| Objective:Non-alcoholic fatty liver disease(NAFLD) is the most common cause of chronic liver disease in the world. NAFLD people are characterised by metabolic disorders, progression of atherosclerosis, and being likely to form thrombus, and atherosclerosis is one of the important potential factors effecting on the development of cardiovascular disease. Abnormal carotid artery intima-media thickness(IMTc) and formation of carotid atherosclerotic plaque are imageologic menifastations of carotid atherosclerosis which is an assessment of early-aged systemic atherosclerosis. As NAFLD is closely related to lipid abnormalities, non-high density lipoprotein cholesterol(non-HDL-C) seems to be better than low density lipoprotein cholesterol(LDL-C) to reflect changes of lipid metabolism in NAFLD patients. Oxidative stress may play an important role in the progression of atherosclerosis in NAFLD. This project aims to study relationship between NAFLD and non-HDL-C, relationship between non-HDL-C and atherosclerosis in NAFLD and its possible mechanisms.Methods:According to the Guide of diagnosis and treatment of Non-alcoholic Fatty Liver Disease in 2010 developed by Fatty Liver and Alcoholic Fatty Liver Study Group, Chinese Society Hepatology, Chinese Medical Association, 550 physical examinees with NAFLD were selected from Physical Examination Center in Hebei General Hospital from March to November while 500 age-matched physical examinees were selected for the control. Peripheral venous blood samples were collected from all physical examinees after they signed the informed consent form to centrifuged by 3000 revolutions per minute. The upper serum were stored at-80 until detection. ℃Serum lipid, glucose, liver and renal function biomarkers were detected by automatic biochemical instrument detection. The level of non-HDL-C was calculated by Frost method. Serum superoxides disambiguation of enzyme(SOD) and malondialdehyde(MDA) were measured. IMTc and carotid atherosclerotic plaque formation were examinated by ACUSONS2000 ultrasound. We used SPSS17.0 software for data analysis.Results:1050 patients, aged 40 and above with an average age of 52.93 ± 9.54 years were included in this study. All subjects were divided into two groups according to whether they have NAFLD or not. Five hundred patients with an average age of 52.63 ± 9.77 years were in NAFLD group, in which there were 369 men 131 women, and five hundred and fifty patients without NAFLD, in which there were 311 men and 239 women, with an average age of 53.27 ± 9.27 years served as the control group.1 General characteristics of NAFLD group and the control group: Results show that age and history of diabetes mellitus between two groups had no statistically significant difference(P=0.298, P=0.051). BMI(27.17 ± 2.70kg/m2 ± 2.79kg/m2 vs24.14), WC(96[90,101]cm vs 87[80,94]cm), SBP(131.06±16.74 mm Hg vs 123.92±16.65 mm Hg) and DBP(86[80,94]mm Hg vs80[80,88]mm Hg) of NAFLD patients are higher than patients without NAFLD with difference significantly(P for trend <0.001). NAFLD prevalence in male and female subjects are 54.2% and 32.8% respectively(P for trend <0.001).Compared to no-smoking subjects,more smokers with 59.4 percent suffer from NAFLD(P for trend <0.001). Analysis of lipid metabolism of two groups shows that in addition to high density lipoprotein cholesterol(HDL-C)(0.99[0.86,1.16]mmol/l vs 1.165 [1.00, 1.42]mmol/l) which is less than the control group, triglyceride(TG)(1.89[1.35,2.64]mmol/l vs 1.07[0.82,1.52]mmol/l), total cholesterol(TC)(5.11 ± 0.89mmol/l vs4.11 ± 0.88mmol/l) and low-density lipoprotein cholesterol(LDL-C)(2.92 ±0.747mmol/l vs 2.62 ± 0.694mmol/l) of NAFLD group are significantly higher(all P values for trend were below 0.001). We detected markers for evaluation of liver and renal function including aspartate amino transferase(AST)(20.00 [16.00,24.00] U/L vs 18.00 [15.75,21.00] U/L)(P for trend<0.001), alanine amino transaminase(ALT)(23.00[17.00,33.50]U/L vs 17.00[13.00,23.00]U/L)(P for trend<0.001), γ-glutamyl transferase(GGT)(33.00[23.00,49.00]U/L vs 16.00[3.61,25.00] U/L)(P for trend <0.001), as well as blood urea nitrogen(BUN)(5.08[4.38,6.01] mmol/lvs 4.97[4.03,5.88] mmol/l)(P=0.039), Creatinine(Cr)(86.00 [76.50, 94.00]umol/l vs 81.00[73.00,92.00]umol/l)(P for trend<0.001), Uric acid(Uric)(353.00 [304.50,406.50]umol/l vs 291.00 [248.50, 348.50]umol/l)(P for trend<0.001), all of which are higher in NAFLD group than those in the control group with significant difference. Serum SOD levels were higher in NAFLD group(11.97±4.76U/ml vs 13.33±4.72U/ml)(P for trend<0.001) than those in the control group while MDA levels are lower(5.67±1.34nmol/ml vs 5.30±1.96nmol/ml)(P=0.001). Chi-square test shows that incidence of carotid atherosclerosis in both groups are 51.0% and 37.7% respectively(χ2=16.581, P<0.001).2 Correlation between NAFLD and Non-HDL-C: We find significant difference between two groups(3.96±0.84mmol/l vs 3.46±0.89mmol/l). Non-HDL-C levels were then divided into four groups according to the quartiles. It can be seen that NAFLD prevalence increases with increasing non-HDL-C levels, 26.8%,44.0%,54.1%,66.2%(P for trend<0.001) respectively in different groups. Each two groups were compared respectively and all P values for trend were below 0.001 which should be compared to a’(=0.0167). Gender, BMI, WC,GGT,Uric,FBG,non-HDL-C and HDL-C in both group, history of smoking and hypertension in both groups were analyzed by binary logistic regression analysis and the result showed that the OR values were 1.874(95%CI:1.071-3.280), 1.666(95%CI: 1.239-2.240), 1.053(95%CI:1.017-1.091), 1.022(95%CI:1.013-1.032), 1.005(95%CI:1.002- 1.008), 1.218(95%CI:1.036-1.433), 1.285(95%CI:1.039-1.589), 0.194(95%CI: 0.104-0.360), 1.087(95%CI:0.741-1.593) and 1.070(95%CI: 0.699- 1.637). Apart from smoking history and hypertension, all of the other index had statistical significance(P for trend<0.05). Reflected from the results, HDL-C is a protective factor for NAFLD, while male, BMI, WC, GGT,Uric,FBG,and non-HDL-C are independent risks for NAFLD.3 Relationship between NAFLD and LDL-C: LDL-C levels in NAFLD group were significantly higher than those in the control group(2.92±0.747mmol/l vs 2.62±0.694mmol/l)(P < 0.001).BMI, WC, fasting blood glucose, non-HDL-C, LDL-C, TC, TG of all subjects in the logistic regression show that OR values are respectively 1.845(95%CI: 1.425-2.387),1.046(95%CI:1.018-1.074), 1.270(95%CI:1.090-1.479), 2.553(95%CI: 1.355-4.81),1.657(95%CI: 1.034-2.655),0.369(95%CI: 0.216-0.630),1.602(95%CI:1.286-1.997), and P values are 0.000, 0.001, 0.002, 0.004, 0.036, 0.000,0.000, respectively. We find that the correlation between non-HDL-C and NAFLD is stronger than that of LDL-C and triglycerides.4 Relationship between incidence of carotid atherosclerosis and nonHDL-C in patients with NAFLD: NAFLD subjects were divided into four groups by four percentiles of non-HDL-C levels, and the incidence of carotid atherosclerosis are 39.90%,47.20%,56.60%,60.20%(P for trend 0.009), respectively. As the baseline, the average in Q1 group is the lowest compared respectively to Q2,Q3 and Q4. P values were 0.234, 0.011 and 0.002, respectively. The P-values were compared to a’ =0.017. We found statistical significance in the comparison between Q3, Q4 and Q1. We find that incidence of carotid atherosclerosis increases with the increasing levels of non-HDL-C.5 Correlation between non-HDL-C and SOD in patients with NAFLD: NAFLD subjects were divided into four groups by four percentiles of non-HDL-C levels. Averages of SOD respectively are 14.78 ± 5.02nmol/ml, 12.19± 3.07nmol/ml, 11.65 ± 5.04nmol/ml and 9.46 ± 3.98nmol/ml. Each two groups were compared respectively and all P values for trend were below 0.001.We find that SOD levels decreases with the increasing levels of non-HDL-C.6 Correlation between non-HDL-C and MDA in patients with NAFLD: NAFLD subjects were divided into four groups by four percentiles of non-HDL-C levels. Averages of MDA respectively are 4.86±1.40nmol/ml,5.42±1.05nmol/ml, 5.75±1.05 nmol/ml and 6.53±1.22nmol/ml. Each two groups were compared respectively. The difference is significant(P=0.001, P<0.001, P<0.001).We find that MDA levels increases with the increasing levels of non-HDL-C.7 Relationship between Non-HDL-C and SOD, MDA in the control group:Subjects without NAFLD were divided into four groups by four percentiles of non-HDL-C levels. No matter SOD or MDA, no significant trend and statistical difference were found when they were compared respectively in four groups(P for trend >0.05).Conclusion:The levels of non-HDL-C were higher in NAFLD people. Non-HDL-C was associated with oxidative stress in patients with NAFLD. Oxidative stress may be involved in promoting atherosclerosis and cardiovascular disease with increased level of non-HDL-C. |
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