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Increase frequency of metabolic syndrome among the cases of rheumatoid arthritis: a case control study.

INTRODUCTION

It is well established that Rheumatoid Arthritis is associated with decreased life expectancy. While the absolute increase in mortality risk varies between studies, most found that majority of deaths result from cardiovascular disease. Traditional cardiovascular disease risk factors associated with atherosclerosis include age, smoking, hypertension and dyslipidemia. (1) Raised levels of systemic inflammation have also been shown to predispose both insulin resistance and type (2) Diabetes Mellitus (DM). (2) The metabolic syndrome which includes a constellation of metabolic abnormalities like central obesity, insulin resistance, glucose intolerance, dyslipidemia and hypertension. Each of these features is known to augment the risk of developing diabetes mellitus and cardiovascular disease. In view of the increased prevalence of vascular risk factors in patients with chronic inflammatory arthritis, the study was conducted to assess the prevalence of Metabolic Syndrome in patients with Rheumatoid Arthritis. (3)

METHODS AND MATERIALS

The present study is a cross-sectional observational study done in Assam Medical College and Hospital, Dibrugarh. The study was carried over a period of 1 year from 1st May 2011 to 30th April 2012. We have included all the patient of rheumatoid arthritis attending rheumatology OPD or admitted in the ward fulfilling the ACR/EULAR 2010 criteria and equal number of otherwise asymptomatic age and sex matched controls from the general population.

A total of 144 patients and healthy controls were enrolled in the study and were randomised into test and control groups. All patients of Rheumatoid Arthritis more than 12 yrs. of age, diagnosed by 2010 Rheumatoid Arthritis Classification Criteria An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative who attended Rheumatology clinics or admitted in Medicine Department of Assam Medical College and Hospital, Dibrugarh were included in the study. During the predetermined study period, 72 patients of Rheumatoid Arthritis were recruited for the study. Another 72 age and sex matched controls (1:1) were also included in the study. The statistical analysis was carried out using Statistical Package of Social Science (SSPS Inc., Chicago, IL, version 16.0 for window). All quantitative variables were estimated using measures of central location (Mean) and measures of dispersion (Standard deviation).

Categorical variables were compared by Chi Square test. Unpaired Student 't' test and ANOVA was applied for calculation of significance in difference of means. Pearson correlation was also calculated as appropriate. All statistical tests were two sided and performed at a significance level of [alpha] = 0.05.

RESULTS

The present study was conducted among 72 cases of Rheumatoid Arthritis who attended Rheumatology OPD or admitted in Dept. of Medicine of Assam Medical College and 72 age and sex matched comparable controls. Both the case and control groups were screened for presence of central obesity, hypertension, hyperglycemia and dyslipidemia. Metabolic syndrome was diagnosed in both study groups as per NCEP ATP III guidelines. The results are as follows:

The study population is comprised of 91.6% (n=66) female and 8.4% (n=6) male. The male:female in the study population is 1:11.

[FIGURE 1 OMITTED]

The study shows that majority of the participant group (33.33%) belonged to age group 40-<50 yrs. The mean age of the study population was 41.5 yrs.

[FIGURE 2 OMITTED]

The above table shows most of the patient (72.2%) in the study group has disease duration of less than 5 yrs. Out of which only 4 (5.6%) have early Rheumatoid Arthritis, i.e. [less than or equal to] 6 months in duration. The mean duration is 3.8 yrs.

(Results are expressed in mean [+ or -] standard deviation and in percentage as applicable). The history, clinical and laboratory characteristics of Rheumatoid Arthritis patients and controls are demonstrated in the above table. Patients with Rheumatoid Arthritis has surprisingly more HDL levels than the control group. The BMI when compared between two groups heavy weight (Prevention and Management of Obesity and Metabolic Syndrome in India; October 2008) subjects are found to be significantly high in the control group. There is significant difference seen in relation to systolic blood pressure, diastolic blood pressure in between the cases and controls.

Based on the NCP ATP III criteria 12(16.7%) patients and 5 (6.9%) controls has metabolic syndrome (p=0.07). Rheumatoid Arthritis patients and control groups are found to be different in hypertension (p=0.003) and low HDL (p=0.006) significantly, as hypertension was more common in cases whereas low HDL in controls.

There is no significant difference of the determinants of the disease process i.e. Rheumatoid arthritis in between the cases with metabolic syndrome and without metabolic syndrome.

From the above table it is found that the metabolic syndrome is more common among the Rheumatoid arthritis cases with disease duration <5yrs. However, there was no correlation found between metabolic syndrome and the duration of the disease (p=0.65).

DISCUSSION

The present study was done among the cases of Rheumatoid arthritis and their age, sex matched controls to find out the prevalence of metabolic syndrome in both groups and significant difference between them.

The interest in identifying metabolic syndrome in patients with Rheumatoid Arthritis has emerged recently, justified by the need to better understand the determinant factors of Cardiovascular Disease (CVD) in these patients.

In the present study, the sex ratio was 1:11 which is much higher than the normal (1:3), as it was not a population based study so this cannot be depicted as real sex ratio of Rheumatoid Arthritis. The age of maximum incidence in the study population was in between 40-<50 years, which is similar to the study by Alamanos Y et al. 2006.4 where disease incidence appeared to be greatest for women between 40 and 50 years of age and for men somewhat late. The minimum and maximum duration of Rheumatoid Arthritis in the present study was around 2 months and maximum was 25 years. Maximum number of the patient in the present study had disease duration less than 5 yrs. and mean duration was 3.8 years.

The prevalence of metabolic syndrome in Rheumatoid Arthritis patients is 16.7%> compared to 6.9% patients in the control groups as per NCEP-ATPIII guidelines, though the prevalence of metabolic syndrome in Rheumatoid Arthritis cases is two folds higher than the age and sex matched controls still it is not significant. This finding is in accordance with the results observed by Dessein et al. 2006. (5) La Montagna et al. 2007. (6) Marjenahkarimi et al. 2011. (7) In the present study one of the prominent finding was higher and significant prevalence of hypertension in Rheumatoid Arthritis patients as compared to controls, which was also observed by Antonio Naranjo et al. 2008 (QUEST RA Study). (8) and Mehmet Karakoca et al. 2012. (9) The prevalence of hypertension in the present study is 56.9%, which is very close to the observations made by Antonio Naranjo et al. 2008 (QUEST RA study). (8) where the prevalence for CV risk factors was 62.9% for hypertension.

Another striking observation made during the study is low HDL in controls (81.9) as compared to patients (61.1), which is recently supported by McMahon and colleagues. (10) They showed that pro-inflammatory HDL was detected more often in RA patients (n = 48) than in control subjects, (n = 72), i.e. 20% versus 4% respectively. (11) The most common form of dyslipidaemia in Rheumatoid Arthritis patients is the reduction of total HDL, LDL cholesterol and triglycerides. The use of corticosteroid independent of doses increases HDL levels. Endogenous glucocorticoid hormones regulate HDL concentration in the plasma by increasing synthesis and secretion of HDL by liver, therefore high level of exogenous glucocorticoid hormone, similar to those used in Rheumatoid Arthritis patients, probably accelerate this pathway. Thus in Rheumatoid Arthritis, the levels of HDL which were previously reduced increases, as a result a less atherogenic profile is induced may be due to the indirect effect of glucocorticoids.

The case with metabolic syndrome and without metabolic syndrome was compared and no significant difference is seen; however, a significant observation that was made during the study was, components of metabolic syndrome were manifested much earlier among the cases (39.25 years) as compared to controls (46.5 years). Around 7 years early, which is in consistent to certain extent with the findings of QUEST-RA. (8) study where around one decade early there was appearance of cardiovascular risk factors. The body weight of the controls with metabolic syndrome were significantly higher than the cases with metabolic syndrome. thus the occurrence of metabolic syndrome in controls can be attributed to adipose tissue.

While studying the relation between disease duration and prevalence of metabolic syndrome in Rheumatoid arthritis patients, there was no significant difference was seen when compared with cases without metabolic syndrome, which was in accordance with Mehmet Karakoc, et al. 2012. (9) This may be attributed to the fact that 72.2% of the present study population has a disease duration less than 5 yrs.

No significant difference were found regarding DAS28 index or other disease related factors and the presence or absence of metabolic syndrome in the present study even after taking disease activity as categorical variable, which is similar to Marjaneh Karimi et al. 2011 observation. (7) More ever relation between DAS 28 and prevalence of metabolic syndrome is conflicting. Study done by Mehmet Karakoca et al. (9) found that the prevalence of metabolic syndrome is higher in low disease activity group, whereas according to the study done by SA Karvounaris et al. (11) it is more common in high disease activity. It may be due to the masking of the inflammatory process by the ongoing drug treatment.

CONCLUSION

The present study was an initiative to know the complex interplay between Rheumatoid Arthritis and metabolic syndrome in this part of India where a pilot study is still lacking. The study observation shows that though there is no significant prevalence of metabolic syndrome among the cases of Rheumatoid Arthritis comparison to age and sex matched controls, but there is definite earlier presentation of metabolic syndrome among the cases, which has some implications as rheumatoid arthritis has less life expectancy than general population and the most common cause of death is cardiovascular diseases.

REFERENCES

(1.) Linos A, Worthington JW, O'Fallon WM, et al.: The epidemiology of Rheumatoid arthritis in Rochester, Minnesota: a study of incidence, prevalence and Mortality. Am J Epidemiol 1980;111:87.

(2.) Svenson KL, Pollare T, Lithel H, et al. Impaired glucose handling in active Rheumatoid Arthritis: relationship to peripheral insulin resistance. Metabolism 1988;37:125-30.

(3.) Chung CP, Oesar A, Shintani A, et al. Prevalence of metabolic syndrome is increased in Rheumatoid Arthritis and is associated with coronary atherosclerosis. Atherosclerosis 2008;196(2):756-63.

(4.) Alamanos Y, Voulgari PV, Drosos AA. Incidence and prevalence of Rheumatoid Arthritis, based on the 1987 American College of Rheumatology criteria: a systematic review. Semin Arthritis Rheum 2006;36:182-8.

(5.) Dessein PH, Tobias M, Veller MG: Metabolic syndrome and subclinical atherosclerosis in Rheumatoid arthritis. J Rheumatol 2006;33(12):2425-32.

(6.) La Montagna G, 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 Vase Dis Res. 2007 Jun;4(2):130-5.

(7.) Marnejah Karimi, Saeidh Mazloomdeh, Samira Kafan, et al. The frequency of metabolic syndrome in women with Rheumatoid Arthritis and in controls: International journal of Rheumatic disease 2011;14:248-2.

(8.) Antonio Naranjo, Tuulikki Sokka, Miguel A Descalzo, et al. for the QUEST-RA Group Cardiovascular disease in patients with Rheumatoid Arthritis: results from the QUEST-RA study Arthritis Research & Therapy 2008, 10;R30(doi:10.1186/ar2383).

(9.) Mehmet Karakoc, Ibrahim Batmaz, Mustafa AkifSariyildiz, Mehmet Tahtasiz, aRemziCevik, EbruTekbas, et al. The relationship of metabolic syndrome with disease activity and the functional status in patients with Rheumatoid Arthritis. J Clin Med Res. 2012 Aug;4(4):279-285.

(10.) McMahon M, Grossman J, FitzGerald J, Dahlin-Lee E, Wallace DJ, Thong BY, et al. Pro-inflammatory high-density lipoprotein as a biomarker for atherosclerosis in patients with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum. 2006 Aug;54(8):2541-9.

(11.) Karvounaris SA, Sidiropoulos PI, Papadakis JA, Spanakis EK, Bertsias GK, Kritikos HD, et al. Metabolic syndrome is common among middle-to-older aged Mediterranean patients with Rheumatoid Arthritis and correlates with disease activity: a retrospective, cross-sectional, controlled, study. Ann Rheum Dis 2007;66(l):28-33.

Prasanta Dihingia [1], Diganta Das [2], Arpita Chakraborty [3], Mahendra Debbarma [4], Sanjeeb Kakati [5]

[1] Associate Professor, Department of Medicine, Assam Medical College & Hospital, Dibrugarh.

[2] Registrar, Department of Medicine, Assam Medical College & Hospital, Dibrugarh.

[3] Senior Resident, Department of Medicine, Assam Medical College & Hospital, Dibrugarh.

[4] Junior Resident, Department of Medicine, Assam Medical College & Hospital, Dibrugarh.

[5] Professor, Department of Medicine, Assam Medical College & Hospital, Dibrugarh.

Financial or Other, Competing Interest: None.

Submission 07-12-2015, Peer Review 08-12-2015, Acceptance 07-01-2016, Published 11-01-2016.

Corresponding Author:

Diganta Das, Department of Medicine, Assam Medical College & Hospital, Dibrugarh-786002, Assam.

E-mail: drprashantadihingia@gmau.com drdigantadas@gmail.com

DOI: 10.14260/jemds/2016/47
Table 1: Sex Distribution of the Study

  Sex      Cases    Percentage

Female      66         91.6
Male         6         8.4
Total       72         100

Table 2: Age Distribution in the Cases

Age Group                       No. ot Cases   Percentage

12-<20                               2            2.8
20-<30                               8            11.2
30-<40                               21           29.1
40-<50                               24           33.3
50-<60                               13           18.0
[greater than or equal to] 60        4            5.6
Total                                72           100%

Table 3: Rheumatoid Arthritis
Cases According To Duration

Duration (Years)   Cases    Percentage

< 5                  52        72.2
5-10                 18        25.0
>10                  2         2.8
TOTAL                72        100%

Table 4: Comparison of History, Clinical, Laboratory
Characteristics of Cases and Controls

            CRITERIA                     CASES

SIGNIFICANT FAMILY HISTORY             15 (20.8%)
BODY WT (KG]                       55.4 [+ or -] 8.4
BMI
<18.4                                   2 (2.8%)
18.4-22.9                              27 (37.5%)
23-24.9                                20 (27.8%)
[greater than or equal to] 25          23 (31.9%)
WAIST                               51 [+ or -] 14.6
SYSTOLIC BP                         142[+ or -] 13.8
  [greater than or equal to] 130
DIASTOLIC BP                        92.9[+ or -] 5.7
  [greater than or equal to] 85
HIGH DENSITY LIPOPROTEIN            47 [+ or -] 14.6
TRIGLYCERIDES                       111 [+ or -] 40

            CRITERIA                    CONTROL         P VALUE

SIGNIFICANT FAMILY HISTORY             11 (15.2%)        0.383
BODY WT (KG]                       56.3 [+ or -] 6.3     0.422
BMI
<18.4                                    0 (0%]          0.15
18.4-22.9                              23 (31.9%]        0.48
23-24.9                                35 (48.6%]        0.01
[greater than or equal to] 25          14 (19.4%]        0.08
WAIST                              52.9 [+ or -] 14.6    0.436
SYSTOLIC BP                         134.4 [+ or -] 5    <0.000
  [greater than or equal to] 130
DIASTOLIC BP                        89 [+ or -] 4.6     <0.000
  [greater than or equal to] 85
HIGH DENSITY LIPOPROTEIN            37.8 [+ or -] 19     0.001
TRIGLYCERIDES                      99.9 [+ or -] 39.7    0.967

Table 5: Frequencies of Metabolic Syndrome
and Its Criteria in Cases and Control

    NCEP CRITERIA          CASES        CONTROL       P
                          (n=72)        (n=72)      VALUE

WAIST CIRCUMFERENCE      6 (8.3%)       1(1.3%)      0.05
HYPERTENSION             41 (56.9)    26 (36.1%)     0.01
HYPERGLYCEMIA            18 (25%)     17 (23.6%)     0.87
LOW HDL                 43 (59.7%)    59 (81.9%)    0.006
HYPERTRYGLYCERIDEMIA     4 (5.5%)      9 (11.1%)     0.09
METABOLIC SYNDROME      12 (16.7%)     5 (6.9%)      0.07

Table 6: Determinants of Rheumatoid Arthritis among
Patients with Metabolic Syndrome and Without Metabolic
Syndrome

                                                    WITHOUT
                          WITH METABOLIC           METABOLIC
    DETERMINANTS             SYNDROME           SYNDROME (n=60)

AGE                    39.25 [+ or -] 12.5      41.9 [+ or -] 11
DURATION                  3.6 [+ or -] 3        3.8 [+ or -] 3.9
DAS28                   4.2 [+ or -] 0.83       4.3 [+ or -] 1.4
ESR                     55.83 [+ or -] 19      54.9 [+ or -] 22.1
RF POSITIVE                  8 (66%)               35 (58.3%)
DURATION OF STEROID      2.5 [+ or -] 2.3       2.7 [+ or -] 2.7

    DETERMINANTS       P VALUE

AGE                     0.458
DURATION                0.730
DAS28                   0.602
ESR                     0.891
RF POSITIVE             0.589
DURATION OF STEROID     0.811

Table 7: Metabolic Syndrome In
Relation to Duration of Disease

DURATION    CASES WITH    CASES WITHOUT   TOTAL
(YRS)        METABOLIC      METABOLIC
             SYNDROME       SYNDROME

<5           8 (66.7%)     44 (73.3%)      52
5-10         4 (33.3%)     14 (23.3%)      18
>10              0          2 (3.4%)        2
TOTAL           12             60          72

Fig. 3 Metabolic Syndrome in Relation
To Duration of Disease

                                            <5     5-10   >10

Cases with metabolic Syndrome               66.7   33.3   0
Cases without Metabolic Syndrome Syndrome   73.3   23.3   2.4

Note: Table made from bar graph.
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Title Annotation:Original Article
Author:Dihingia, Prasanta; Das, Diganta; Chakraborty, Arpita; Debbarma, Mahendra; Kakati, Sanjeeb
Publication:Journal of Evolution of Medical and Dental Sciences
Article Type:Report
Date:Jan 11, 2016
Words:2748
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