|MEDICAL SCIENCE - RESEARCH ARTICLE
|Year : 2015 | Volume
| Issue : 5 | Page : 22-25
A comparative study on serum lipoprotein (a) and lipid profile between rheumatoid arthritis patients and normal subjects
KP Shiva Govindan1, Saleem Basha1, V Ramesh2, C Naveen Kumar2, S Swathi3
1 Department of Biochemistry, Melmaruvathur Adhiparasakthi Institute of Medical Science and Research, Melmaruvathur, India
2 Department of Biochemistry, Sri Lakshmi Narayana Institute of Medical Sciences, Puducherry, Affiliated to Bharath University, India
3 Department of Microbiology, Madha Dental College, Chennai, Tamil Nadu, India
|Date of Submission||31-Oct-2014|
|Date of Decision||31-Oct-2014|
|Date of Acceptance||09-Nov-2014|
|Date of Web Publication||30-Apr-2015|
Dr. V Ramesh
Department of Biochemistry, Sri Lakshmi Narayana Institute of Medical Sciences, Puducherry, Affiliated to Bharath University
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Rheumatoid arthritis is a chronic and systemic inflammatory disorder, in which Lipoprotein (a) [Lp (a)] increases plaque formation and thus promotes atherosclerosis. Coronary artery disease is one of the co-morbidity in rheumatoid arthritis patients. Aim: The aim of this study is to evaluate Lp (a) as a cardiovascular risk factor in patients with rheumatoid arthritis. This was a comparative study in which Lp (a) and lipid profile were compared in rheumatoid arthritis patients and controls. Materials and Methods: The study included 30 sero-positive rheumatoid arthritis patients and 30 normal healthy subjects with an age and sex matched group of 25-80 years. Statistical analysis was performed using SPSS version 17. Results: Serum Lp (a) concentration was significantly increased (P < 0.001) in rheumatoid arthritis patients compared with controls. Serum high-density lipoprotein-cholesterol was significantly lowered (P < 0.05) in patients as compared to controls. There was no significant difference in serum total cholesterol, triglycerides, and very low density lipoprotein-cholesterol between patients and controls. Conclusion: The findings indicate that the patients with rheumatoid arthritis are at high risk of developing cardiovascular disease in future due to the increased level of Lp (a). In addition to conventional lipid profile, estimation of Lp (a) can prove to be a valuable tool in risk assessment of population in general and management of disease in particular.
Keywords: Cardiovascular disease, lipoprotein (a), rheumatoid arthritis, lipid profile
|How to cite this article:|
Shiva Govindan K P, Basha S, Ramesh V, Kumar C N, Swathi S. A comparative study on serum lipoprotein (a) and lipid profile between rheumatoid arthritis patients and normal subjects. J Pharm Bioall Sci 2015;7, Suppl S1:22-5
|How to cite this URL:|
Shiva Govindan K P, Basha S, Ramesh V, Kumar C N, Swathi S. A comparative study on serum lipoprotein (a) and lipid profile between rheumatoid arthritis patients and normal subjects. J Pharm Bioall Sci [serial online] 2015 [cited 2021 May 9];7, Suppl S1:22-5. Available from: https://www.jpbsonline.org/text.asp?2015/7/5/22/155767
Rheumatoid arthritis is a chronic and systemic inflammatory disorder, which principally attacks synovial joints. It causes symmetric polyarthritis involving smaller and larger joints and extra-articular manifestations. Rheumatoid arthritis is associated with increased cardiovascular events including cardiac insufficiency, acute myocardial infarction and stroke.  It was said that the release of pro-inflammatory cytokines and acute phase proteins are responsible for atherosclerosis.  Cardiovascular disease (CVD) in rheumatoid arthritis patients accounts for 35% to 51% of all mortality.  Lipoprotein (a) [Lp (a)] is a low-density lipoprotein (LDL) - like particle, which has apolipoprotein (A) [apo (A)] attached to apolipoprotein (B) [apo (B)] molecule via disulfide bond. There are 34 different Lp (a) isoforms depending on the size of apo (A). Lp (a) levels are influenced by apo (A) polymorphism. 
Apolipoprotein (A) has a high degree homology with plasminogen and competes with plasminogen for fibrin binding sites and inhibits fibrinolysis. This increases plaque formation and thus promotes atherosclerosis. In addition to its role as a cholesterol carrier, Lp (a) involved in both inflammation and thrombosis. Lp (a) was significantly associated with acute phase proteins and was found to promote proliferation of vascular smooth muscle cells and chemotaxis of human monocytes. Its role in atherosclerosis was suggested by the structure of apo (A).  Small dense lipoprotein particle also plays an important role in the atherogenic process. Small dense LDL particles are much more atherogenic than large dense LDL particle, which are easily oxidized with lower binding affinity for LDL receptors. 
Atherosclerotic factors such as Lp (a) (or) triglyceride (TG) (or) decreased high-density lipoprotein (HDL) are involved in the atherosclerotic process. Increase in TGs an atherogenic factor, hypertriglyceridemia serve as marker for coronary artery disease (CAD).  Lp (a) significantly increased in myocardial infarction, which is the better marker for CAD.  Lp (a), exert independent, strong atherogenic effects.  Hence, we conducted a study to analyze the concentrations of serum Lp (a) in patients with active rheumatoid arthritis.
| Materials and Methods|| |
The study was conducted at SRM Medical College Hospital and Research Centre, SRM Nagar, Potheri, Tamil Nadu. The study was approved by Institutional Human Ethical Committee. An informed written consent was taken from subjects and healthy controls. Thirty subjects with sero-positive rheumatoid arthritis of both genders with the age group between 25 and 80 years were considered as cases. Age- and sex-matched thirty subjects without rheumatoid arthritis was considered as controls. Patients with history of diabetes, hypertension, obesity, renal failure, liver failure and family history of hyperlipidemia, those who were on treatment with lipid-lowering agents, smoking and alcohol use were excluded from the study.
Fasting blood samples were collected from healthy subjects and patients with the sero-positive rheumatoid arthritis. Lp (a) was analyzed by immunoturbidimetry using Merk Micro lab 300 Semi-auto analyzer, ELItech Group, ELI Tech group, 9 2800 Puteaux, France. Serum total cholesterol (TC) (cholesterol oxidase method), TG (glycerol phosphate oxidase-peroxidase method) and HDL-C (precipitation assay method) were estimated by using standard enzyme kits in OLYMPUS AU 400 auto analyzer (Wendenstrabe Hamburg, Germany) on the same day of collection. LDL-C, very low density lipoprotein-cholesterol (VLDL-C) were calculated by friedewald's formula.
All the data obtained were presented as mean ± standard deviation (SD). Comparisons were made between the rheumatoid arthritis patients and healthy subjects by using un-paired Student's t-test. "P" value of < 0.05 was considered as significant statistically. Correlation of Lp (a) and lipid profile were calculated by Pearson's correlation. All the statistical analyses were performed using SPSS for Microsoft Windows, version 17.0, IBM, International.
| Results|| |
[Table 1] shows a comparison of serum Lp (a) and serum lipid profile in rheumatoid arthritis patients and healthy subjects. The mean ± SD of serum Lp (a) levels in rheumatoid arthritis patients was significantly higher than that of healthy subjects (P < 0.001). There was a statistically significant reduction in the concentration of serum HDL-C between rheumatoid arthritis patients and healthy subjects (P < 0.05). There was no statistically significant difference (P > 0.05) were observed in parameters such as serum TC, TG, LDL-C, VLDL-C between the rheumatoid arthritis patients and healthy subjects.
|Table 1: Comparison of mean±SD of serum Lp (a) and lipid profile in sero-positive rheumatoid arthritis patients and healthy subjects|
Click here to view
In our study, the ratios of TC/HDL-C and LDL-C/HDL-C were significantly higher (P < 0.05) in rheumatoid arthritis patients than healthy subjects. Serum Lp (a) correlated negatively with HDL-C, (r = −0.435) (P = 0.0016).
| Discussion|| |
In our study, the serum concentration of Lp (a) was significantly increased in patients with rheumatoid arthritis. As an increased concentration of Lp (a) has been found to be closely associated with cardiovascular disease.  Lp (a) was an important cause of cardiovascular disease in patients with rheumatoid arthritis.
Rantapää-Dahlqvist et al. found that the Lp (a) level in rheumatoid arthritis patients was higher than in healthy subjects.  We also observed the same results. The effects of the inflammatory process on Lp (a) metabolism are unclear. It was suggested that increased synthesis and/or decreased destruction of Lp (a) or changes in Lp (a) distribution between intravascular and extravascular regions may cause dyslipoproteinemia in rheumatoid arthritis. 
Since the lipid contents of Lp (a) and LDL-C were similar, they might have similar mechanisms in atherosclerosis. It is suggested that the reticulo-endothelial system became over stimulated in active rheumatoid arthritis and then the lipid elimination by scavenger receptors of macrophages increased. For that reason, Lp (a) may have a role as an important atherogenic factor.  Dyslipoproteinemia in rheumatoid arthritis includes lower HDL-C, higher Lp (a), and higher TG and is related to atherosclerosis.  Our study also showed that lower HDL-C, higher Lp (a) and higher TG in rheumatoid arthritis. Lazarevic et al. established that HDL-C levels were lower in rheumatoid arthritis patients having antilipoprotein antibodies.  In our study also, there was a significant (P < 0.05) reduction in serum HDL-C level in rheumatoid arthritis patients. This significant difference in HDL-C level between rheumatoid arthritis patients and healthy subjects might be due to physical inactivity in the former.  Due to our rheumatoid arthritis patients had active-phase rheumatoid arthritis with various degrees of physical inactivity, in our study there was a significant reduction in serum HDL-C level. Lakatos et al. found that there were higher serum TC and LDL-C levels and lower HDL-C and TG levels in rheumatoid arthritis patients than in healthy subjects. 
Lipoprotein (a) binds pro-inflammatory-oxidized phospholipids and is a preferential carrier of oxidized phospholipids.  Apo (A) component of Lp (a) inhibits the key positive feedback step involving conversion of plasmin-mediated Glu-plasminogen to Lys-plasminogen.  The prothrombotic, antifibrinolytic actions of apo (A) are expressed on one hand as inhibition of fibrinolysis with enhancement of clot stabilization and on the other as enhanced coagulation via the inhibition of tissue factor pathway inhibitor. 
A reduction in cardio protective HDL-C and increase in LDL-C exposes rheumatoid arthritis patients to higher risk of CVD.  Our study has also shown significant reduction in serum HDL-C level in rheumatoid arthritis patients. However in our study, we did not get a significant difference in serum total cholesterol, TGs, LDL-C and VLDL-C. This might be due to low number (30) in sample size. If we do this study in a large population and long-term study, this may give valuable observation.
Inflammation of rheumatoid arthritis begins with cardiovascular damage that is the early diagnosis for the increased risk of CVD. Tumor necrosis factor-α controls the inflammation and reduces the risk of CVD.  Lp (a) with high LDL-C strongly correlated with risk of coronary heart disease.  Elevated Lp (a) level with high LDL-C, low HDL-C and hypertension increased cardiovascular risk.  Increased risk of atherosclerosis in rheumatoid arthritis patients has an ultrasonic marker for early atherosclerosis.  Rheumatoid arthritis patients were found to have high levels of small dense LDL particles, and this was related to acute phase response.  High circulating levels of small dense LDL particles constitute another characteristic feature of the metabolic syndrome.  Furthermore, the acute phase response contributes to atherosclerosis through endothelial activation and interaction with pro-coagulant factor.  Rheumatoid-factor (RF) positive were having higher risk of heart failure than RF negative.  Rheumatoid arthritis patients with heart failure are related to diastolic dysfunction than without heart failure. The higher rates of heart failure in rheumatoid arthritis are due to preserved ejection fraction. 
| Conclusion|| |
Inflammatory process of rheumatoid arthritis simultaneously initiates cardiovascular damage and hence early diagnosis of rheumatoid arthritis is important along with the recognition of increased risk of cardiovascular disease. Lp (a) level may be used as a screening tool to define cardiovascular risk among this population.
Further study should be taken to overcome the following limitations.
- Inclusion of the samples from various geographical distribution and large sample size will give more information on lipid profiles
- Long-term follow-up study will give more validated results.
| References|| |
Solomon DH, Goodson NJ, Katz JN, Weinblatt ME, Avorn J, Setoguchi S, et al.
Patterns of cardiovascular risk in rheumatoid arthritis. Ann Rheum Dis 2006;65:1608-12.
Sattar N, McCarey DW, Capell H, McInnes IB. Explaining how "high-grade" systemic inflammation accelerates vascular risk in rheumatoid arthritis. Circulation 2003;108:2957-63.
Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA, et al.
The mortality of rheumatoid arthritis. Arthritis Rheum 1994;37:481-94.
Enas EA, Garg A, Davidson MA, Nair VM, Huet BA, Yusuf S. Coronary heart disease and its risk factors in first-generation immigrant Asian Indians to the United States of America. Indian Heart J 1996;48:343-53.
Anglés-Cano E, de la Peña Díaz A, Loyau S. Inhibition of fibrinolysis by lipoprotein (a). Ann N Y Acad Sci 2001;936:261-75.
Gardner CD, Fortmann SP, Krauss RM. Association of small low-density lipoprotein particles with the incidence of coronary artery disease in men and women. JAMA 1996;276:875-81.
Banoo H. Role of dyslipidaemia in cardiovascular diseases and the therapeutic benefits by the appropriate drugs. Rev Artic Orion 2001;8:76-85.
Angeline T, Aruna R, Ramadevi K, Mohan G, Jeyaraj N. Serum lipoprotein (a) and lipid profile in young South Indian patients with myocardial infarction. Indian J Clin Biochem 2003;18:103-6.
Dahlen GH. Lipoprotein (a) in relation to atherosclerotic diseases. In: Widhalm K, Naito HK, editors. Prog Clin Biol Res 1988;255:27-36.
Danesh J, Collins R, Peto R. Lipoprotein (a) and coronary heart disease. Meta-analysis of prospective studies. Circulation 2000;102:1082-5.
Rantapää-Dahlqvist S, Wållberg-Jonsson S, Dahlén G. Lipoprotein (a), lipids, and lipoproteins in patients with rheumatoid arthritis. Ann Rheum Dis 1991;50:366-8.
Ehnholm C, Garoff H, Renkonen O, Simons K. Protein and carbohydrate composition of Lp (a) lipoprotein from human plasma. Biochemistry 1972;11:3229-32.
Ross R. Atherosclerosis - An inflammatory disease. N Engl J Med 1999;340:115-26.
Dursunoglu D, Evrengül H, Polat B, Tanriverdi H, Cobankara V, Kaftan A, et al.
Lp (a) lipoprotein and lipids in patients with rheumatoid arthritis: Serum levels and relationship to inflammation. Rheumatol Int 2005;25:241-5.
Lazarevic MB, Vitic J, Myones BL, Mladenovic V, Nanusevic N, Skosey JL, et al.
Antilipoprotein antibodies in rheumatoid arthritis. Semin Arthritis Rheum 1993;22:385-91.
Lakatos J, Hárságyi A. Serum total, HDL, LDL cholesterol, and triglyceride levels in patients with rheumatoid arthritis. Clin Biochem 1988;21:93-6.
Tsimikas S, Brilakis ES, Miller ER, McConnell JP, Lennon RJ, Kornman KS, et al.
Oxidized phospholipids, Lp (a) lipoprotein, and coronary artery disease. N Engl J Med 2005;353:46-57.
Feric NT, Boffa MB, Johnston SM, Koschinsky ML. Apolipoprotein (a) inhibits the conversion of Glu-plasminogen to Lys-plasminogen: A novel mechanism for lipoprotein (a)-mediated inhibition of plasminogen activation. J Thromb Haemost 2008;6:2113-20.
Nordestgaard BG, Chapman MJ, Ray K, Borén J, Andreotti F, Watts GF, et al.
Lipoprotein (a) as a cardiovascular risk factor: Current status. Eur Heart J 2010;31:2844-53.
McEntegart A, Capell HA, Creran D, Rumley A, Woodward M, Lowe GD. Cardiovascular risk factors, including thrombotic variables, in a population with rheumatoid arthritis. Rheumatology (Oxford). 2001;40:640-4.
Briggs C, Pharm D. The relationship between rheumatoid arthritis and heart failure. J Manag Care Med 2011;12:35-40.
Agoston-Coldea L, Rusu LD, Zdrenghea D, Rusu ML, Pop D, Craciun A, et al.
Lipoprotein (a) and lipid and non-lipid risk factors in coronaries risk assessment. Rom J Intern Med 2008;46:137-44.
Noma A, Abe A, Maeda S, Seishima M, Makino K, Yano Y, et al.
Lp (a): An acute-phase reactant? Chem Phys Lipids 1994;67-68:411-7.
Park YB, Ahn CW, Choi HK, Lee SH, In BH, Lee HC, et al.
Atherosclerosis in rheumatoid arthritis: Morphologic evidence obtained by carotid ultrasound. Arthritis Rheum 2002;46:1714-9.
Hurt-Camejo E, Paredes S, Masana L, Camejo G, Sartipy P, Rosengren B, et al.
Elevated levels of small, low-density lipoprotein with high affinity for arterial matrix components in patients with rheumatoid arthritis: Possible contribution of phospholipase A2 to this atherogenic profile. Arthritis Rheum 2001;44:2761-7.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Executive summary of the third report of The National Cholesterol Education Program (NCEP) Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). J Am Med Assoc 2001;285:2486-97.
Wållberg-Jonsson S, Cederfelt M, Rantapää Dahlqvist S. Hemostatic factors and cardiovascular disease in active rheumatoid arthritis: An 8 year followup study. J Rheumatol 2000;27:71-5.
Nicola PJ, Maradit-Kremers H, Roger VL, Jacobsen SJ, Crowson CS, Ballman KV, et al.
The risk of congestive heart failure in rheumatoid arthritis: A population-based study over 46 years. Arthritis Rheum 2005;52:412-20.
Davis JM 3 rd
, Roger VL, Crowson CS, Kremers HM, Therneau TM, Gabriel SE. The presentation and outcome of heart failure in patients with rheumatoid arthritis differs from that in the general population. Arthritis Rheum 2008;58:2603-11.