origin":"","legend":"\u003cp\u003eForest plots of independent factors associated with CAD in NAFLD\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-2198506/v1/af32c6e9e891fe9c5a0363d7.png"},{"id":28531518,"identity":"14d08ee6-3aaf-4ca7-8135-874a9a21af65","added_by":"auto","created_at":"2022-11-01 19:28:46","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":116887,"visible":true,"origin":"","legend":"\u003cp\u003eReceiver operating characteristic (ROC) curve analysis of the predictive power of MHR，NHR, and NLR for CAD. MHR Model, NHR Model, NLR Model: new Models integrating recognized risk factors for CAD (Gender, Age, Smoking, HT, DM, TG, HDL-C, LDL-C).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-2198506/v1/7acddc145346be40490e6746.png"},{"id":28531016,"identity":"f117bd9c-2f4a-4cbe-9da8-dc4698df37ca","added_by":"auto","created_at":"2022-11-01 19:23:46","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":265874,"visible":true,"origin":"","legend":"\u003cp\u003ePrevalence of CAD in patients with NAFLD at the ratio of Monocytes to HDL cholesterol (MHR) at different tertiles.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-2198506/v1/d060ae12fa1539dc5b9fcb58.png"},{"id":28531014,"identity":"5a7430fc-b890-4327-b607-9c921a5bab15","added_by":"auto","created_at":"2022-11-01 19:23:46","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":329022,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of Gensini score of the ratio of Monocyte to HDL cholesterol (MHR) in different tertile of NAFLD patients\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-2198506/v1/f456182f91acfa6fd8ced151.png"},{"id":28531013,"identity":"28220f19-2410-4d6a-8bec-326912a15827","added_by":"auto","created_at":"2022-11-01 19:23:46","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":386830,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of MHR According to Gensini Score.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-2198506/v1/6098b1d361d8ace9b3878b43.png"},{"id":33860397,"identity":"e31c6298-3608-42da-b5cd-837958807713","added_by":"auto","created_at":"2023-03-06 20:44:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":894454,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2198506/v1/9619498e-dc7f-4e23-bd45-326e87788108.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The monocyte to high-density lipoprotein cholesterol ratio is positively associated with the severity of coronary artery disease in patients with nonalcoholic fatty liver disease","fulltext":[{"header":"Introduction","content":"\u003cp\u003eNon-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in Western countries, affecting approximately 1.7\u0026nbsp;billion people worldwide, and its incidence and prevalence are increasing, resulting in a huge clinical and economic burden [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNAFLD may progress from pure steatosis (fat accumulation in \u0026ge;\u0026thinsp;5% of hepatocytes) to necroinflammation and fibrosis, leading to nonalcoholic steatohepatitis (NASH) and, in some cases, cirrhosis, and even develop into hepatocellular carcinoma [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, in NAFLD patients, cardiovascular disease (CVD) is currently thought to be the primary cause of mortality [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNAFLD is currently considered to be the liver manifestation of metabolic syndrome and an independent risk factor for CVD [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. At present, many studies have demonstrated that NAFLD is associated with a high risk of CVD, independent on traditional cardiovascular risk factor [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Likewise, prevention and management of CVD risk factors in subjects with NAFLD can significantly reduce morbidity and mortality from CVD events [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. So, it\u0026rsquo;s essential to identify and intervene high-risk CVD populations early in NAFLD.\u003c/p\u003e \u003cp\u003eChronic inflammation response plays a crucial role in the process of atherosclerosis in NAFLD patients [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Monocytes are not only one of the manufacturers of systemic inflammation but also a fundamental participant in the formation of atherosclerosis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The entire process of monocyte proliferation, adhesion, infiltration into the vessel wall, and subsequent transformation into lipid-rich macrophages, has been well described in human and animal studies [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In addition, several studies have also demonstrated that the counts of monocytes and monocyte subsets are independent predictors of subclinical atherosclerosis or coronary artery disease (CAD) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe monocyte to high-density lipoprotein cholesterol ratio (MHR) has drawn more attention recently as a quick indicator of oxidative stress and inflammation. MHR has been shown to be associated with many diseases, including acute ischemic Stroke (AIS), primary nephrotic syndrome (NS) and Parkinson's disease (PD) [\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Meanwhile, a recent cross-sectional study has found that MHR is associated with the incidence of NAFLD [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], and that MHR is associated with a variety of cardiovascular events and has been shown to be positively associated with adverse cardiovascular outcomes [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. However, data on the relationship between MHR and CAD risk in NAFLD patients are not yet available. In this study, we aimed to evaluate the association between the inflammatory biomarker MHR and CAD patients with NAFLD.\u003c/p\u003e"},{"header":"Method","content":"\u003ch2\u003eResearch population\u003c/h2\u003e\n\u003cp\u003eThis study complies with the Declaration of Helsinki. The study protocol was approved by the local hospital ethics committee, and written informed consent was not required due to the retrospective study design.\u003c/p\u003e\n\u003cp\u003eWe performed a retrospective cross-sectional study of patients who underwent abdominal ultrasonography (US) and percutaneous coronary intervention (PCI) in the Department of Cardiology, Second Hospital of Shanxi Medical University from July 2021 to June 2022. We also excluded patients who met the following criteria: history of prior PCI or percutaneous transluminal coronary angioplasty (PTCA), history of alcohol consumption, secondary liver disease (e.g., viral hepatitis or autoimmune liver disease), structural heart disease (e.g., rheumatic heart disease, cardiomyopathy), renal disease or end-stage renal disease (ESRD), infectious disease, acute infection within 2 weeks or history of malignancy, incomplete medical records. Finally, 613 patients were included in the study.\u003c/p\u003e\n\u003ch2\u003eClinical and Laboratory Data\u003c/h2\u003e\n\u003cp\u003ePatient demographics such as age and gender; smoking history and history of diabetes and hypertension were obtained from electronic medical records. Laboratory data were obtained on admission, including blood cell count levels (white blood cell, neutrophils, lymphocytes, monocytes); liver biochemistry (alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels); fasting plasma glucose (FPG), serum creatinine (Scr), total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). MHR is one of the inflammatory markers and is calculated as the ratio of monocytes (MON) to high-density lipoprotein cholesterol (HDL-C), NLR is calculated as the ratio of neutrophils (NEU) to lymphocytes (LYM), and NHR is calculated as the ratio of neutrophils (NEU) to high-density lipoprotein cholesterol (HDL-C) was calculated, and its levels were obtained from the same blood sample.\u003c/p\u003e\n\u003ch2\u003eAssessment of CAD Severity\u003c/h2\u003e\n\u003cp\u003eCAD is defined as \u0026ge;\u0026thinsp;50% occlusion of at least one major coronary artery, including the left main coronary artery (LM), left anterior descending artery (LAD), left circumflex coronary artery (LCX) and right coronary artery (RCA), or coronary artery other major branches of blood vessels. The severity of coronary atherosclerosis was assessed according to the Gensini score, which was as follows: \u0026lt;25% obstruction 1 point, 26%-50% obstruction 2 points, 51%-75% stenosis 4 points, 76%-90% stenosis 8 32 points for complete occlusion. Each lesion score is multiplied by the lesion vessel score, which is based on the importance of the lesion\u0026apos;s location in the coronary circulation, (5 for LM; 2.5 for proximal LAD and LCX; 1.5 for mid LAD; RCA 1.0 for any segment, distal segment of LAD and LCX, first diagonal artery, posterolateral artery and blunt marginal artery (OM); and 0.5 for other segments). All CAD patients were divided into 4 groups according to Gensini score, including mild stenosis (Gensini score\u0026thinsp;\u0026le;\u0026thinsp;25), moderate stenosis (25\u0026thinsp;\u0026lt;\u0026thinsp;Gensini score\u0026thinsp;\u0026le;\u0026thinsp;50), severe stenosis (50\u0026thinsp;\u0026lt;\u0026thinsp;Gensini score\u0026thinsp;\u0026le;\u0026thinsp;75), very severe stenosis (Gensini score\u0026thinsp;\u0026gt;\u0026thinsp;75), and we defined Gensini score\u0026thinsp;=\u0026thinsp;0 for all non-CAD patients.\u003c/p\u003e\n\u003cdiv class=\"Section2\" id=\"Sec3\"\u003e\n \u003ch2\u003eStatistical analysis:\u003c/h2\u003e\n \u003cp\u003eStatistical analysis was performed using SPSS version 26.0 software and R version 4.0.1 software. Continuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) or median (IQR) and were compared between groups of patients with or without CAD. Categorical variables are expressed as percentages. For univariate analysis between CAD and non-CAD, the independent samples t-test or Mann-Whitney test was used for comparison of continuous variables, and the chi-square test or Fisher\u0026apos;s exact test was used for comparison between categorical variables. Binary logistic regression analysis was performed to identify independent factors associated with CAD, and variables with p-values less than 0.05 in the univariate logistic regression analysis were included in the multivariate logistic regression analysis. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive value of MHR for CAD, chi-square test for trend analysis between multiple groups of categorical variables, Kruskal\u0026ndash;Wallis test analysis between multiple groups of continuous variables, and ordinal logistic regression analysis The degree of risk of different MHR levels between different Gensini score groups. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 (two-sided) was considered statistically significant.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Result","content":"\u003ch2\u003eBaseline characteristics in CAD and non-CAD group\u003c/h2\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e 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 \u0026lt; 0.05) (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). There was no significant difference in BMI, TC, LDL-C, and LYM between the two groups (P \u0026gt; 0.05).\u003c/p\u003e\n\u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003ccaption language=\"En\"\u003eTable 1\u0026nbsp;\u003cp\u003eBaseline characteristics of NAFLD patients with and without CAD.\u003c/p\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth\u003e\u003cbr\u003e\u003c/th\u003e\n \u003cth\u003e\n \u003cp\u003eCAD(n = 336)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth\u003e\n \u003cp\u003enon-CAD(n = 277)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAge (Male)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e57.67 ± 10.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e54.67 ± 9.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGender(years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e235(66.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e137(49.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSmoke[(n%)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e184(54.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e85(30.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eHT[(n%)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e223(66.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e119(43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eDM[(n%)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e115(34.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e46(16.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eBMI (kg/M\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e25.09(24.21,27.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e25.64(24.69,27.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.124\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e132.49 ± 19.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e130.51 ± 18.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.071\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eDBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e80.69 ± 13.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e79.46 ± 12.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.218\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eALT(U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e28.30(18.60,40.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e21.7(16.00,31.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAST(U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e24.7(19.20,35.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e21.55(17.90,26.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eScr(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e68.01 ± 15.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e64.30 ± 12.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTC (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.47 ± 1.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.49 ± 1.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.804\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTG (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.31 ± 1.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.83 ± 0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eHDL-C(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.08 ± 0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.19 ± 0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLDL-C(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.39 ± 0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.38 ± 0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.998\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eFPG (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5.86(5.03,7.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5.33(4.94,5.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eWBC (10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7.01(5.83,8.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6.02(5.15,7.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMON (10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.51 ± 0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.44 ± 0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLYM (10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.81(1.46,2.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.92(1.57,2.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.149\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNEU (10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.32(3.33,5.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.44(2.72,4.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.47(0.35,0.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.37(0.27,0.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.14(3.01,5.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.89(2.22,4.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNLR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.32(1.70,3.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.78(1.37,2.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e\u003cem\u003eValues are expressed as mean ± standard deviation, no. (%), or median (interquartile range). P \u0026lt; 0.05 (two-sided) was defined as statistically significant. Bold values indicate statistically significance.\u003c/em\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e\u003cem\u003eCAD: coronary artery disease; BMI body mass index, HT hypertension, DM diabetes mellitus, SBP systolic blood pressure, DBP diastolic\u003c/em\u003e blood pressure, \u003cem\u003eALT\u003c/em\u003e alanine aminotransferase, \u003cem\u003eAST\u003c/em\u003e aspartate aminotransferase, \u003cem\u003eCr\u003c/em\u003e creatinine, \u003cem\u003eTC\u003c/em\u003e total cholesterol, \u003cem\u003eTG\u003c/em\u003e triglycerides, \u003cem\u003eHDL-C\u003c/em\u003e high-density lipoprotein cholesterol, \u003cem\u003eLDL-C\u003c/em\u003e low-density lipoprotein cholesterol, \u003cem\u003eFPG\u003c/em\u003e fasting plasma glucose, WBC white blood cell, MON monocytes, LYM lymphocytes, NEU neutrophils, \u003cem\u003eMHR Monocyte-to-HDL-cholesterol ratio\u003c/em\u003e, NHR neutrophil-to- \u003cem\u003eHDL-cholesterol ratio, NLR neutrophil-to-lymphocyte ratio.\u003c/em\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003ch2\u003eLogistic regression analysis of MHR, NHR and NLR in CAD and non-CAD patients\u003c/h2\u003e\n\u003cp\u003eWe used univariate and multivariate logistic regression to analyze the association between CAD and different inflammatory markers (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). 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 \u0026lt; 0.001), NHR (OR = 1.36, 95% CI: 1.21–1.53, p \u0026lt; 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 \u0026lt; 0.001) were independently associated with CAD (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003ccaption language=\"En\"\u003eTable 2\u0026nbsp;\u003cp\u003eAssociation between MHR, NHR NLR, and CAD in logistic regression Models.\u003c/p\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth rowspan=\"2\"\u003e\u003cbr\u003e\u003c/th\u003e\n \u003cth colspan=\"2\"\u003e\n \u003cp\u003eModel 0\u003c/p\u003e\n \u003c/th\u003e\n \u003cth colspan=\"2\"\u003e\n \u003cp\u003eModel 1\u003c/p\u003e\n \u003c/th\u003e\n \u003cth colspan=\"2\"\u003e\n \u003cp\u003eModel 2\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth\u003e\n \u003cp\u003eOR (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth\u003e\n \u003cp\u003eOR (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth\u003e\n \u003cp\u003eOR (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTC (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.98(0.85–1.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.804\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTG (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.34(1.15–1.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.27(1.07–1.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.26(1.05–1.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eHDL-C(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.17(0.09–0.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.17(0.08–0.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.19(0.08–0.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLDL-C(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.00(0.80–1.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.998\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eWBC (10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.31(1.20–1.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.25(1.13–1.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.23(1.11–1.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMON (10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17.04(5.59–51.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.93(1.89–25.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.43(1.42–20.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNEU (10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.40(1.26–1.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.28(1.14–1.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.28(1.13–1.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21.56(8.35–55.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18.42(5.69–59.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15.57(4.68–51.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.47(1.33–1.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.36(1.22–1.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.36(1.21–1.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNLR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.54(1.33–1.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.24(1.07–1.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.28(1.09–1.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLogMHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.08(2.69–6.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.52(2.09–5.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.14(1.84–5.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003eModel 0, non-adjusted model.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003eModel I was adjusted for age, sex, ALT, AST, Scr and FPG.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003eModel II was adjusted for age, sex, smoking history, hypertension, diabetes mellitus.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003ch2\u003eROC curve analysis of MHR, NHR, NLR and CAD\u003c/h2\u003e\n\u003cp\u003eWe further evaluated the performance of MHR, NHR, and NLR in predicting CAD by ROC curves (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). 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.\u003c/p\u003e\n\u003ch2\u003eClinical and biochemical characteristics according to MHR tertiles\u003c/h2\u003e\n\u003cp\u003eThe study population was further divided according to MHR tertiles: Q1 (MHR ≤ 0.35, n = 204), Q2 (0.35 \u0026lt; MHR ≤ 0.51, n = 205), Q3 (MHR \u0026gt; 0.51, n = 204), as shown in the Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. 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 \u0026lt; 0.001) (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n\u003ctable border=\"1\" id=\"Tab3\"\u003e\n \u003ccaption language=\"En\"\u003eTable 3\u0026nbsp;\u003cp\u003eDemographic and clinical characteristics of participants by MHR\u003c/p\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth\u003e\u003cbr\u003e\u003c/th\u003e\n \u003cth\u003e\n \u003cp\u003eTertile 1\u003c/p\u003e\n \u003c/th\u003e\n \u003cth\u003e\n \u003cp\u003eTertile 2\u003c/p\u003e\n \u003c/th\u003e\n \u003cth\u003e\n \u003cp\u003eTertile 3\u003c/p\u003e\n \u003c/th\u003e\n \u003cth\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAge (Male)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e58.22 ± 9.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e57.11 ± 10.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e53.61 ± 11.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGender(years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e71(34.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e123(60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e178(87.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSmoke[(n%)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e40(19.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e87(42.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e142(69.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eHT[(n%)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e110(23.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e119(58.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e113(55.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.696\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eDM[(n%)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e46(22.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e53(25.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e62(30.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.195\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eBMI (kg/M\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e25.24(23.84–27.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e25.26(24.17–27.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e25.95(24.82–28.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e133.30 ± 17.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e131.39 ± 20.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e130.1 ± 19.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.236\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eDBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e79.58 ± 11.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e79.63 ± 13.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e81.19 ± 13.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.348\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eALT(U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e22.20(16.30–32.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e23.10(15.50-34.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e30.30(20.03–41.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAST(U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e22.20(18.40–28.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e21.25(17.40-27.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e25.20(20.60–34.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eScr(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e61.26 ± 12.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e65.08 ± 15.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e72.69 ± 13.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTC (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.65 ± 1.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.48 ± 1.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.23 ± 1.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTG (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.58(1.17–2.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.75(1.30–2.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.89(1.38–2.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eHDL-C(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.29 ± 0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.10 ± 0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.96 ± 0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLDL-C(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.46 ± 0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.39 ± 0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.32 ± 0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.152\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eFPG (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5.53(5.02–6.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5.54(4.98–6.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5.65(4.91–7.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.685\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eWBC (10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5.40(4.61–6.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6.62(5.68–7.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7.79(6.77–9.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMON (10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.34(0.28–0.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.47(0.41–0.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.61(0.53–0.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLYM (10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.70(1.42–2.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.94(1.50–2.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.00(1.61–2.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNEU (10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.96(2.51–4.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.87(3.10–4.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.86(3.82–6.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.38(1.87–3.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.52(2.74–4.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5.07(4.01–6.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNLR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.75(1.34–2.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.01(1.58–2.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.47(1.74–3.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCAD[(n%)]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e83(40.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e110(53.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e143(70.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e\u003cem\u003eValues are expressed as mean ± standard deviation, no. (%), or median (interquartile range). P \u0026lt; 0.05 (two-sided) was defined as statistically significant.\u003c/em\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003ch2\u003eAssociation between MHR and Gensini score.\u003c/h2\u003e\n\u003cp\u003eThe distribution of Gensini scores was examined according to grouping by MHR (Fig. \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e). 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 \u0026lt; 0.05) (Fig. \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e). Meanwhile, Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e 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 \u0026lt; 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 \u0026lt; 0.001) (Fig. 6).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u0026nbsp;\u003c/strong\u003eBinary and ordinal regression analysis on the risk of Gensini score of NAFLD patients according to MHR\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\"\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eGensini score = 0, non-CAD; 0 \u0026lt; Gensini score ≤ 25, mild coronary artery stenosis; 25 \u0026lt; Gensini score ≤ 50, moderate coronary artery stenosis; 50 \u0026lt; Gensini score ≤ 75, severe coronary artery stenosis; Gensini score \u0026gt; 75, very severe coronary artery stenosis. Adjusted: adjusted for gender, age, smoking.\u003c/em\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAs a novel and simple measure, MHR represents the balance of anti-inflammatory and pro-inflammatory. In the present study, we used coronary angiography to describe the presence of coronary stenosis and assessed the severity of CAD by the Gensini score. We demonstrated that MHR is an independent predictor of CAD in NAFLD patients despite adjusting for traditional CAD risk factors such as age, sex, smoking history, hypertension and diabetes. We also found that MHR was positively association with the severity of CAD in NAFLD patients. MHR, as a novel inflammatory biomarker, plays an important role in the emergence of CAD in NAFLD patients. Hence, MHR may prove to be a useful tool for predicting the existence and severity of CAD in NAFLD patients in clinical practice.\u003c/p\u003e \u003cp\u003eAs the central factor of inflammation, monocytes have been proved to play an important role in the progression of NAFLD [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Monocytes and the macrophages they give rise to are a significant source of various inflammatory factors in the liver, contributing significantly to the development of NAFLD [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Currently, it is believed that classical monocytes (CD14\u0026thinsp;+\u0026thinsp;+\u0026thinsp;CD16-) make up about 85% of all monocytes, non-classical monocytes (CD14\u0026thinsp;+\u0026thinsp;CD16++) make up 10%, and intermediate monocyte nuclear cells (CD14\u0026thinsp;+\u0026thinsp;+\u0026thinsp;CD16+) make up 5% of the total monocyte count. But intermediate monocytes are the most unstable, preferentially mobilized in an inflammatory environment and regulated the progression of liver fibrosis [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The data of Zhang et al. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] also demonstrated that an increase in the fraction of intermediate monocytes and a decrease in the fraction of classical monocytes were independently associated with NAFLD. These intermediate monocytes typically pass through CCL2, CCL5, and CXCL10 during inflammation recruited to the liver [\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. And differentiated into macrophages with dual pro-inflammatory and pro-fibrotic properties, which further contribute to liver fibrosis by activating hepatic stellate cells [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Second, monocytes also have a special role in atherosclerosis [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Upon activation, monocytes migrate into the subendothelium by adhering to the adhesion factors expressed by the damaged vascular endothelium [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. These macrophages are then transformed into foam cells by engulfing oxidized LDL-C, and they release pro-inflammatory and pro-oxidative cytokines that draw T lymphocytes and other monocytes to the site of inflammation [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe function of macrophages in the artery wall is only one aspect of monocytes' atherogenic impact. Many soluble factors associated with atherosclerosis could also activate circulating monocytes [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e], suggesting that circulating monocytes can participate in the development and progression of CAD by triggering inflammation. Additionally, tissue factor can be expressed by circulating monocytes in an inflammatory or prothrombotic condition, resulting in a procoagulant phenotype [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], which promotes the growth of atherosclerosis.\u003c/p\u003e \u003cp\u003eHigh-density lipoprotein (HDL-C), an anti-atherosclerotic factor, has been shown to have multiple biological activities, including reversal of cholesterol transport, anti-oxidative, anti-inflammatory, anti-apoptotic, anti-thrombotic and anti-atherosclerotic effects [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. It was demonstrated that HDL not only reduces monocyte recruitment to the arterial wall by decreasing the f-actin content of monocytes, but also reduces the expression of CD11b on monocyte and endothelial adhesion molecules and inhibits monocyte adhesion to the endothelium [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e], thus controlling the proliferation and activation of monocytes; achieving protection of endothelial cells from inflammation and oxidative stress [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Second, prior studies have noted that HDL-C, an anti-atherosclerotic lipoprotein, can inhibit monocyte tissue factor expression by preventing p38 activation and phosphoinositide 3-kinase inhibition [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Furthermore, HDL-C molecules have the ability to counteract macrophage migration and eliminate cholesterol in macrophages [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. In conclusion, HDL-C may inhibit the development of atherosclerosis through the inhibition of monocytes.\u003c/p\u003e \u003cp\u003eTherefore, inflammation may be a bridge factor for NAFLD patients with high CAD risk. And monocytes and HDL-C may have distinct functions in the progression or inhibition of arteriosclerosis in NAFLD patients. A model constructed using these two predictors, the emerging monocytes to HDL ratio (MHR) may be a better marker for assessing the development and progression of atherosclerosis in NAFLD patients. At present, a strong relationship between MHR and cardiovascular disease has been reported in the literature. Li et al [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e] proved that elevated MHR levels are associated with in-hospital MACE and long-term bleeding events in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients undergoing PCI. A meta-analysis of 11,345 CHD patients included 9 studies [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e] showed that high levels of MHR may be associated with higher long-term mortality and long-term MACE in CHD patients. In addition, MHR currently not only related to CVD. Huang et al [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] found that MHR was also an independent factor for NAFLD through a cross-sectional study, and a high MHR predicted a high risk of NAFLD. However, in reviewing the literature, no data was found on the association between MHR and CAD risk in NAFLD patients. Therefore, the present study was designed to determine the effect of MHR.\u003c/p\u003e \u003cp\u003eThis study also has several limitations. Firstly, this is a single-center retrospective study, including a small sample size, lack of follow-up data, and cannot prove the causal and prognostic relationship between MHR and CAD. Therefore, our findings need to be confirmed in other large prospective studies with long-term clinical follow-up. Secondly, the diagnosis of NAFLD is made by ultrasound examination. Ultrasound is not the most sensitive method for diagnosing fatty liver, and there are some false positives. However, due to the advantages of simplicity, convenience, and repeatability, ultrasound is still the most effective clinical diagnosis methods of NAFLD at present. Thirdly, due to the inability to accurately obtain a drinking history and to accurately define alcoholic fatty liver versus nonalcoholic fatty liver, we excluded patients with a previous drinking history when collecting participants, which may have resulted in a reduced sample size. Finally, because this study uses blood lipid indicators, patients who have previously received oral lipid-lowering medication were not excluded due to sample size issues, which could have affected some patients' LDL-C levels after taking the medication and resulted in different LDL-C levels between CAD patients and non-CAD patients. In conclusion, further studies are needed to investigate and validate the underlying mechanisms of the association between MHR levels and CVD in NAFLD patients.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe results of this study indicate that MHR in NAFLD patients with CAD was significantly higher than without CAD, and MHR was positively associated with the severity of CAD. MHR, as a simple and feasible inflammatory parameter, could be used to predict CAD risk in NAFLD patients in clinical practice. So, this indicator should be given more attention in the workup of NAFLD patients.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CAD: Coronary artery disease; CVD: Cardiovascular disease; DBP: Diastolic blood pressure; DM: Diabetes mellitus; FBG fasting blood glucose; HDL-C: High density lipoprotein cholesterol; HT: Hypertension; LDL-C: Low-density lipoprotein cholesterol; LYM: lymphocytes; MON: Monocyte; MHR: monocyte to high-density lipoprotein cholesterol ratio; NAFLD: Non-alcoholic fatty liver disease; NEU: neutrophils; Scr: Serum creatinine; NHR: neutrophil-to- HDL-cholesterol ratio; NLR: neutrophil-to-lymphocyte ratio; TC: Total cholesterol; TG: Triglyceride.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Medical Ethics Committee of Shanxi Medical University, which waived the need for written informed consent due to the retrospective study design.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eDate Availability\u003c/p\u003e\n\u003cp\u003eThe original contributions of this study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the National Natural Science Foundation of China (Grant No. 81970391), \u0026ldquo;Four a batch of\u0026rdquo; talent of Shanxi Province (2021RC08), and the Excellent Youth Foundation of Shanxi Province (Grant Number 201901D211504).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYZ and BL: study design; YZ and LW: data analysis; LP, LW, and JZ: manuscript drafting; YZ, LW, and JZ: data collection; LW, HF, and WZ: manuscript revision; BL: review and final approval. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe sincerely thank the arrhythmia team of the Second Hospital of Shanxi Medical University for supporting our work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePowell EE, Wong VW, Rinella M. Non-alcoholic fatty liver disease. The Lancet. 2021;397(10290):2212-24. \u003c/li\u003e\n\u003cli\u003eSatapathy S, Sanyal A. Epidemiology and natural history of nonalcoholic fatty liver disease. Semin Liver Dis. 2015;35(03):221-35.\u003c/li\u003e\n\u003cli\u003eMasarone M, Federico A, Abenavoli L, Loguercio C, Persico M. Non alcoholic fatty liver: epidemiology and natural history. Rev Recent Clin Trials. 2014 2014;9(3):126-33.\u003c/li\u003e\n\u003cli\u003eTargher G, Byrne CD, Tilg H. 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Medicine (Baltimore). 2022 2022 Aug 19;101(33): e30109.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Monocyte to high-density lipoprotein cholesterol ratio, Inflammation, Non-alcoholic fatty liver disease, Coronary artery disease","lastPublishedDoi":"10.21203/rs.3.rs-2198506/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2198506/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eNon-alcoholic fatty liver disease (NAFLD) is an independent risk factor for cardiovascular disease. Inflammation and dyslipidemia have been demonstrated to show excellent influence in atherosclerosis in patients with NAFLD. Monocyte (MON) and high-density lipoprotein cholesterol (HDL-C) ratio (MHR), one of the inflammation markers, is associated with the occurrence and severity of NAFLD. However, evidence of MHR in the risk of coronary artery disease (CAD) among NAFLD patients is limited.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective study of 612 patients with ultrasonogram-confirmed NAFLD who underwent percutaneous coronary intervention (PCI). All patients were divided into NAFLD\u0026thinsp;+\u0026thinsp;CAD group and NAFLD\u0026thinsp;+\u0026thinsp;non-CAD group. For univariate analysis between the two groups, continuous variables were compared using independent samples t-test or Mann-Whitney test, and categorical variables were compared using chi-square test or Fisher Exact tests. In addition, we used binary logistic regression analysis to identify risk and protective factors associated with CAD, constructed receiver operating characteristic (ROC) curves to assess the predictive value of MHR for CAD, and methodological studies of chi-square test for trend analysis the distribution of Gensini scores in MHR at different levels, and the risk degree of Gensini scores at different MHR levels by ordinal logistic regression.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe study included a total of 336 CAD patients and 277 non-CAD patients. Univariate analysis showed that CAD patients had higher MHR than non-CAD patients (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Meanwhile, compared with pure NAFLD patients, multivariate logistic regression analysis showed that MHR remained to be an independent risk factor for CAD after adjusting for confounding risk factors (OR\u0026thinsp;=\u0026thinsp;15.57, 95% CI 4.68\u0026ndash;51.85, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). At the same time, it was superior to traditional lipid parameters. NHR, NLR, and TG were also independent risk factors for CAD. HDL-C is a protective factor for CAD among NAFLD patients. The ROC curve showed that MHR or other inflammatory markers combined with traditional risk factors can improve the ability to predict CAD. In further study, trend chi-square showed that higher levels of MHR predicted more severe coronary lesions (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Multivariate ordinal logistic regression analysis showed that MHR was independently associated with changes in Gensini score (OR\u0026thinsp;=\u0026thinsp;2.95, 95% CI 1.78\u0026ndash;4.89, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe MHR was positively associated with CAD risk among NAFLD patients and reflected coronary atherosclerosis severity.\u003c/p\u003e","manuscriptTitle":"The monocyte to high-density lipoprotein cholesterol ratio is positively associated with the severity of coronary artery disease in patients with nonalcoholic fatty liver disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-11-01 19:23:44","doi":"10.21203/rs.3.rs-2198506/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d0153692-79d3-4964-b914-b21ddfde3e2b","owner":[],"postedDate":"November 1st, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-03-06T20:44:25+00:00","versionOfRecord":[],"versionCreatedAt":"2022-11-01 19:23:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2198506","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2198506","identity":"rs-2198506","version":["v1"]},"buildId":"-HB7Z8yhvgn0wM9Nzuekk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}