Metabolic syndrome in systemic lupus erythematosus was closely related to body mass index, blood pressure, blood sugar, blood lipids, and arthritis

Background and Objective: Prevention and control of metabolic syndrome is the key to improving the development of systemic lupus erythematosus. The aim of this study was to analyze the relevant factors regarding metabolic syndrome (MS) in systemic lupus erythematosus (SLE). Methods: A total number of 1238 SLE patients in Yijishan Hospital of Wannan Medical College, Anhui province, from February 2012 to July 2017, were analyzed retrospectively. SLE patients with MS were grouped to group SLE-MS, the others without MS was grouped to group SLE-nMS. The two groups were compared with respect to general characteristics, clinical signs, and laboratory parameters. Random forest approach and multivariate logistic regression were conducted to analyze the related factors regarding MS in SLE. Results: The constituent ratio of metabolic syndrome was 27.14% (336/1238). More SLE patients with MS presented with more farmers, more married people, lower education level, and more lupus nephritis, proteinuria, oral ulcers, tubular urine, hematuria than SLE patients without MS (P<0.05). Moreover, eighteen important variables, whose average importance scores were highest and whose error rates were lowest, were selected by random forest method. Data from multivariate logistic regression showed that MS in SLE was related with BMI, diastolic blood pressure, systolic blood pressure, fasting blood glucose, arthritis, urea, triglycerides, high-density lipoprotein, and white blood cells. Conclusion: MS in SLE was closely related to BMI, blood pressure, blood sugar, blood lipids, arthritis, white blood cells, and urea. Targeted prevention and conclusion measures for the risk factors should be taken as early as possible.


INTRODUCTION
Systemic lupus erythematosus (SLE) is an autoimmune-mediated diffuse connective tissue disease characterized by immune inflammation. The incidence of SLE in the world is about (7.4~159.4)/100,000, which seriously endangers the physical and mental health of residents and becomes an important global public health problem. 1 The majority of SLE patients were women, and the incidence of myocardial infarction, congestive heart failure, and stroke in SLE women increased by 8.5 times, 13.2 times, and 10.1 times, respectively, and SLE patients developed menopause 3-4 years earlier than ordinary women. 2 The incidence of hypertension, diabetes, elevated very low-density lipoprotein, elevated triglycerides and atherosclerosis in SLE patients is significantly higher than that in the general population, and the absolute risk of coronary heart disease in SLE exceeds that in Type-2 diabetes. [3][4][5] These studies have shown that the risk of cardiovascular disease (CVD) in SLE patients is significantly higher than in the general population.
The late cause of death in patients with SLE is primarily CVD. The increase in CVD risk in SLE is caused by multiple factors. Selzer et al. selected 214 women with SLE who had no clinical manifestations of cardiovascular disease and found that carotid plaque formation and hypertension were associated with a decrease in high-density lipoprotein. 6 Hyperlipidemia and hyperglycemia are independent risk factors for intimal thickening, and hardening of the aorta is also associated with hypertension. Studies have found that serum total cholesterol (TC) greater than 5.2mmol / L can predict the occurrence of coronary heart disease (CHD) in SLE patients, 24% of patients with elevated TC levels have CHD, and only 3% of patients with normal TC levels developed CHD. 7 The role of these traditional risk factors in the development of atherosclerosis in SLE patients cannot be ignored, and metabolic syndrome (MS) is just a collection of risk factors, that is, central obesity and insulin resistance as the central link, with hypertension, a group of metabolic disorders with hypertriglyceridemia, impaired glucose tolerance, or type 2 diabetes as the main clinical manifestations. 8 MS is an independent risk factor for CVD in patients with SLE. So prevention and control of MS is the key to improving the development of SLE. 9,10 This study analyzed the data of 1238 patients with SLE in order to explore the relevant factors of MS in SLE patients. General characteristics, clinical signs, and laboratory parameters were obtained through epidemiological interviews and hospital records. Patients were randomly selected from ligible cases in the ward of the hospital's Rheumatology Department based on their hospitalization number and a random number table. Statistical analysis: Epidata 3.0 software was used to enter data, and SPSS 17.0 software was used for single factor analysis and multivariate analysis. The R 3.5.1 software RandomForest command package is used for dimensionality reduction and initial screening of variables. We use the random forest algorithm to sort the importance of variables, run the sliding window sequential forward feature selection (SWSFS) process, 14 plot the error rate graph, and combine the variables with the lowest error rate into the binary logistic regression model. Numerical data conforming to normal distributions were presented as means± standard deviation (SD); those not normally distributed were presented as medians (interquartile range, IQR). Mann-Whitney rank sum tests or Two-tailed Student's t-tests for independent samples were performed to estimate differences between groups for continuous variables. The Chi-squared test and Fisher's exact test were used to assess differences in categorical variables among groups. A two-tailed p value <0.05 was taken to be statistically significant.

Ethics approval and consent to participate:
The study was approved by the Ethics Board of Wannan Medical College (Number: 2016032; date: December 15, 2015). All patients gave informed consent for publication in the research study and patient privacy was protected.

RESULTS
Participants with MS accounted for 27.14% of SLE patients. The age (P=0.145) and gender (P=0.662) between the SLE-MS group and the SLE-nMS group were not statistically different. The proportion of farmers, married people and low education level in the SLE-MS group was statistically higher than that in the SLE-nMS group (P<0.05) ( Table-I).
The proportion of participants with lupus nephritis (LN), proteinuria, mouth ulcers, Cylindruria and hematuria in the SLE-MS group was statistically higher than that in the SLE-nMS group (all P<0.05) ( Table-II).

Metabolic syndrome in systemic lupus erythematosus
We performed binary logistic regression analysis with or without MS as the dependent variable and the top 18 indicators of variable importance score as independent variables. The results showed that BMI, DBP, SBP, GLU, arthritis, UA, TG, and HDL were associated with MS in SLE (Table-V).

DISCUSSIONS
The clinical manifestations of almost all autoimmune diseases are likely to occur in SLE. Therefore, most scholars call it the prototype of autoimmune diseases, and its pathogenesis is still unclear. 15 MS is related to the occurrence of CVD in SLE patients. Preventing the occurrence of MS in SLE patients is beneficial to the control of their condition. This study showed that the prevalence Lai-Run Jin et al. This study showed that MS in SLE patients is associated with farmers, married, and low levels of education. This may be because farmers have   19 Therefore, the prevention and treatment of MS in SLE patients should focus on farmers and low-education populations, and their health knowledge promotion and health services should be strengthened. Lupus nephritis (LN) is a serious and common complication of SLE, which can significantly increase the incidence and mortality of SLE. 20 This study found that the occurrence of MS in SLE patients is related to LN, which is consistent with the results of Zhang M et al. 21 LN patients have a variety of autoimmune lymphocytes and autoantibodies, which can activate endothelial cells and cause CVD. Therefore, LN itself is a risk factor for CVD in SLE patients. The risk factors of LN include family history, smoking history, age, etc. At the same time, the components of blood glucose, blood pressure, blood lipids and body weight in MS interact with each other in metabolism, which is also an important risk factor for LN. Moreover, the proportion of arthritis, proteinuria, mouth ulcer, tubular urine and hematuria in SLE-MS patients was significantly different from that in SLE-nMS group (P<0.05), suggesting that symptomatic treatment of these signs in clinical practice is of great significance for the prevention and control of MS in SLE.
Red blood cell distribution width (RDW) is a parameter that directly describes red blood cell heterogeneity and is generally used to differentially diagnose thalassemia, giant cell anemia, and iron deficiency anemia. Recently, RDW has been found to be a strong independent predictor of allcause mortality in coronary atherosclerotic heart disease (CAD), acute coronary syndrome (ACS), hypertension, and diabetic nephropathy. 22,23 Univariate analysis of this study showed that RDW was associated with SLE-MS, similar to our previous survey of metabolic syndrome in community physical examination populations, suggesting that RDW, a simple, inexpensive and readily available parameter, has good early warning and prognostic evaluation values in SLE-MS. 18 The univariate analysis of this study showed that SLEDAI was associated with MS in SLE, indicating that MS may affect the severity of SLE disease.
Multivariate logistic regression analysis of this study showed that BMI, SBP, DBP, GLU, TG, and HDL were related to MS in SLE. These reflect the relationship between obesity, hypertension, hyperglycemia, dyslipidemia and MS in the general population also exists in SLE patients. 24,25 Multivariate analysis showed that arthritis was a risk factor for MS in SLE. Lee et al. found that the prevalence of MS in healthy controls was significantly lower than in patients with rheumatoid arthritis and the results support the views of this paper. 26

Limitations of study:
Several limitations exist in the current study. The lifestyle and dietary habits of the subjects in this study were not analyzed, so they need to be improved in future work.
The patients with SLE in this study were recruited from only one hospital and the promotion of conclusions needs to consider regional factors. In addition, distorted results in epidemiological association studies can be resulted in by potential biases in case-control studies. Consequently, further studies are needed to clarify the exact influencing factors on MS in SLE.

CONCLUSION
The occurrence of MS in SLE patients is closely related to BMI, blood pressure, blood sugar, blood lipids, and arthritis.