JOURNAL OF THE CZECH PHARMACEUTICAL SOCIETY AND THE SLOVAK PHARMACEUTICAL SOCIETY

Čes. slov. farm. 2019, 68(6):219-228 | DOI: 10.36290/csf.2019.027

Lipid profile and risks of cardiovascular diseases in conditions of rheumatoid arthritis

Ľudmila Pašková
Katedra bunkovej a molekulárnej biológie liečiv, Farmaceutická fakulta Univerzity Komenského, Bratislava, SR

Cardiovascular diseases (CVD) belong to the leading causes of mortality worldwide. Elevated levels of total cholesterol and LDL cholesterol are associated with increased incidence of CVD in the population. Reversely, reduction of lipoprotein levels in plasma results in a positive impact on CVD prevention. Patients with rheumatoid arthritis (RA), a chronic inflammatory disease, have markedly increased mortality risk due to CVD, despite lower lipoprotein levels in comparison with common population. This is known as the "lipid paradox". RA itself represents an independent CVD risk factor acting as an inflammatory component. Inflammation, manifested by systemic elevated concentrations of pro-inflammatory cytokines, mainly interleukin 6 (IL-6), interleukin 1β (IL-1β) and the tumour necrosis factor α (TNF-α) in RA, is considered to be the main contributor of atherogenesis via its impact on lipoprotein metabolism and on the biology of the arterial wall. Atherosclerosis, a complex process including a number of mechanisms, is not only regarded as dysregulation of lipid metabolism, but also as a chronic inflammatory disease. This review summarizes the newest findings about the qualitative and quantitative alterations of lipids and lipoproteins affected by low-grade inflammation triggered by RA and their consequences on atherosclerosis.

Keywords: Atherosclerosis; rheumatoid arthritis; inflammation; lipid metabolism; HDL
Grants and funding:

Práca bola podporovaná Agentúrou na podporu výskumu a vývoja prostredníctvom finančnej podpory č. 15-0308.

Received: September 19, 2019; Accepted: November 7, 2019; Published: June 1, 2019  Show citation

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Pašková Ľ. Lipid profile and risks of cardiovascular diseases in conditions of rheumatoid arthritis. Čes. slov. farm. 2019;68(6):219-228. doi: 10.36290/csf.2019.027.
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References

  1. Radovits B. J., Fransen J., Al Shamma S., Eijsbouts A. M., van Riel P. L., Laan R. F. Excess mortality emerges after 10 years in an inception cohort of early rheumatoid arthritis. Arthritis Care Res. (Hoboken) 2010; 62, 362-370. Go to original source... Go to PubMed...
  2. Holmqvist M. E., Wedrén S., Jacobsson L. T., Klareskog L., Nyberg F., Rantapää-Dahlqvist S., Alfredsson L., Askling J. Rapid increase in myocardial infarction risk following diagnosis of rheumatoid arthritis amongst patients diagnosed between 1995 and 2006. J. Intern. Med. 2010; 268, 578-585. Go to original source... Go to PubMed...
  3. Bergholm R., Leirisalo-Repo M., Vehkavaara S., Mäkimattila S., Taskinen M. R., Yki-Järvinen H. Impaired responsiveness to NO in newly diagnosed patients with rheumatoid arthritis. Arterioscler. Thromb. Vasc. Biol. 2002; 22, 1637-1641. Go to original source... Go to PubMed...
  4. Gisterå A., Hansson G. K. The immunology of atherosclerosis. Nat. Rev. Nephrol. 2017; 13, 368-380. Go to original source... Go to PubMed...
  5. Pincus T., Callahan L. F. Taking mortality in rheumatoid arthritis seriously-predictive markers, socioeconomic status and comorbidity. J. Rheumatol. 1986; 13, 841-845.
  6. Dessein P. H., Joffe B. I., Veller M. G., Stevens B. A., Tobias M., Reddi K., Stanwix A. E. Traditional and nontraditional cardiovascular risk factors are associated with atherosclerosis in rheumatoid arthritis. J. Rheumatol. 2005; 32, 435-442.
  7. Goodson N. J., Solomon D. H. The cardiovascular manifestations of rheumatic diseases. Curr. Opin. Rheumatol. 2006; 18, 135-140. Go to original source... Go to PubMed...
  8. Maradit-Kremers H., Nicola P. J., Crowson C. S., Ballman K. V., Gabriel S. E. Cardiovascular death in rheumatoid arthritis: a population-based study. Arthritis Rheum. 2005; 52, 722-732. Go to original source... Go to PubMed...
  9. González-Gay M. A., González-Juanatey C. Inflammation and lipid profile in rheumatoid arthritis: bridging an apparent paradox. Ann. Rheum. Dis. 2014; 73, 1281-1283. Go to original source... Go to PubMed...
  10. Asanuma Y., Kawai S., Aoshima H., Kaburaki J., Mizushima Y. Serum lipoprotein(a) and apolipoprotein(a) phenotypes in patients with rheumatoid arthritis. Arthritis Rheum. 1999; 42, 443-447. Go to original source...
  11. Steiner G., Urowitz M. B. Lipid profiles in patients with rheumatoid arthritis: mechanisms and the impact of treatment. Semin. Arthritis Rheum. 2009; 38, 372-381. Go to original source... Go to PubMed...
  12. Bergheanu S. C., Bodde M. C., Jukema J. W. Pathophysiology and treatment of atherosclerosis : Current view and future perspective on lipoprotein modification treatment. Neth. Heart J. 2017; 25, 231-242. Go to original source... Go to PubMed...
  13. Yang X., Li Y., Ren X., Zhang X., Hu D., Gao Y., Xing Y., Shang H. Oxidative Stress-Mediated Atherosclerosis: Mechanisms and Therapies. Front. Physiol. 2017; 8, 600. Go to original source... Go to PubMed...
  14. Ungurianu A., Margină D., Grădinaru D., Băcanu C., Ilie M., Tsitsimpikou C., Tsarouhas K., Spandidos D. A., Tsatsakis A. M. Lipoprotein redox status evaluation as a marker of cardiovascular disease risk in patients with inflammatory disease. Mol. Med. Rep. 2017; 15, 256-262. Go to original source... Go to PubMed...
  15. Smallwood M. J., Nissim A., Knight A. R., Whiteman M., Haigh R., Winyard P. G. Oxidative stress in autoimmune rheumatic diseases. Free Radic. Biol. Med. 2018; 125, 3-14. Go to original source... Go to PubMed...
  16. Arida A., Protogerou A. D., Kitas G. D., Sfikakis P. P. Systemic inflammatory response and atherosclerosis: The paradigm of chronic inflammatory rheumatic diseases. Int. J. Mol. Sci. 2018; 19. Go to original source... Go to PubMed...
  17. Sproston N. R., Ashworth J. J. Role of C-Reactive Protein at Sites of Inflammation and Infection. Front. Immunol. 2018; 9, 754. Go to original source... Go to PubMed...
  18. Robbins C. S., Hilgendorf I., Weber G. F., Theurl I., Iwamoto Y., Figueiredo J. L., Gorbatov R., Sukhova G. K., Gerhardt L. M., Smyth D., Zavitz C. C., Shikatani E. A., Parsons M., van Rooijen N., Lin H. Y., Husain M., Libby P., Nahrendorf M., Weissleder R., Swirski F. K. Local proliferation dominates lesional macrophage accumulation in atherosclerosis. Nat. Med. 2013; 19, 1166-1172. Go to original source... Go to PubMed...
  19. Hansson G. K., Libby P. The immune response in atherosclerosis: a double-edged sword. Nat. Rev. Immunol. 2006; 6, 508-519. Go to original source... Go to PubMed...
  20. Bäck M., Hansson G. K. Anti-inflammatory therapies for atherosclerosis. Nat. Rev. Cardiol. 2015; 12, 199-211. Go to original source... Go to PubMed...
  21. Plutzky J., Liao K. P. Lipids in RA: Is less not necessarily more? Curr. Rheumatol. Rep. 2018; 20, 8. Go to original source... Go to PubMed...
  22. Säemann M. D., Poglitsch M., Kopecky C., Haidinger M., Hörl W. H., Weichhart T. The versatility of HDL: a crucial anti-inflammatory regulator. Eur. J. Clin. Invest. 2010; 40, 1131-1143. Go to original source... Go to PubMed...
  23. Kerekes G., Soltész P., Dér H., Veres K., Szabó Z., Végvári A., Shoenfeld Y., Szekanecz Z. Effects of biologics on vascular function and atherosclerosis associated with rheumatoid arthritis. Ann. N. Y. Acad. Sci. 2009; 1173, 814-821. Go to original source... Go to PubMed...
  24. Kampoli A. M., Tousoulis D., Antoniades C., Siasos G., Stefanadis C. Biomarkers of premature atherosclerosis. Trends Mol. Med. 2009; 15, 323-332. Go to original source... Go to PubMed...
  25. Derić M., Stokić E., Kojić-Damjanov S., Cabarkapa V., Eremić N. Biochemical markers of atherosclerotic disease. Med. Pregl. 2009; 62(Suppl 3), 15-23.
  26. Khovidhunkit W., Kim M. S., Memon R. A., Shigenaga J. K., Moser A. H., Feingold K. R., Grunfeld C. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host. J. Lipid Res. 2004; 45, 1169-1196. Go to original source... Go to PubMed...
  27. Petrov I., Dumitrescu A., Snejdrlova M., Zafrir B., Wożakowska-Kapłon B., Fabryova L., Pintarić H., Bridges I., Petkova R. Clinical Management of High and Very High Risk Patients with Hyperlipidaemia in Central and Eastern Europe: An Observational Study. Adv. Ther. 2019; 36, 608-620. Go to original source... Go to PubMed...
  28. Sharrett A. R., Heiss G., Chambless L. E., Boerwinkle E., Coady S. A., Folsom A. R., Patsch W. Metabolic and lifestyle determinants of postprandial lipemia differ from those of fasting triglycerides: The Atherosclerosis Risk In Communities (ARIC) study. Arterioscler. Thromb. Vasc. Biol. 2001; 21, 275-281. Go to original source... Go to PubMed...
  29. Ye J. Mechanisms of insulin resistance in obesity. Front. Med. 2013; 7, 14-24. Go to original source... Go to PubMed...
  30. Manders R. J., van Dijk J. W., van Loon L. J. Low-intensity exercise reduces the prevalence of hyperglycemia in type 2 diabetes. Med. Sci. Sports Exerc. 2010; 42, 219-225. Go to original source... Go to PubMed...
  31. Henderson G. C., Fattor J. A., Horning M. A., Faghihnia N., Johnson M. L., Mau T. L., Luke-Zeitoun M., Brooks G. A. Lipolysis and fatty acid metabolism in men and women during the postexercise recovery period. J. Physiol. 2007; 584, 963-981. Go to original source... Go to PubMed...
  32. Plaisance, E. P., Fisher, G. Exercise and dietary-mediated reductions in postprandial lipemia. J. Nutr. Metab. 2014; 902065. Go to original source... Go to PubMed...
  33. Kim M. S., Shigenaga J., Moser A., Feingold K., Grunfeld C. Repression of farnesoid X receptor during the acute phase response. J. Biol. Chem. 2003; 278, 8988-8995. Go to original source... Go to PubMed...
  34. Hotamisligil G. S., Shargill N. S., Spiegelman B. M. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993; 259, 87-91. Go to original source... Go to PubMed...
  35. Hartman J., Frishman W. H. Inflammation and atherosclerosis: a review of the role of interleukin-6 in the development of atherosclerosis and the potential for targeted drug therapy. Cardiol. Rev. 2014; 22, 147-151. Go to original source... Go to PubMed...
  36. Fatkhullina A. R., Peshkova I. O., Koltsova E. K. The role of cytokines in the development of atherosclerosis. Biochemistry (Mosc) 2016; 81, 1358-1370. Go to original source... Go to PubMed...
  37. Vasanthi P., Nalini G., Rajasekhar G. Role of tumor necrosis factor-alpha in rheumatoid arthritis: a review. APLAR Journal of Rheumatology 2007. Go to original source...
  38. Chen X., Xun K., Chen L., Wang Y. TNF-alpha, a potent lipid metabolism regulator. Cell Biochem. Funct. 2009; 27, 407-416. Go to original source... Go to PubMed...
  39. Bensinger S. J., Bradley M. N., Joseph S. B., Zelcer N., Janssen E. M., Hausner M. A., Shih R., Parks J. S., Edwards P. A., Jamieson B. D., Tontonoz P. LXR signaling couples sterol metabolism to proliferation in the acquired immune response. Cell 2008; 134, 97-111. Go to original source... Go to PubMed...
  40. Reiss A. B., Siegart N. M., de Leon J. Interleukin-6 in atherosclerosis: atherogenic or atheroprotective? Clinical Lipidology 2017; 12, 14-23.
  41. Libby P. Role of inflammation in atherosclerosis associated with rheumatoid arthritis. Am. J. Med. 2008; 121, 21-31. Go to original source... Go to PubMed...
  42. Szalai A. J. The biological functions of C-reactive protein. Vascul. Pharmacol. 2002; 39, 105-107. Go to original source... Go to PubMed...
  43. Ridker P. M. High-sensitivity C-reactive protein and cardiovascular risk: rationale for screening and primary prevention. Am. J. Cardiol. 2003; 92, 17K-22K. Go to original source... Go to PubMed...
  44. Ridker P. M. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 2003; 107, 363-369. Go to original source... Go to PubMed...
  45. Sproston N. R., El Mohtadi M., Slevin M., Gilmore W., Ashworth J. J. The Effect of C-Reactive Protein Isoforms on Nitric Oxide Production by U937 Monocytes/Macrophages. Front. Immunol. 2018; 9, 1500. Go to original source... Go to PubMed...
  46. Zouridakis E., Avanzas P., Arroyo-Espliguero R., Fredericks S., Kaski J. C. Markers of inflammation and rapid coronary artery disease progression in patients with stable angina pectoris. Circulation 2004; 110, 1747-1753. Go to original source... Go to PubMed...
  47. Tölle M., Huang T., Schuchardt M., Jankowski V., Prüfer N., Jankowski J., Tietge U. J., Zidek W., van der Giet M. High-density lipoprotein loses its anti-inflammatory capacity by accumulation of pro-inflammatory-serum amyloid A. Cardiovasc. Res. 2012; 94, 154-162. Go to original source... Go to PubMed...
  48. Watanabe J., Charles-Schoeman C., Miao Y., Elashoff D., Lee Y. Y., Katselis G., Lee T. D., Reddy S. T. Proteomic profiling following immunoaffinity capture of high-density lipoprotein: association of acute-phase proteins and complement factors with proinflammatory high-density lipoprotein in rheumatoid arthritis. Arthritis Rheum. 2012; 64, 1828-1837. Go to original source... Go to PubMed...
  49. Navab M., van Lenten B. J., Reddy S. T., Fogelman A. M. High-density lipoprotein and the dynamics of atherosclerotic lesions. Circulation 2001; 104, 2386-2387. Go to original source...
  50. van Lenten B. J., Navab M., Shih D., Fogelman A. M., Lusis A. J. The role of high-density lipoproteins in oxidation and inflammation. Trends Cardiovasc. Med. 2001; 11, 155-161. Go to original source... Go to PubMed...
  51. Litvinov D., Mahini H., Garelnabi M. Antioxidant and anti-inflammatory role of paraoxonase 1: implication in arteriosclerosis diseases. N. Am. J. Med. Sci. 2012; 4, 523-532. Go to original source... Go to PubMed...
  52. Navab M., Berliner J. A., Subbanagounder G., Hama S., Lusis A. J., Castellani L. W., Reddy S., Shih D., Shi W., Watson A. D., van Lenten B. J., Vora D., Fogelman A. M. HDL and the inflammatory response induced by LDL-derived oxidized phospholipids. Arterioscler. Thromb. Vasc. Biol. 2001; 21, 481-488. Go to original source... Go to PubMed...
  53. Bowry V. W., Stanley K. K., Stocker R. High density lipoprotein is the major carrier of lipid hydroperoxides in human blood plasma from fasting donors. Proc. Natl. Acad. Sci. USA 1992; 89, 10316-10320. Go to original source... Go to PubMed...
  54. Besler C., Heinrich K., Rohrer L., Doerries C., Riwanto M., Shih D. M., Chroni A., Yonekawa K., Stein S., Schaefer N., Mueller M., Akhmedov A., Daniil G., Manes C., Templin C., Wyss C., Maier W., Tanner F. C., Matter C. M., Corti R., Furlong C., Lusis A. J., von Eckardstein A., Fogelman A. M., Lüscher T. F., Landmesser U. Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease. J. Clin. Invest. 2011; 121, 2693-2708. Go to original source... Go to PubMed...
  55. Charles-Schoeman C., Watanabe J., Lee Y. Y., Furst D. E., Amjadi S., Elashoff D., Park G., McMahon M., Paulus H. E., Fogelman A. M., Reddy S. T. Abnormal function of high-density lipoprotein is associated with poor disease control and an altered protein cargo in rheumatoid arthritis. Arthritis Rheum. 2009; 60, 2870-2879. Go to original source... Go to PubMed...
  56. Rosenson R. S., Brewer H. B., Ansell B. J., Barter P., Chapman M. J., Heinecke J. W., Kontush A., Tall A. R., Webb N. R. Dysfunctional HDL and atherosclerotic cardiovascular disease. Nat. Rev. Cardiol. 2016; 13, 48-60. Go to original source... Go to PubMed...
  57. Scott D. L., Wolfe F., Huizinga T. W. Rheumatoid arthritis. Lancet 2010; 376, 1094-1108. Go to original source... Go to PubMed...
  58. Kay J., Calabrese L. The role of interleukin-1 in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford) 2004; 43(Suppl 3), 32-39. Go to original source... Go to PubMed...
  59. Cavagna L., Boffini N., Cagnotto G., Inverardi F., Grosso V., Caporali R. Atherosclerosis and rheumatoid arthritis: more than a simple association. Mediators Inflamm. 2012; 2012, 147354. Go to original source... Go to PubMed...
  60. Arias de la Rosa I., Escudero-Contreras A., Rodríguez-Cuenca S., Ruiz-Ponce M., Jiménez-Gómez Y., Ruiz-Limón P., Pérez-Sánchez C., Ábalos-Aguilera M. C., Cecchi I., Ortega R., Calvo J., Guzmán-Ruiz R., Malagón M. M., Collantes-Estevez E., Vidal-Puig A., López-Pedrera C., Barbarroja N. Defective glucose and lipid metabolism in rheumatoid arthritis is determined by chronic inflammation in metabolic tissues. J. Intern. Med. 2018; 284, 61-77.
  61. Skeoch S., Bruce I. N. Atherosclerosis in rheumatoid arthritis: is it all about inflammation? Nat. Rev. Rheumatol. 2015; 11, 390-400. Go to original source... Go to PubMed...
  62. Vasanthi P., Nalini G., Rajasekhar G. Status of oxidative stress in rheumatoid arthritis. Int. J. Rheum. Dis. 2009; 12, 29-33. Go to original source... Go to PubMed...
  63. Roubenoff R., Dellaripa P., Nadeau M. R., Abad L. W., Muldoon B. A., Selhub J., Rosenberg I. H. Abnormal homocysteine metabolism in rheumatoid arthritis. Arthritis Rheum. 1997; 40, 718-722. Go to original source... Go to PubMed...
  64. Stühlinger M. C., Tsao P. S., Her J. H., Kimoto M., Balint R. F., Cooke J. P. Homocysteine impairs the nitric oxide synthase pathway: role of asymmetric dimethylarginine. Circulation 2001; 104, 2569-2575. Go to original source... Go to PubMed...
  65. McGrath C. M., Young S. P. Lipid and Metabolic Changes in Rheumatoid Arthritis. Curr. Rheumatol. Rep. 2015; 17, 57. Go to original source... Go to PubMed...
  66. Erum U., Ahsan T., Khowaja D. Lipid abnormalities in patients with Rheumatoid Arthritis. Pak. J. Med. Sci. 2017; 33, 227-230. Go to original source... Go to PubMed...
  67. Myasoedova E., Crowson C. S., Kremers H. M., Fitz-Gibbon P. D., Therneau T. M., Gabriel S. E. Total cholesterol and LDL levels decrease before rheumatoid arthritis. Ann. Rheum. Dis. 2010; 69, 1310-1314. Go to original source... Go to PubMed...
  68. Nurmohamed M. T. Atherogenic lipid profiles and its management in patients with rheumatoid arthritis. Vasc. Health Risk Manag. 2007; 3, 845-852.
  69. White D., Fayez S., Doube A. Atherogenic lipid profiles in rheumatoid arthritis. N. Z. Med. J. 2006; 119, U2125.
  70. Choy E., Ganeshalingam K., Semb A. G., Szekanecz Z., Nurmohamed M. Cardiovascular risk in rheumatoid arthritis: recent advances in the understanding of the pivotal role of inflammation, risk predictors and the impact of treatment. Rheumatology (Oxford) 2014; 53, 2143-2154. Go to original source... Go to PubMed...
  71. AbouAssi H., Connelly M. A., Bateman L. A., Tune K. N., Huebner J. L., Kraus V. B., Winegar D. A., Otvos J. D., Kraus W. E., Huffman K. M. Does a lack of physical activity explain the rheumatoid arthritis lipid profile? Lipids Health Dis. 2017; 16, 39. Go to original source... Go to PubMed...
  72. Walsmith J., Roubenoff R. Cachexia in rheumatoid arthritis. Int. J. Cardiol. 2002; 85, 89-99. Go to original source... Go to PubMed...
  73. Roubenoff R., Roubenoff R. A., Cannon J. G., Kehayias J. J., Zhuang H., Dawson-Hughes B., Dinarello C. A., Rosenberg I. H. Rheumatoid cachexia: cytokine-driven hypermetabolism accompanying reduced body cell mass in chronic inflammation. J. Clin. Invest. 1994; 93, 2379-2386. Go to original source... Go to PubMed...
  74. Jin X., Yao T., Zhou Z., Zhu J., Zhang S., Hu W., Shen C. Advanced Glycation End Products Enhance Macrophages Polarization into M1 Phenotype through Activating RAGE/NF-κB Pathway. Biomed. Res. Int. 2015; 2015, 732450. Go to original source... Go to PubMed...
  75. Klafke J. Z., Porto F. G., Batista R., Bochi G. V., Moresco R. N., da Luz P. L., Viecili P. R. Association between hypertriglyceridemia and protein oxidation and proinflammatory markers in normocholesterolemic and hypercholesterolemic individuals. Clin. Chim. Acta 2015; 448, 50-57. Go to original source... Go to PubMed...
  76. Charles-Schoeman C., Lee Y. Y., Grijalva V., Amjadi S., FitzGerald J., Ranganath V. K., Taylor M., McMahon M., Paulus H. E., Reddy S. T. Cholesterol efflux by high density lipoproteins is impaired in patients with active rheumatoid arthritis. Ann. Rheum. Dis. 2012; 71, 1157-1162. Go to original source... Go to PubMed...
  77. Tanimoto N., Kumon Y., Suehiro T., Ohkubo S., Ikeda Y., Nishiya K., Hashimoto K. Serum paraoxonase activity decreases in rheumatoid arthritis. Life Sci. 2003; 72, 2877-2885. Go to original source... Go to PubMed...
  78. Başkol M., Başkol G., Deniz K., Ozbakir O., Yücesoy M. A new marker for lipid peroxidation: serum paraoxonase activity in non-alcoholic steatohepatitis. Turk. J. Gastroenterol. 2005; 16, 119-123.
  79. Walker B. R. Glucocorticoids and cardiovascular disease. Eur. J. Endocrinol. 2007; 157, 545-559. Go to original source... Go to PubMed...
  80. Verhoeven F., Prati C., Maguin-Gaté K., Wendling D., Demougeot C. Glucocorticoids and endothelial function in inflammatory diseases: focus on rheumatoid arthritis. Arthritis Res. Ther. 2016; 18, 258. Go to original source... Go to PubMed...
  81. Cooper C., Bardin T., Brandi M. L., Cacoub P., Caminis J., Civitelli R., Cutolo M., Dere W., Devogelaer J. P., Diez-Perez A., Einhorn T. A., Emonts P., Ethgen O., Kanis J. A., Kaufman J. M., Kvien T. K., Lems W. F., McCloskey E., Miossec P., Reiter S., Ringe J., Rizzoli R., Saag K., Reginster J. Y. Balancing benefits and risks of glucocorticoids in rheumatic diseases and other inflammatory joint disorders: new insights from emerging data. An expert consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Aging Clin. Exp. Res. 2016; 28, 1-16. Go to original source... Go to PubMed...
  82. Smolen J. S., Steiner G. Therapeutic strategies for rheumatoid arthritis. Nat. Rev. Drug. Discov. 2003; 2, 473-488. Go to original source... Go to PubMed...
  83. Jacobsson L. T., Turesson C., Gülfe A., Kapetanovic M. C., Petersson I. F., Saxne T., Geborek P. Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis. J. Rheumatol. 2005; 32, 1213-1218.




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