Metabolic Syndrome Among Patients with Rheumatoid Arthritis and the Correlation with Disease Activity

CRISTINA GABRIELA ENE1#, MIHAELA MITROI2*, IONELA MIHAELA VLADU3#, LUCRETIU RADU4, TIBERIU STEFANITA TENEA COJAN5, ANCA MIHAELA PREDESCU6, MARIUS GABRIEL BUNESCU7 1University of Medicine and Pharmacy of Craiova, Pharmacology Department, Emergency Clinical Hospital of Craiova, 2-4 Petru Rares Str.,200349, Craiova, Romania 2University of Medicine and Pharmacy, Craiova Department of Otorhinolayngology, County Hospital Craiova, 2-4 Petru Rares Str., 200349,Craiova, Romania 3University of Medicine and Pharmacy of Craiova, Department of Metabolism and Nutrition Diseases, Filantropia Clinical Hospital of Craiova, 1 Filantropiei Str., 200143, Craiova, Romania 4University of Medicine and Pharmacy of Craiova, Department of Hygiene, Filantropia Clinical Hospital of Craiova, 1 Filantropiei str., 200143, Craiova, Romania 5University of Medicine and Pharmacy of Craiova, Department of Surgery, CFR Hospital of Craiova, Stirbei-Voda Str., 200374,Craiova, Romania 6University of Medicine and Pharmacy of Craiova, Faculty of Dentistry Medicine, Histology Department, 2-4 Petru Rares Str., 200349, Craiova, Romania 7University of Medicine and Pharmacy of Craiova, Occupational Medicine Department, 2-4 Petru Rares Str., 200349, Craiova, Romania

Rheumatoid arthritis (RA) is an autoimmune condition characterized by a systemic aberrant inflammatory response whose main feature is joint damage especially to the small joints of the hands and feet.
The character of systemic disease is demonstrated by multiple extraarticular affections and numerous studies have demonstrated that approximately between 50% and 80% of RA patients present extraarticular manifestations during the course of the disease and their presence is associated with a more aggressive disease status.
Patients with RA have a higher risk of cardio-vascular mortality that in general population. There are numerous studies sugesting that inflamation plays a key role in the develompent of atherosclerosis and heart disease, therefore a better understanding of the inflamatory response in RA may lead to better outcomes for patients with RA.
Metabolic syndrome is a group of major risk factors for type 2 diabetes and cardiovascular diseases (CVD), including insulin resistance, abdominal obesity, dyslipidemia, hypertension, and impaired fasting glucose, incorporated into a single disease group [4].

Experimental part
Aim of the study The present study aims to evaluate the prevalence of MetS and it's components in patients with RA. Correlation between disease activity, inflamation response in RA and the presence of MetS among patients with RA could identify subjects at an aditional higher risk of cardio-vascular events in order to provide a better outcome in management of patients with RA.

Material and methods
The conducted study was a prospective longitudinal study and included 120 patients previously diagnosed with RA undergoing different type of Disease-modifying antirheumatic drugs (DMARDs) in the Medical Clinic of the Railway Clinical Hospital of Craiova from January 2017 to January 2019 and a control group consisting of 120 patients comparable to age and sex without RA that were hospitalized in the same clinical service.
For all the patients included in the study, RA diagnosis was according to the 2010 American College of   [5].
The assessment of MetS was made for all the patients included in the study. MetS was defined according to International Diabetic Federation -National Cholesterol Education Programme Adult Treatment Panel III (IDF -NCEP ATP III) guidelines where a minimum of 3 criteria must be fulfilled for the diagnosis of Metabolic Syndrome (table 1).
For all the patients included in this study, demographic data regarding sex and age were collected, blood preasure (systolic and diastolic) was measured each, day during their hospitalisation and anthropometric measurements were taken (weight, height, waist circumference). Blood samples were collected from which we tested total cholesterol, high density lipoprotein cholesterol (HDL-C), triglycerides, serum glucose concentration.
Additionally, for the patients with RA, the erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), Creactive protein (CRP), and anticyclic citrullinated peptide (anti-CCP) were measured and the assessment of disease activity was made using the Disease activity score of 28 joints (DAS28-ESR) (table 2).
The study was conducted according to the Declaration of Helsinki and local regulations. Ethical approval for the study was obtained from the local ethics commitee and also, patients in both groups signed an informed consent.
Statiscal analysis were made using IBM Statistical Package for Social Science (IBM SPSS) V 20.0 where a p value < 0.05 was considered significant.

Results and discusions
The analisys of the demographic data showed no statistically significant differences between the studied groups. Among the RA patients 89 (74.16%) were women and 31 (25.83%) were men, while in the control group 85 were women (70.83%) and 35 (29.16%) were men ( fig.  1). Patients in RA group were aged between 26 and 72 years old with a mean age of 52.77 ± 10.40, while in the control group, patients were aged between 23 and 75 years old with a mean age of 53.55 ± 11.49 (p=0.585) (table 3).
Regarding the prevalence of MetS in both groups, we found that this was higher in the RA group comparing to the control group (p=0.005)( fig. 2)     Disease activity was also evaluated in patients with RA. Our study showed that DAS28-ESR was significantly higher in RA patients with MetS (3.70± 0.644) than in RA patients without MetS (3.35 ± 0.725) (table 6).
The cardiovascular risk quantitation is a golden desideratum for clinical management [6][7][8] allowing a better and more accurate medical care for the patients.
Patients with RA are known to have an increased risk of cardiovascular events early in life [9] than in general populations. Meune C et al on a meta-analysis over 50 years showed that RA is associated with a increased morbidity and mortality by up to 50% compared with general population [10].
Atherosclerosis in considered to be responsable for CVD but traditional risk factors for CVD do not entirely explain the increased risk of CVD in patients with RA. [11] The inflamatory response in RA is known to act on adipose tissue and the endangium resulting in a increased insulin resistance and destruction of endangium. Due to chronic pain percieved by patients with RA, low levels of physical activity are common in this patients resulting in increased adipose tissue. Obesity is known as one of the most important risk factor for cardiovascular disease. [12][13][14][15] The prevalence of obesity has increased by 10-40% over the past ten years with an estimated number of 302.1 million adult with obesity worldwide (8.2% of the world's population) [16]. Many studies sugest that adipose tissue represents a source of proinflamatory cytokines -like interleukin 6 (IL-6) or tumour necrosis factor α (TNF α).

Conclusions
The presented study showed a significant higher prevalence of metabolic syndrome in patients with rheumatoid arthritis coparable with control group.
Comparing the prevalence of metabolic syndrome components in both group, we observed that each component of metabolic syndrome had a significantly higher prevalence among patients with rheumatoid arthritis comparable to control group.
A correlation between disease activity of rheumatoid arthritis and metabolic syndrome showed that patients with both rheumatoid arthritis and metabolic syndrome had higher values of DAS28-ESR index comparable with patients with rheumatoid arthritis without metabolic syndrome.