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ORIGINAL ARTICLE
Ahead of print publication  

Prevalence of metabolic syndrome in rheumatoid arthritis patients: Association with disease


1 Department of Rheumatology, Charles Nicolle Hospital; Tunis El Manar University, Tunis, Tunisia
2 Tunis El Manar University; Department of Cardiology, Charles Nicolle Hospital, Tunis, Tunisia
3 Tunis El Manar University; Department of Biochemistry in Charles Nicolle Hospital, Tunis, Tunisia
4 Department of Rheumatology, Charles Nicolle Hospital; Tunis El Manar University, Tunis, Tunisia, Tunis

Date of Submission16-May-2021
Date of Acceptance01-Oct-2021
Date of Web Publication26-Jul-2022

Correspondence Address:
Leila Rouached,
Department of Rheumatology, Charles Nicolle Hospital, Tunis
Tunisia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_122_21

  Abstract 


Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease, which is associated with an increased risk of cardiovascular disease (CVD). Metabolic syndrome (MetS) is a set of factors that increase the risk of CVD, and recent studies suggested an increased prevalence of MetS in RA more than in general population.
Aim: The aim of this study is to determine the prevalence of MetS in patients with RA and to evaluate its association with the disease activity and inflammation parameters. Then, to evaluate other cardiovascular risk factor and HeartSCORE Eular 2015 and its relation with the MetS.
Methods: It is a cross-sectional study of 103 RA patients assessing the prevalence of the MetS in RA patients. MetS was defined according to the National Cholesterol Education Program/Adult Treatment Panel III guidelines. RA disease activity was assessed with CDAI, SDAI and DAS28 scores. Independent risk factors for MetS in RA patients were identified by logistic regression.
Results: The mean age was 53 ± 10 years. The sex ratio (Male/female) was 0.3. About half of patients (45%) had moderate disease activity with a mean DAS28 CRP score of 3.9±1.38. Prevalence of MetS was 38.8% in RA patients. MetS was associated with higher age (P=0.03), late onset disease age (P=0.01), family history of CVD (P=0.016), current use of corticoid (P=0.01) and menopause status (P=0.006). However disease activity, inflammation or treatment were not associated with MetS.
Conclusions: MetS in RA patients was not associated with inflammation and disease activity.

Keywords: Disease activity, metabolic syndrome, rheumatoid arthritis



How to cite this URL:
Tekaya R, Rouached L, Ahmed HB, Tekaya AB, Bouzid K, Bouden S, Saidane O, Mahmoud I, Abdelmoula L. Prevalence of metabolic syndrome in rheumatoid arthritis patients: Association with disease. Indian J Rheumatol [Epub ahead of print] [cited 2022 Dec 5]. Available from: https://www.indianjrheumatol.com/preprintarticle.asp?id=352103




  Introduction Top


Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease, which causes articular and extra-articular manifestations. It is associated with an increased risk of cardiovascular disease (CVD) and is considered an independent risk factor for this outcome.[1] Traditional risk factors, such as age, smoking, abdominal obesity, history of CVD in family history, diabetes, and hypercholesterolemia, cannot explain this increased risk of CVD in RA. The inflammation plays also a role in accelerating atherosclerosis in RA patients. Recent studies demonstrated that with a tightly controlled treatment of RA, the increased mortality associated to RA could be prevented.[2] Metabolic syndrome (MetS) is a set of factors that increased the risk of CVD, and it consists of abdominal obesity, insulin resistance, hypertension, reduced levels of high-density lipoprotein cholesterol (HDL-c), and high levels of triglycerides.[3] Recent studies have suggested an increased prevalence of MetS in rheumatic diseases (14%–62.8%) more than in general population,[4] especially in RA, and associations between MetS and specific disease parameters.[5],[6]

The aim of this study was to evaluate the prevalence of MetS in patients with RA and to evaluate the relationship between MetS and clinical parameters, cardiovascular risk factors, and disease activity scores.


  Methods Top


Study design

In this cross-sectional study, we recruited a sample of women and men with RA who were scheduled for regular follow-ups in outpatients and inpatients in the Rheumatology Department of Charles Nicolle Hospital in Tunis (Tunisia) between March 2016 and May 2017.

Subjects were eligible for this study if their ages were up to 18 and they had been diagnosed with RA according to ACR/EULAR 2010 criteria.

Ethical concerns

The local committee of Charles Nicolle Hospital approved the study. A written informed consent was obtained from all patients before any data was collected.

Measurements

We collected the following data: history, disease duration, comorbidities, habits (smoking and sedentary lifestyle), family history of CVD (The presence of CVD in first-degree relatives, for women under 65 years or men under 55 years), and treatment: nonsteroidal anti-inflammatory drug (NSAIDs), corticosteroids, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and biologic DMARDs (bDMARDs).

Physical examination included swollen and tender joint count, blood pressure, waist circumference (WC), and body mass index (BMI). Normal BMI was defined as per the World Health Organization as 18.5–24.9 kg/m2, overweight as 25–29.9 kg/m2, and obesity as ≥30 kg/m2.

Disease activity was evaluated by the Disease Activity Score in 28 joints (DAS28), the Clinical Disease Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI).

Laboratory tests included complete blood count, rheumatoid factor (ELISA method), fasting glucose, lipid profile, C-reactive protein (CRP) (mg/L), and erythrocyte sedimentation rate (ESR) (mm).

The modified sharp score was used to quantify the radiological damage on hand and foot.[7]

To evaluate the cardiac risk, we used the HeartSCORE EULAR 2015 that evaluated the mortality risk in 10 years from CVDs. This score combines age, gender, total cholesterol (mmol/L), and systolic blood pressure (mmHg).[8] Patients are classified in a high or very high cardiovascular risk if the HeartSCORE is ≥5%, and in a moderate or low cardiovascular risk if the HeartSCORE is <5%.

Classification of metabolic syndrome

The National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) guidelines for MetS are the most widely used.[3] Patients are considered having MetS if they met at least three of the following:

  1. Central obesity defined as WC ≥102 cm for males and ≥88 cm for females
  2. Hypertension defined as blood pressure ≥130/85 mmHg (or treated for hypertension)
  3. Dyslipidemia defined as triglycerides ≥150 mg/dL or HDL <40 mg/dL for males and <50 mg/dL for females
  4. Fasting plasma glucose ≥110 mg/dL.


Patients were divided into two groups: with and without MetS.

Statistical analysis

The data were managed and analyzed with the software IBM SPSS Statistics version 11.5. IBM SPSS 20, The Program includes the following “ANTLR 2 License (a BSD-style license)” software: ANTLR 2.7.5 ANTLR 1989-2004 Developed by Terence Parr Partially supported by University of San Francisco & jGuru.com.

Clinical and demographic findings were expressed as mean values ± standard deviation for continuous variables or as frequencies and percentages for categorical variables. Patients were divided into two groups: with and without MetS.

Comparisons between these two groups were made with the Chi-square test or Fisher's exact test (categorical variables) and the Mann–Whitney test (continuous variables).

Logistic regression with “backward elimination” model was used to determine factors independently associated with MetS in RA patients. We included fators with significant association (P<0.05) and factors with 0.05<P < 0.1. Results were presented as odds ratios with 95% confidence interval. The level of statistical significance was set at 5% (P < 0.05) in all tests.


  Results Top


The study group consisted of 103 patients with RA. The mean age was 53 ± 10 years, and the sex ratio (Male/Female) was 0.3. The mean age at the time of the RA diagnosis was 43 ± 11.37 years. The mean DAS28 CRP score was 3.9 ± 1.38, and 45% of the patients had moderate disease activity. Half of the cases had low HAQ functional index (HAQ score ≥1). RA was erosive in 80% of the patients, and FR was positive in 79.6% of the cases. The characteristics of the RA patients are shown in [Table 1].
Table 1: Characteristics of the patients with rheumatoid arthritis

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Screening for cardiovascular risk factors revealed that 13% of the patients had a family history of CVD, 25% of the patients were either smokers or hypertensives, 18% had diabetes, 70% were obese or overweighted, and 14 patients had dyslipidemia. The ischemic ratio (CT/HDL-c) revealed that 42% of the patients had a moderate-to-high myocardial ischemic risk, and the estimation of the HeartSCORE EULAR 2015 was high or very high in 35% of the cases.

Metabolic syndrome components in rheumatoid arthritis patients

The prevalence of the MetS was 38.8%. The most prevalent MetS components according to NCEP/ATP III criteria were low HDL (53.4%) and increased WC (41.7%) [Table 2].
Table 2: Distribution of the metabolic syndrome components in patients with rheumatoid arthritis

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Rheumatoid arthritis patients with and without metabolic syndrome

RA patients with MetS were older (51.63 ± 11.03 years vs. 56.13 ± 8.6 years, P < 0.03), and their age of RA's onset was higher (40.8 years vs. 46.2 years; P = 0.01). Furthermore, MetS was significantly higher in postmenopausal women (38% vs. 55%; P = 0.006), in diabetes (8% vs. 35%; P = 0.01), in patients with family history of CVD (6.3% vs. 22.5%; P = 0.016), and with higher HeartSCORE (28.5% vs. 45%; P = 0.08) [Table 3].
Table 3: Characteristics of patients with rheumatoid arthritis and without metabolic syndrome

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However, patients with and without MetS did not differ significantly with regard to the gender, positivity of RF, mean disease duration, mean DAS28 scores (DAS28 ESR: 4.4 vs. 4.2; P = 0.79/DAS28 CRP: 3.9 vs. 3.8; P = 0.84), CDAI scores (17.8 vs. 16.1; P = 0.74), and SDAI scores (35.41 vs. 30.22; P = 0.4). Moreover, there was no difference between both groups concerning the treatment use (NSAIDs, csDMARDs, and bDMARDs) except the corticosteroid use which was higher in patient without MetS (87.3% vs. 67.5%; P = 0.01).

In laboratory tests, we did not found an association between the presence of MetS and inflammation (ESR and CRP) or immunologic parameters (RF and ACPA) [Table 4].
Table 4: Laboratory tests of rheumatoid arthritis patients with and without metabolic syndrome (the National Cholesterol Education Program/Adult Treatment Panel III)

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Variables independently associated with metabolic syndrome in rheumatoid arthritis patients

In the binary logistic regression with “backward elimination” model, we included age, age of disease onset, menopause, family history of CVD, and the current use of corticoid in the binary regression. Only menopause and family history of CVD were independently associated with MetS [Table 5].
Table 5: Parameters independently associated with metabolic syndrome in rheumatoid arthritis

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  Discussion Top


The prevalence of the MetS (NCEP/ATP III) in our study was 38.8%. We observed a high frequency of all MetS components, especially abdominal obesity, fasting glucose, and low HDL levels >50% of the cases. In another North African country study (Morocco), the prevalence of MetS was 32.4% (NCEP/ATP III),[9] similar to our study, while an Italian study reported 55.5% of MetS (NCEP/ATP III),[10] and in a Brazilian study, the prevalence was 51.3%. This differential of prevalence may be explained by differences in the profile of the population, including genetic factors, socioeconomic status, lifestyle, disease severity, and recruitment method. We should note that in our study, the mean age was 53 years, the mean disease duration was up to 10 years, and patients had moderate or high levels of inflammatory activity. These findings may have contributed to the high prevalence of MetS observed and it can be explained by the selection bias of the population as they were enrolled in a rheumatology department in a tertiary hospital.

Moreover, we notice that MetS was significantly associated with age of patients, family history of CVD, menopausal status of women, and age of the RA's onset.

Concerning treatments, the current use of corticosteroid was significantly associated with the MetS (P = 0.01) but not the dose prescribed nor the other treatments as csDMARDs and bDMARDs. These findings highlight the fact that corticosteroid should be stopped to reduce the MetS. These interesting findings support the notion of a specific profile of RA patients with MetS and suggest that more attention should be given to modifiable risk factors for RA patients, including dietary habits, physical activity, lipid profile, and corticosteroid use. We also found that menopause and family history of CVD were independently associated with MetS.

Our study showed that the cardiac risk stratification score (HeartSCORE) was significantly high in patients with MetS (P = 0.08). These findings confirm that RA patients have more cardiovascular risk factors and demonstrate the importance of the HeartSCORE to evaluate the risk of CVD in 10 years in RA patients. Indeed, according to the EULAR 2015 recommendations, the HeartSCORE should be multiplied by 1.5 for RA patients to not underestimate the risk of cardiovascular events like the Framingham score.[11]

Finally, chronic inflammation in long standing diseases like RA has an impact in the BMI and the MetS components. However, in our study the association were not significant between the presence of a MetS and inflammation and disease activity parameters. This may be explained by obesity and lipid paradox in RA. Baker JF et al.[12] illustrated this paradox in his study. Indeed, high disease activity can cause sarcopenia and decreases the BMI and LDL level which may contribute to the result that MetS components have no relation with disease activity and the inflammation parameters.

BMI in rheumatoid arthritis (RA) is a poor marker of metabolic and cardiovascular risk due to alterations in body composition and sarcopenic adiposity.

The distribution of metabolic syndrome (MetS) according to weight is still not understood in inflammatory rheumatism like rheumatoid arthritis. Unlike the general population a low body mass index is associated with an increased cardiovascular risk[12] and metabolic syndrome[13] in rheumatoid arthritis. There is other factors that are associated with the metabolic syndrome in non-obese subjects like the ratio of lean mass to fat mass. Indeed, the evaluation of body composition, measured by DXA, can be a predictor of the MetS. The ratio of lean mass to fat mass probably plays a role in the onset of cardio-metabolic co-morbidities in RA. Besides, Chung et al. demonstrated that inflammation promotes insulin resistance in both early RA and established RA, identifying inflammation as a causal factor of MetS.[14] Likewise, Stagakis et al. observed a positive correlation between high insulin resistance and high DAS28 values in RA patients.[15]

One of the advantages of this study was the simultaneous evaluation of multiple cardiovascular risk factors, disease characteristics, and laboratory parameters in RA patients. However, it has some limitations: first, the inflammatory state could change over time under treatment or later in disease progression and then cannot reflect the exact impact of inflammation on the MetS. Second, as it is a cross-sectional study, it is difficult to relate a unique estimation of the disease activity with a long-lasting process of the MetS.


  Conclusions Top


Our study revealed the profile of RA patients in North Africa, characterized by high prevalence of MetS and its independence of the disease activity level. Patients with MetS had a higher risk of CVD (HeartSCORE and ischemic ratio), indicating the need for better control of the modifiable risk factors for CVD. Future longitudinal studies are needed to observe the effect of disease status and control of modifiable risk factors on patient survival and quality of life.

Acknowledgments

We thank the Department of Rheumatology and Cardiology for assistance, access to patients, and for comments that greatly improved the manuscript. We would also like to show our gratitude to the department of biochemistry for facilitating the blood collection and fast results during this research.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Del Rincón ID, Williams K, Stern MP, Freeman GL, Escalante A. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum 2001;44:2737-45.  Back to cited text no. 1
    
2.
Mortality in a Large Cohort of Patients with Early Rheumatoid Arthritis That Were Treated-to-Target for 10 Years. ACR Meet Abstr. n.d. Available from: https://acrabstracts.org/abstract/mortality-in-a-large-cohort-of-patients-with-early-rheumatoid -arthritis-that-were-treated-to-target-for-10-years/. [Last accessed on 2020 Aug 08].  Back to cited text no. 2
    
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Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005;112:2735-52.  Back to cited text no. 3
    
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Pereira RM, de Carvalho JF, Bonfá E. Metabolic syndrome in rheumatological diseases. Autoimmun Rev 2009;8:415-9.  Back to cited text no. 4
    
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da Cunha VR, Brenol CV, Brenol JC, Fuchs SC, Arlindo EM, Melo IM, et al. Metabolic syndrome prevalence is increased in rheumatoid arthritis patients and is associated with disease activity. Scand J Rheumatol 2012;41:186-91.  Back to cited text no. 5
    
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Abourazzak FE, Mansouri S, Najdi A, Tahiri L, Nejjari C, Harzy T. Prevalence of metabolic syndrome in patients with rheumatoid arthritis in Morocco: A cross-sectional study of 179 cases. Clin Rheumatol 2014;33:1549-55.  Back to cited text no. 6
    
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Masson E. Évaluation radiographique dans la polyarthrite rhumatoïde: indices et critères. EM-Consulte n.d. https://www.em-consulte.com/article/245156/article/evaluation-radiographique-dans-la-polyarthrite-rhu [Last accessed on 2020 Aug 08].  Back to cited text no. 7
    
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Framingham Risk Score for Hard Coronary Heart Disease. MDCalc n.d. Available from: https://www.mdcalc.com/framingham-risk-score-hard-coronary-heart-disease. [Last accessed on 2020 Aug 08].  Back to cited text no. 8
    
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Rostom S, Mengat M, Lahlou R, Hari A, Bahiri R, Hajjaj-Hassouni N. Metabolic syndrome in rheumatoid arthritis: Case control study. BMC Musculoskelet Disord 2013;14:147.  Back to cited text no. 9
    
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Montagna GL, Cacciapuoti F, Buono R, Manzella D, Mennillo GA, Arciello A, et al. Insulin resistance is an independent risk factor for atherosclerosis in rheumatoid arthritis. Diab Vasc Dis Res 2007;4:130-5.  Back to cited text no. 10
    
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Arts EE, Popa C, Den Broeder AA, Semb AG, Toms T, Kitas GD, et al. Performance of four current risk algorithms in predicting cardiovascular events in patients with early rheumatoid arthritis. Ann Rheum Dis 2015;74:668-74.  Back to cited text no. 11
    
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Baker JF, Billig E, Michaud K, Ibrahim S, Caplan L, Cannon GW, et al. Weight loss, the obesity paradox, and the risk of death in rheumatoid arthritis. Arthritis Rheumatol 2015;67:1711-7.  Back to cited text no. 12
    
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Giraud C, Dutheil F, Lambert C, Soubrier M, Tournadre A. Division weight-dependent metabolic syndrome in polyarthritis rheumatoid and spondyloarthritis. RevRhum 2017;84:A55.  Back to cited text no. 13
    
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Chung CP, Oeser A, Solus JF, Avalos I, Gebretsadik T, Shintani A, et al. Prevalence of the metabolic syndrome is increased in rheumatoid arthritis and is associated with coronary atherosclerosis. Atherosclerosis 2008;196:756-63.  Back to cited text no. 14
    
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Stagakis I, Bertsias G, Karvounaris S, Kavousanaki M, Virla D, Raptopoulou A, et al. Anti-tumor necrosis factor therapy improves insulin resistance, beta cell function and insulin signaling in active rheumatoid arthritis patients with high insulin resistance. Arthritis Res Ther 2012;14:R141.  Back to cited text no. 15
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

 
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