Comparing the prevalence of metabolic syndrome in systemic lupus erythematosus , rheumatoid arthritis and psoriatic arthritis : A cross sectional study

Maryam Mobini*, Fatemeh Niksolat, Reza Ali Mohammadpour, Sara Sadr, Saeed Dashti dargahloo Department of Internal Medicine, Diabetes Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Department of Internal Medicine, Orthopedic Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Department of Biostatistics, Diabetes Research Center, Faculty of Health, Mazandaran University of Medical Sciences, Sari, Iran; Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran


Introduction ____________________________
Coronary artery disease is a leading cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and psoriatic arthritis (PsA).It has been reported that female SLE patients have a 5-6-fold higher risk of developing cardiovascular disorders (CVD), and the risk for women with SLE aged 35-44 years is increased more than 50 fold [1].CVD was more prevalent in RA (10.5%) than in PsA (7.2%) (2).RA patients have a 2-3 fold higher risk of myocardial infarction and up to 50% higher risk of CVD mortality [2].
Metabolic syndrome (MetS) includes a group of classic CVD risk factors such as central obesity, hypertension, hypertriglyceridemia (TG), and low highdensity lipoprotein cholesterol (HDL-c) [3].Moreover, MetS is related to the inflammatory response and pro inflammatory cytokines such as IL-6 and TNF-α that facilitate insulin resistance.Patients with MetS are reported to present high levels of C-related protein (CRP), interleukin-1β (IL-1β), IL-1, P-selectin, intercellular adhesion molecule, and leptin [4,5].Various medications such as anti-inflammatory and immunosuppressive drugs may play a role in MetS and CVD [6].The prevalence rates of MetS in SLE, RA, and PsA patients were found in different studies to be 16.3%-45.2%,13.9%-51.3%,and 25.5%-44%, respectively [7][8][9][10][11][12].Some studies have shown that MetS and its components are more prevalent in PsA than in RA [7,13,14], but their prevalence rates are the same in SLE and RA [15].SLE, RA, and PsA are three prevalent and indicator disorders in rheumatology.The evaluation of comorbidities may play a role in prioritizing and selecting appropriate treatments and management.The present study evaluated and compared the prevalence of MetS in these three disorders.Focus was also placed on some characteristics of these disorders in regard to MetS and the factors that might relate to them.Five patients with SLE, 3 patients with PsA, and 12 patients with RA were excluded from the study, because they were found to be outside the age range.Sequential sampling was performed to find a statistically significant difference between at least two groups.The minimum sample size was calculated as 45 in PsA with a higher MetS prevalence rate, a 95% confidence level, and a power of 80%.In order to reduce potential bias, the researchers attempted to recruit participants from a certain age range and from both private and public services.

Assessments and data collection
Patients in each groups were evaluated clinically based on disease: Systemic Lupus Disease Activity Index (SLEDAI), Systemic Lupus Damage Index (SDI), and Health Assessment Questionnaire (HAQ) for SLE; Disease Activity Index 28 (DAS) and HAQ for RA and PSA.
All participants were clinically and biochemically assessed to define their metabolic profiles: type 2 diabetes with or without treatment, arterial blood pressure, lipid profile (HDL-c and TG), fasting blood glucose, and waist circumference.
MetS was assessed and recorded consecutively by rheumatologists according to the National Cholesterol Educational Program Adult Treatment Panel III (NCEP ATP III) and IDF [3,19].MetS was considered to be present based on the NCEP criteria if patients met three or more of the following conditions: 1. Waist circumference ≥102 cm for men and ≥88 cm for women 2. Patient is currently using an antihypertensive agent, has a systolic blood pressure ≥130 mmHg, or a diastolic blood pressure ≥85 mmHg 3. Level of HDL cholesterol <40 mg/dl for men and <50 mg/dl for women 4. Level of TGs ≥150 mg/dl 5. Fasting blood glucose level ≥110 mg/dl.
The IDF criteria included a waist circumference ≥94 cm for men and ≥80 cm for women in addition to other defining criteria of MetS.Furthermore, the variables age, gender, and treatment modalities (current therapies including HCQ, prednisolone, and methotrexate) were also considered.The cumulative dose of prednisolone was calculated based on the duration of treatment and cumulative dosage (grams) of prednisone or equivalent medication at enrollment in the study as well as the application of glucocorticoid pulse therapy.
Each patient's waist circumference was measured at the end of a normal expiration, in a horizontal line at the level of the iliac crest, parallel to the floor.Blood pressure (BP) was measured twice at rest, and the lowest measure was used for systolic and diastolic blood pressure.
Blood was drawn from patients after an overnight fasting period, and glucose and lipid profiles [total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol (LDL-c), and TGs] were measured enzymatically.

Statistical analysis
Demographic and clinical features and prevalence of MetS and its components in patients and controls were evaluated.The age-adjusted prevalence rate was calculated by direct methods.Statistical analysis was performed using ANOVA to compare the quantitative variables, and chi-square tests were used to compare qualitative variables among the 4 groups using SPSS version 19 (Chicago, USA).Results were considered significant at p<0.05.

Discussion ______________________________
This is a cross-sectional study of the prevalence of MetS in patients with SLE, PsA, and RA compared with controls.In the current study, MetS occurred more frequently in patients with PsA and SLE than in those with RA and the controls.PsA patients showed the highest prevalence of hypertension.
The population prevalence of MetS, based on NCEP/ATP III criteria, was 29% in an Iranian population (35% in females vs. 24% in males) in the period 2005-2016 [20].In the present study, the prevalence of MetS in the controls was 34.9%, which was slightly higher than expected.The majority of patients in all groups were female, especially the SLE patients, and based on the epidemiology of these diseases, it was expected.
The causes of the variance in the prevalence of MetS in patients with rheumatic diseases are not totally clear.Contrary to Gomes et al. [10], who reported a significant increase in the prevalence of MetS in 338 patients with RA compared to 84 controls, an increased prevalence of MetS could not be demonstrated in the 140 RA patients of the current study.This is consistent with the results of Karvounaris et al.The relationship between the prevalence of MetS and inflammatory rheumatoid diseases seems to be complex and to depend on several factors.Inflammatory cytokines such as TNFα and interleukin 6 (Il-6) were found to reduce insulin activity, inhibit insulin receptor auto phosphorylation, and signal transduction that leads to hyperglycemia, compensatory hyperinsulinemia, and dyslipidemia [22,23].On the other hand, abdominal fat may be a source of the production of cytokines such as TNFα, IL-6, and adiponectin [24].Chronic treatment with various medications such as glucocorticoids and hydroxychloroquine, physical activity, and concomitant disorders such as hypothyroidism may contribute to changes in the incidence of hypertension, blood glucose, lipid profile, and visceral obesity.In the present study, SLE patients used more steroids and hydroxychloroquine (at higher doses), while methotrexate was more common in PsA patients (Table 2).The lower LDL values in SLE patients may be due to the greater use of statins and hydroxychloroquine for this condition.Lower levels of blood sugar in RA patients could be associated with hydroxychloroquine intake.Although the use of steroids was less common in psoriasis, the odds of MetS were higher.HAQ and DAS 28 were higher in PsA patients, which may indicate a greater incapacity in these patients and, as a result, a decrease in their daily physical activity.Hypothyroidism was more prevalent in PsA patients (42.2%) and lower in those with RA (9.3%; p=0.000).
According to previous studies, MetS is more prevalent in patients with PsA than in those with RA, while it is seen in the same pattern in SLE and RA patients (Table 4) [7,14,15].
In the current study, MetS occurred in one-third to one-half of the patients.This is in accordance with some other studies, although a direct comparison is difficult because of differences in patient selection and some parameters such as age, disease duration and manifestations, and different modalities of immunosuppressive therapies.Considering the high prevalence of MetS in the patients of this study, routine screening for MetS components is recommended, especially in PsA and SLE patients.
[21], who found a similar prevalence of MetS in 200 RA patients and 400 control subjects, and the findings of Mok et al. [7] with 699 RA patients and 1398 controls.The current results in comparing the rate of MetS in PsA and RA patients were consistent with those of Labitigan et al. [13] and Mok et al. [7] but inconsistent with the results of Zonana-Nacach et al. [15] in SLE and RA patients.To the best of the authors' knowledge, no study has compared the prevalence rates of MetS in these three diseases.

Table 1 .
Demographic data, clinical and laboratory characteristics in SLE, PsA, RA patients and controls SLE: systemic lupus erythematosus, PsA: psoriatic arthritis, RA: rheumatoid arthritis.* Derived from one-way analysis of variance (continuous variables) or Chi-Square test (categorical variables).** Post hoc multiple comparison of continuous variables was performed by Tukey's test.

Table 2 .
Clinical and laboratory characteristics in SLE, PsA, and RA patients SLE: systemic lupus erythematosus, PsA: psoriatic arthritis, RA: rheumatoid arthritis.* Derived from one-way analysis of variance (continuous variables) or Chi-Square test (categorical variables).** Post hoc multiple comparison of continuous variables was performed by Tukey's test.

Table 3 .
Metabolic syndrome and its components in SLE, PsA, RA patients, and controls *Derived from Chi-Square Tests (categorical variables).

Table 4 .
Studies on the prevalence of metabolic syndrome in patients with rheumatologic disorders