CORRELATIVE STUDY BETWEEN LIPID PROFILE AND DISEASE ACTIVITY IN PATIENTS WITH RHEUMATOID ARTHRITIS – A HOSPITAL BASED STUDY

Dr. Sushma Yadav 1 , Prof Dr. R. K. Goswami 2 and Dr. Girindra Kumar Bora 3 . 1. M.O., MCD , New Delhi. 2. Former Prof and Head , Department Of Biochemistry, Assam Medical College and Hospital, Dibrugarh, Assam,786002. 3. Research Officer ( Biochemistry), RARI FOR GID, Guwahati, 781028. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History


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of TC and HDL-C during early active disease, and different patterns in established RA 4 . The inflammatory process that occurs in RA and the treatment factors may modify the lipid profile in these patients 5. Despite RA being the commonest inflammatory joint disease seen in India and evidence that cardiovascular disease and atherosclerotic manifestation as a common cause of death in patients with RA, little information is available on lipid levels in Indian patients with RA and in particular from the North Eastern region.
So keeping the above mentioned facts in mind, the present study was undertaken with the following aims and objectives. 1. Estimation of serum lipid in patients with Rheumatoid arthritis. 2. To study the correlation between serum lipid profile and disease activity in patients with Rheumatoid arthritis.

Materials and Methods:-
This case control study was conducted on cases of Rheumatoid arthritis who attended the Rheumatology clinic or were admitted in the Medicine wards of Assam Medical College and Hospital from August 2013 to September 2014.
Study population comprised of 50 cases of Rheumatoid arthritis .50 apparently healthy age and sex matched individuals were taken as controls. Attempt was made to take patients attendant or relative as control.
The study was conducted on cases of Rheumatoid arthritis diagnosed by 2010 Rheumatoid arthritis Classification Criteria: An American College of Rheumatology /European League Against Rheumatism Collaborative Initiative (ACR/EULAR 2010) 6 .Only those cases were included from whom informed consent could be taken.
Cases in remission were defined by the criteria laid by ACR/EULAR Provisional Definition of Remission in Rheumatoid arthritis 7 . Patients with score less than 2.6 were considered to be in remission while those with score more than or equal to 2.6 were with active disease.
Serum total cholesterol, triglyceride and HDL cholesterol were estimated enzymatically in semiautoanalyser using standard kits. LDL cholesterol was calculated using standard WHO approved formula (Friedewald's formula). ESR was measured by Westergren method. Quantitative estimation of CRP was done by Dimension RxL Max autoanalyser , Siemens.

Statistical analysis:-
The results were expressed in terms of percentage and mean ± SD (standard deviation). Analysis of results was done by unpaired Students t test. Pearsons coefficient of correlation was used to assess the relation between lipid profile and disease activity. Statistical analysis was done using Microsoft Excel 2007 and online software; Graphpad.

Results:-
The study comprised of fifty cases of RA and fifty apparently healthy controls. The cases were mostly clustered in the age group of 31-40 years (32%).The male: female ratio was seen to be 1:5 suggesting a higher preponderance in females. Of the 50 cases of rheumatoid arthritis, 13 cases were in remission and 37 cases had active disease according to the disease activity score (DAS 28 ESR).
As for serum triglyceride and VLDL, they were significantly higher (p<0.05) in cases than controls. LDL in cases was lower than controls, although not statistically significant.  The laboratory results of CRP showed that there was higher value of CRP (11.19±9.52 mg/dl) in RA patients than healthy control group (1.01±0.95 mg/dl) with the difference being very highly significant. .001 *** * Significant, ** highly significant, *** very highly significant The mean serum level of total cholesterol in active cases is 148.70 ± 11.42 mg/dl and in remission is 157.0± 12.61 mg/dl. T-test revealed significant difference in between the two groups showing that the total cholesterol in active cases is lower in comparison to cases in remission.(p<0.05) HDL level in cases in remission is 46.73±7.48 mg/dl and 39.92±6.28 mg/dl in active cases, thus signifying that HDL in active cases is low compared to those in remission. The difference is highly significant. (p<0.01) There was no significant difference in the levels of serum triglyceride, LDLc, and VLDLc in between active cases and those in remission.
There is very highly significant difference (p<0.001) in the CRP levels in the two groups.

Discussion:-
Our study was based on the estimation of serum lipid in 50 diagnosed cases of Rheumatoid arthritis and 50 apparently age and sex matched individuals who served as controls. Also the study was undertaken to find out any correlation between serum lipid profile and disease activity in patients with RA.
The male: female ratio was 1:5 thus signifying increased preponderance of RA in females. The findings are consistent with the study by Varunkumar et al (2013) 9 and Dessein et al (2002) 10 .
The laboratory results of CRP showed that RA patients had higher CRP levels (11.19±9.52 mg/dl) compared to healthy control group (1.01±0.95 mg/dl) with the difference being very highly significant. Active cases had a significantly higher CRP level than cases in remission (p<0.001). Georgiadis et al (2006) 11 in a case control study observed the CRP level of 28.15±20.75 mg/dl which was significantly higher than controls (2.1±1.3 mg/dl). In a study by Borman et al (1999) 12 on dyslipidemia in rheumatoid arthritis, the CRP level was found to be 18.25±14.03 mg/l in patients of rheumatoid arthritis. They also stated that active disease was associated with higher levels of CRP.
The serum total cholesterol (TC) in cases was 150.86± 12.18 mg/dl which was significantly lower (p<0.05) than controls (157.27±16.65 mg/dl). Further, in active cases the mean serum level of total cholesterol was significantly lower (p<0.05) than cases in remission. Vottery et al (2001) 13 compared the lipid profiles of 25 RA cases with age and sex matched controls. They observed that the total cholesterol was significantly lower in RA patients and in patients with active disease; the decrease in total cholesterol was significant in comparison to controls. Lazarevic et al (1992) 14 , Svenson et al(1987) 15 and Kim et al(2004) 16 also reported that the level of serum total cholesterol was y = -0.0606x + 6.1843  18 have observed that RA patients exhibited higher levels of serum total cholesterol in comparison to controls.
Serum triglyceride in our study was found to be 133.01±27.33 mg/dl in patients with RA which was higher when compared to controls (118.76 ± 39.11 mg/dl); the difference being statistically significant (p<0.05). Mahdi et al (2012) 19 and Vinapamula et al (2013) 5 also found that RA patients had significantly higher levels of serum triglyceride than controls (p<0.001 and p<0.05 respectively). Contrary to the above findings, some workers; Lakatos and Harsagyi (1988) 20 and Vottery et al (2001) 13 have found significantly lower level of serum triglyceride when compared to controls. However no significant difference was seen in levels of serum triglyceride in active cases and those in remission.
In the present study HDL cholesterol in cases was 41.7±7.20 mg/dl which was significantly lower (p<0.01) than controls (46.33 ± 7.60 mg/dl On comparing the levels of LDLc and VLDLc in between active cases and those in remission, there was no significant difference. On studying the correlation between lipid profile (TC, Triglyceride, HDLc, LDLc, VLDLc) and disease activity score (DAS 28-ESR), a significant negative correlation was seen between HDLc and DAS 28(r = -0.36, p<0.05). For total cholesterol, negative correlation(r= -0.17) was seen though not significant statistically. Mullick et al (2014) 22 found a significant inverse correlation between HDLc and DAS28(r = -0.35,p<0.01).
The overall findings of the present study were found to be at par or close to the findings of most of the earlier workers in this field. Our study reveals that the lipid profile is altered in Rheumatoid arthritis characterised by low total cholesterol (TC), HDL and elevated triglycerides. Futher, active disease was associated with lower levels of TC and HDL. An inverse correlation was seen between HDLc and disease activity (DAS 28); patients with high DAS-28 scores had lower values of HDLc.
The cause of the derangement in the lipid profile cannot be ascertained for sure. Inflammation as supported by high levels of CRP as well as disease activity might be responsible. Ernest Choy et al (2014) 23 have suggested that inflammation in RA could lead to lipid changes probably by suppression of the reticuloendothelial system and reduced low-density lipoprotein (LDL) particle synthesis. It is possible that under high inflammatory burden, excessive APR (acute phase reactants) production may impair trafficking of cholesterol in the liver or impede normal cholesterol production. Additionally, CRP mediates the uptake of LDL and oxidized LDL by macrophages, induces LDL deposition and increases LDL uptake by hepatocytes. The inflammatory burden in RA is associated with qualitative as well as quantitative changes in lipoproteins.

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RA is associated with increased levels of IL 6 and TNF α. IL-6 may lead to decreased levels of total cholesterol as suggested by Hashizume and Mihara(2011) 24 . TNF-α increases hepatic lipogenesis leading to hypertriglyceridemia (Steiner 2009) 25 . The reduced HDL-C in RA patients may be due to increased activity of cholesterol ester transfer protein (CETP) as hypothesised by Georgiadis et al(2006) 11 .

Conclusion:-
Our study reveals altered lipid profile in Rheumatoid Arthritis patients characterized by low total cholesterol, HDLc and elevated triglycerides. Further in active cases the mean serum level of total cholesterol was significantly lower than cases in remission. HDL cholesterol was significantly lower in active cases than those in remission. A significant negative correlation was seen between HDLc and DAS28.
Inflammation in RA is likely to alter the lipid profile in patients. Low HDL cholesterol is a strong predictor of cardiovascular events whereas raised triglycerides is atherogenic (Sattar et al) 26 .Cardiovascular morbidity and mortality is enhanced in RA and there is evidence that dyslipidemia is a risk factor.
However further studies with large sample size and longer duration might be of help to explore this area of RA in the light of autoimmunologic response so as to predict the alterations of the parameters assayed as predictive indices.