A review on cardiovascular risk in rheumatoid arthritis


  • Ramya Balaprabha G. Department of Pharm D., CMR College of Pharmacy, Kandlakoya, Medchal, Hyderabad, Telangana, India
  • Sri Vaishnavi P. Department of Pharm D., CMR College of Pharmacy, Kandlakoya, Medchal, Hyderabad, Telangana, India
  • Harika Guptha M. Department of Pharm D., CMR College of Pharmacy, Kandlakoya, Medchal, Hyderabad, Telangana, India
  • Krishna Sree N. Department of Pharm D., CMR College of Pharmacy, Kandlakoya, Medchal, Hyderabad, Telangana, India
  • Rama Rao T. Department of Pharmacy, CMR College of Pharmacy, Kandlakoya, Medchal, Hyderabad, Telangana, India




Cardiovascular risk factors, RA, CVD, Anti-rheumatic medications, Cardiac risk management, Inflammatory mediators


A systemic inflammatory disease known as rheumatoid arthritis (RA) is distinguished by excessive cardiovascular disease (CVD) morbidity and death. Traditional CV risk factors may partially contribute to CV disease in RA. Shared inflammatory mediators, post-translational modifications of peptides/proteins and subsequent immune responses, changes in the composition and function of lipoproteins, increased oxidative stress, and endothelial dysfunction are some of the mechanisms that link RA and CVD. The detailed pathogenetic pathway by which this association between RA and CVD might be explained is still not entirely known. It is crucial for controlling cardiovascular risk in people with RA. Optimizing care of traditional risk factors in addition to those inherent to RA is necessary to lessen the burden caused by CVD. The potential effect of planned Cardiac risk management in these individuals is highlighted by findings for under diagnosis and inadequate treatment of conventional CVD risk factors in RA. Present cardiovascular standards suggest RA patients to be examined for and treated for CVD risk factors without appropriate treatment goals. Utilizing potent anti-rheumatic medications that can reduce disease activity and treating the conventional CV risk factors should both be part of the therapy of CV risk in RA. There is currently insufficient scientific data to develop therapy targets for RA-related CVD risk factors. Thus, more study is required on the traditional CVD risk factor screening and management in RA patients.


Aletaha D, Neogi T, Silman A, Julia F, David TF, Clifton OB 3rd, et al. 2010 rheumatoid arthritis classifi cation criteria: an American College of Rheumatology/ European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010;69(9):1580-88.

Maradit-Kremers H, Crowson CS, Nicola PJ, Ballman KV, Roger VL, Jacobsen J, et al. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheumatism. 2005;52(2):402-11.

Stevens RJ, Douglas KMJ, Saratzis AN. Inflammation and atherosclerosis in rheumatoid arthritis. Expert Rev Mol Med. 2005;7(7):1-24.

Avina-Zubieta JA, Thomas J, Sadatsafavi M, Lehman AJ, Lacaille D. Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies. Ann Rheum Dis. 2012;71(9):1524-9.

Sugiyama D, Nishimura K, Tamaki K, Tsuji G, Nakazawa T, Morinobu A, et al. Impact of smoking as a risk factor for developing rheumatoid arthritis: a meta-analysis of observational studies. Ann Rheum Dis. 2010;69(1):70e81.

Farragher T, Goodson N, Naseem H, Silman A, Thomson W, Symmons D, et al. Association of the HLA-DRB1 gene with premature death, particularly from cardiovascular disease, in patients with rheumatoid arthritis and inflammatory polyarthritis 5. Arthritis Rheum. 2008;58(2):359-69.

Sattar N, McCarey DW, Capell H, McInnes IB. Explaining how “high-grade” systemic infammation accelerates vascular risk in rheumatoid arthritis. Circulation. 2003;108(24):2957-63.

Safar ME, Asmar R, Benetos A, Blacher J, Boutouyrie P, Lacolley P, et al. Interaction between hypertension and arterial stifness: an expert reappraisal. Hypertension. 2018;72(4):796-805.

Kim JY, Lee EY, Park JK. Patients with rheumatoid arthritis show altered lipoprotein profiles with dysfunctional high-density lipoproteins that can exacerbate inflammatory and atherogenic process. PLoS One. 2016;11(10):e0164564.

Bag-Ozbek A, Giles JT. Inflammation, adiposity, and atherogenic dyslipidemia in rheumatoid arthritis: is there a paradoxical relationship? Curr Allerg Asthma Rep. 2015;15(2):497.

Tejera-Segura B, Macía-Díaz M, Machado JD, De Vera-González A, García-Dopico JA, Olmos JM, et al. HDL cholesterol efflux capacity in rheumatoid arthritis patients: Contributing factors and relationship with subclinical atherosclerosis. Arthritis Res. Ther. 2017;19:113.

Ajeganova S, Ehrnfelt C, Alizadeh R, Morteza R, Tomas J, Ingiäld H, et al. Longitudinal levels of apolipoproteins and antibodies against phosphorylcholine are independently associated with carotid artery atherosclerosis 5 years after rheumatoid arthritis onset–a prospective cohort study. Rheumatology. 2011;50(10):1785-93.

García-Gómez C, Bianchi M, De la Fuente D, Lina B, Teresa P, Emili C, et al. Inflammation, lipid metabolism and cardiovascular risk in rheumatoid arthritis: a qualitative relationship? World J Orthop. 2014;5(3):304-11.

Summers GD, Metsios GS, Stavropoulos-Kalinoglou A, Kitas GD. Rheumatoid cachexia and cardiovascular disease. Nat Rev Rheumatol. 2010;6(8):445.

Guttridge DC, Mayo MW, Madrid LV, Wang C-Y, Baldwin AS Jr. NF-κB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia. Science. 2000;289(5488):2363-6.

Stavropoulos-Kalinoglou A, Metsios GS, Panoulas VF, Nevill AM, Jamurtas AZ, Koutedakis Y, et al. Underweight and obese states both associate with worse disease activity and physical function in patients with established rheumatoid arthritis. Clin Rheumatol. 2009;28(4):439-44.

Pamuk ON, Unlü E, Cakir N. Role of insulin resistance in increased frequency of atherosclerosis detected by carotid ultrasonography in rheumatoid arthritis. J Rheumatol. 2006;33(12):2447-52.

Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11:85-97.

Gonzalez-Gay MA, Gonzalez-Juanatey C, Vazquez-Rodriguez TR, Miranda-Filloy JA, Llorca J. Insulin resistance in rheumatoid arthritis: the impact of the anti-TNF-alpha therapy. Ann N Y Acad Sci. 2010;1193:153-9.

Libby P. Infammation and cardiovascular disease mechanisms. Am J Clin Nutr. 2006;83(2):456S-60S.

Douglas KMJ, Pace AV, Treharne GJ, Saratzis A, Nightingale P, Erb N, et al. Excess recurrent cardiac events in rheumatoid arthritis patients with acute coronary syndrome. Ann Rheum Dis. 2006;65:348-53.

Corrales A, Dessein PH, Tsang L, Pina T, Blanco R, Gonzalez Juanatey C, et al. Carotid artery plaque in women with rheumatoid arthritis and low estimated cardiovascular disease risk: a cross-sectional study. Arthritis Res Ther. 2015;17(1):55.

Skeoch S, Cristinacce PH, Williams H, Pemberton P, Xu D, Sun J, et al. Imaging atherosclerosis in rheumatoid arthritis: evidence for increased prevalence, altered phenotype and a link between systemic and localized plaque inflammation. Sci Rep. 2017;7(1):1-12.

Koelemay MJ, Nederkoorn PJ, Reitsma JB, Majoie CB. Systematic review of computed tomographic angiography for assessment of carotid artery disease. Stroke. 2004;35(10):2306-12.

Del Rincón I, Williams K, Stern MP, Freeman GL, O’leary DH, Escalante A. Association between carotid atherosclerosis and markers of infammation in rheumatoid arthritis patients and healthy subjects. Arthritis Rheumatol. 2003;48(7):1833-40

Yayan J. Erythrocyte sedimentation rate as a marker for coronary heart disease. Vasc Health Risk Manag. 2012;8:219.

Cruickshank K, Riste L, Anderson SG, John SW, Graham D, Ray GG, et al. Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function? Circulation. 2002;106(16):2085Y2090.

O’Rourke MF, Staessen JA, Vlachopoulos C, Daniel D, Gérard EP. Clinical applications of arterial stiffness; definitions and reference values. Am J Hypertens. 2002;15(5):426Y444.

Laurent S, Cockcroft J, van Bortel L, Pierre B, Cristina G, Daniel H, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27(21):2588Y2605.

Donald AE, Charakida M, Cole TJ, Peter F, Phil JC, Sandrine CM, et al. Non-invasive assessment of endothelial function: which technique? J Am Coll Cardiol. 2006;48(9):1846Y1850.

Rumberger JA, Simons DB, Fitzpatrick LA, Sheedy PF, Schwartz RS, et al. Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area. A histopathologic correlative study. Circulation. 1995;92(8):2157Y2162.

Grundy SM, Stone NJ, Nailey AL, Craig B, Kim KB, Roger SB, et al. 2018 AHA/ACC/ AACVPR/AAPA/ABC/ACPM/ADA/AGS APhA/ASPC/NLA/ PCBA Guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. J Am College Cardiol. 2018;73(24):e285-e350.

Duerden M, O’Flynn N Qureshi N. Cardiovascular risk assessment and lipid modification: NICE guideline. British J GenPract. 2015;65(636):378-80

Mendis S, Lindholm LH, Mancia G, Whitworth J, Alderman M, Lim S, et al. World Health Organization (WHO) and International Society of Hypertension (ISH) risk prediction charts: assessment of cardiovascular risk for prevention and control of cardiovascular disease in low and middle-income countries. J Hypertens. 2007;25(8):1578-80.

Peters MJ, Symmons DP, McCarey D, Dijkmans BAC, Nicola P, Kvien TK, et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis. 2010;69(2):325e31.

Holmqvist ME, Wedren S, Jacobsson LT, Klareskog L, Nyberg F, Rantapää-Dahlqvist S, et al. Rapid increase in myocardial infarction risk following diagnosis of rheumatoid arthritis amongst patients diagnosed between 1995 and 2006. J Intern Med. 2006;268(6):578e85.

Finckh A, Courvoisier DS, Pagano S, Sylvette B, Chevallier-Ruggeri P, Hochstrasser D, et al. Evaluation of cardiovascular risk in patients with rheumatoid arthritis: do cardiovascular biomarkers offer added predictive ability over established clinical risk scores? Arthritis Care Res. 2012;64(6):817e25.

Wiersma T, Smulders YM, Stehouwer CD, Konings KT, Lanphen J. Summary of the multidisciplinary guideline on cardiovascular risk management (revision 2011). Ned Tijdschr Geneeskd. 2012;156:A5104.

Trelle S, Reichenbach S, Wandel S, Pius H, Beatrice T, Peter MV, et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011;342:c7086.

Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med. 2000;343(21):1520-28.

Verhoeven F, Prati C, Maguin-Gaté K, Daniel W, Céline D. Glucocorticoids and endothelial function in inflammatory diseases: focus on rheumatoid arthritis. Arthritis Res Ther. 2016;18(1):258.

Del Rincón I, Battafarano DF, Restrepo JF, John ME, Agustín E, et al. Glucocorticoid dose thresholds associated with all-cause and cardiovascular mortality in rheumatoid arthritis. Arthritis Rheumatol (Hoboken, NJ). 2014;66(2):264-72.

Dessein PH, Joffe BI, Stanwix AE, Christian BF, Veller M. Glucocorticoids and insulin sensitivity in rheumatoid arthritis. J Rheumatol. 2004;31(5):867-74.

Stavropoulos-Kalinoglou A, Metsios GS, Veldhuijzen van Zanten JJ, Nightingale P, Kitas GD, Koutedakis Y. Individualised aerobic and resistance exercise training improves cardiorespiratory fitness and reduces cardiovascular risk in patients with rheumatoid arthritis. Ann Rheum Dis. 2012;72(11):1819-25.

Estruch R, Ros E, Salas-Salvado J, Maria-Isabel C, Dolores C, Fernando A, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;368(25):1279e90.

Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr. 2002;21(6):495e505.

Abeles AM, Pillinger MH. Statins as anti-inflammatory and immunomodulatory agents: a future in rheumatologic therapy? Arthritis Rheum. 2006;54(2):393e407.

Ridker PM, Danielson E, Fonseca FA, Jacques G, Antonio MG Jr, John JPK, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195e207.

El-Barbary AM, Hussein MS, Rageh EM, Hamouda HE, Wagih AA, Ismail RG. Effect of atorvastatin on inflammation and modification of vascular risk factors in rheumatoid arthritis. J Rheumatol 2011;38:229e35.

Flammer AJ, Sudano I, Hermann F, Steffen G, Adrian F, Michel N, et al. Angiotensin-converting enzyme inhibition improves vascular function in rheumatoid arthritis. Circulation. 2008;117(17):2262e9.

Popa C, van den Hoogen FH, Radstake TR, Mihai GN, Agnes EE, Martin DH, et al. Modulation of lipoprotein plasma concentrations during long-term anti-TNF therapy in patients with active rheumatoid arthritis. Ann Rheum Dis. 2007;66(11):1503e7.

Angel K, Provan SA, Gulseth HL, Mowinckel P, Kvien TK, Atar D. Tumor necrosis factor-alpha antagonists improve aortic stiffness in patients with inflammatory arthropathies: a controlled study. Hypertension. 2010;55:333

Navarro-Millan I, Charles-Schoeman C, Yang S, Joan MB, Louis SB Jr, Lang C, et al. Changes in lipoproteins associated with methotrexate or combination therapy in early rheumatoid arthritis: results from the treatment of early rheumatoid arthritis trial. Arthritis Rheum. 2013;65(6):1430e8.

Hurlimann D, Forster A, Noll G, Frank E, Rémy C, Oliver D, et al. Anti-tumor necrosis factor-alpha treatment improves endothelial function in patients with rheumatoid arthritis. Circulation. 2002;106(17):2184e7.

Kerekes G, Soltesz P, Der H, Katalin V, Zoltán S, Anikó V, et al. Effects of rituximab treatment on endothelial dysfunction, carotid atherosclerosis, and lipid profile in rheumatoid arthritis. Clin Rheumatol. 2009;28(6):705e10.

Caligiuri G, Nicoletti A, Poirier B, Hansson GK. Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice. J Clin Invest. 2002;109(6):745e53.




How to Cite

G., R. B., P., S. V., M., H. G., Sree N., K., & Rao T., R. (2024). A review on cardiovascular risk in rheumatoid arthritis. International Journal of Basic & Clinical Pharmacology, 13(3), 425–432. https://doi.org/10.18203/2319-2003.ijbcp20241007



Review Articles