Atherosclerosis in autoimmune rheumatic diseases

Autoimmune rheumatic and musculoskeletal diseases (RMDs) including rheumatoid arthritis (RA) and systemic sclerosis (SSc) and others have been associated with increased cardiovascular (CV) risk, morbidity and mortality [ 1 Agca R. Heslinga S.C. Rollefstad S. Heslinga M. McInnes I.B. Peters M.J. et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis. 2017; 76: 17-28 Crossref PubMed Scopus (780) Google Scholar , 2 Drosos G.C. Vedder D. Houben E. Boekel L. Atzeni F. Badreh S. et al. EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome. Ann Rheum Dis. 2022; 81: 768-779 Crossref PubMed Scopus (46) Google Scholar , 3 Shoenfeld Y. Gerli R. Doria A. Matsuura E. Cerinic M.M. Ronda N. et al. Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation. 2005; 112: 3337-3347 Crossref PubMed Scopus (480) Google Scholar , 4 Timar O. Szekanecz Z. Kerekes G. Vegh J. Olah A.V. Nagy G. et al. Rosuvastatin improves impaired endothelial function, lowers high sensitivity CRP, complement and immuncomplex production in patients with systemic sclerosis–a prospective case-series study. Arthritis Res Ther. 2013; 15: R105 Crossref PubMed Scopus (34) Google Scholar , 5 Szekanecz Z. Kerekes G. Vegh E. Kardos Z. Barath Z. Tamasi L. et al. Autoimmune atherosclerosis in 3D: how it develops, how to diagnose and what to do. Autoimmun Rev. 2016; 15: 756-769 Crossref PubMed Scopus (40) Google Scholar ]. Both traditional and inflammatory risk factors have been implicated in the development of accelerated atherosclerosis and vascular pathologies in these conditions [ 1 Agca R. Heslinga S.C. Rollefstad S. Heslinga M. McInnes I.B. Peters M.J. et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis. 2017; 76: 17-28 Crossref PubMed Scopus (780) Google Scholar , 2 Drosos G.C. Vedder D. Houben E. Boekel L. Atzeni F. Badreh S. et al. EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome. Ann Rheum Dis. 2022; 81: 768-779 Crossref PubMed Scopus (46) Google Scholar , 3 Shoenfeld Y. Gerli R. Doria A. Matsuura E. Cerinic M.M. Ronda N. et al. Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation. 2005; 112: 3337-3347 Crossref PubMed Scopus (480) Google Scholar , [5] Szekanecz Z. Kerekes G. Vegh E. Kardos Z. Barath Z. Tamasi L. et al. Autoimmune atherosclerosis in 3D: how it develops, how to diagnose and what to do. Autoimmun Rev. 2016; 15: 756-769 Crossref PubMed Scopus (40) Google Scholar , [6] Sherer Y. Shoenfeld Y. Mechanisms of disease: atherosclerosis in autoimmune diseases. Nat Clin Pract Rheumatol. 2006; 2: 99-106 Crossref PubMed Scopus (305) Google Scholar ]. Systemic inflammation, disease activity and flares are major drivers of subclinical and then clinical atherosclerosis, acute coronary syndrome (ACS) and overt CV disease (CVD) [ 1 Agca R. Heslinga S.C. Rollefstad S. Heslinga M. McInnes I.B. Peters M.J. et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis. 2017; 76: 17-28 Crossref PubMed Scopus (780) Google Scholar , 2 Drosos G.C. Vedder D. Houben E. Boekel L. Atzeni F. Badreh S. et al. EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome. Ann Rheum Dis. 2022; 81: 768-779 Crossref PubMed Scopus (46) Google Scholar , 3 Shoenfeld Y. Gerli R. Doria A. Matsuura E. Cerinic M.M. Ronda N. et al. Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation. 2005; 112: 3337-3347 Crossref PubMed Scopus (480) Google Scholar , [5] Szekanecz Z. Kerekes G. Vegh E. Kardos Z. Barath Z. Tamasi L. et al. Autoimmune atherosclerosis in 3D: how it develops, how to diagnose and what to do. Autoimmun Rev. 2016; 15: 756-769 Crossref PubMed Scopus (40) Google Scholar , [7] Ljung L. Simard J.F. Jacobsson L. Rantapaa-Dahlqvist S. Askling J. Anti-Rheumatic Therapy in Sweden Study G. Treatment with tumor necrosis factor inhibitors and the risk of acute coronary syndromes in early rheumatoid arthritis. Arthritis Rheum. 2012; 64: 42-52 Crossref PubMed Scopus (59) Google Scholar , [8] Myasoedova E. Chandran A. Ilhan B. Major B.T. Michet C.J. Matteson E.L. et al. The role of rheumatoid arthritis (RA) flare and cumulative burden of RA severity in the risk of cardiovascular disease. Ann Rheum Dis. 2016; 75: 560-565 Crossref PubMed Scopus (122) Google Scholar ]. Non-invasive ultrasound- or computed tomography (CT)-based techniques are suitable for the detection of preclinical endothelial dysfunction, atherosclerosis, and the future risk of CVD [ [1] Agca R. Heslinga S.C. Rollefstad S. Heslinga M. McInnes I.B. Peters M.J. et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis. 2017; 76: 17-28 Crossref PubMed Scopus (780) Google Scholar , [4] Timar O. Szekanecz Z. Kerekes G. Vegh J. Olah A.V. Nagy G. et al. Rosuvastatin improves impaired endothelial function, lowers high sensitivity CRP, complement and immuncomplex production in patients with systemic sclerosis–a prospective case-series study. Arthritis Res Ther. 2013; 15: R105 Crossref PubMed Scopus (34) Google Scholar , 9 Kerekes G. Soltesz P. Nurmohamed M.T. Gonzalez-Gay M.A. Turiel M. Vegh E. et al. Validated methods for assessment of subclinical atherosclerosis in rheumatology. Nat Rev Rheumatol. 2012; 8: 224-234 Crossref PubMed Scopus (111) Google Scholar , 10 Gonzalez-Gay M.A. Gonzalez-Juanatey C. Vazquez-Rodriguez T.R. Martin J. Llorca J. Endothelial dysfunction, carotid intima-media thickness, and accelerated atherosclerosis in rheumatoid arthritis. Semin Arthritis Rheum. 2008; 38: 67-70 Crossref PubMed Scopus (97) Google Scholar , 11 Szucs G. Timar O. Szekanecz Z. Der H. Kerekes G. Szamosi S. et al. Endothelial dysfunction precedes atherosclerosis in systemic sclerosis–relevance for prevention of vascular complications. Rheumatology (Oxford). 2007; 46: 759-762 Crossref PubMed Scopus (110) Google Scholar , 12 Timar O. Soltesz P. Szamosi S. Der H. Szanto S. Szekanecz Z. et al. Increased arterial stiffness as the marker of vascular involvement in systemic sclerosis. J Rheumatol. 2008; 35: 1329-1333 PubMed Google Scholar ]. Targeted therapies that dampen inflammation and disease activity, as well as traditional vasculoprotection including aspirin and statins can minimize CV risk in autoimmune RMDs [ [1] Agca R. Heslinga S.C. Rollefstad S. Heslinga M. McInnes I.B. Peters M.J. et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis. 2017; 76: 17-28 Crossref PubMed Scopus (780) Google Scholar , [2] Drosos G.C. Vedder D. Houben E. Boekel L. Atzeni F. Badreh S. et al. EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome. Ann Rheum Dis. 2022; 81: 768-779 Crossref PubMed Scopus (46) Google Scholar , [4] Timar O. Szekanecz Z. Kerekes G. Vegh J. Olah A.V. Nagy G. et al. Rosuvastatin improves impaired endothelial function, lowers high sensitivity CRP, complement and immuncomplex production in patients with systemic sclerosis–a prospective case-series study. Arthritis Res Ther. 2013; 15: R105 Crossref PubMed Scopus (34) Google Scholar , [7] Ljung L. Simard J.F. Jacobsson L. Rantapaa-Dahlqvist S. Askling J. Anti-Rheumatic Therapy in Sweden Study G. Treatment with tumor necrosis factor inhibitors and the risk of acute coronary syndromes in early rheumatoid arthritis. Arthritis Rheum. 2012; 64: 42-52 Crossref PubMed Scopus (59) Google Scholar , [13] Szekanecz Z. Kerekes G. Soltesz P. Vascular effects of biologic agents in RA and spondyloarthropathies. Nat Rev Rheumatol. 2009; 5: 677-684 Crossref PubMed Scopus (74) Google Scholar ]. The European Alliance of Associations for Rheumatology (EULAR) issued recommendations for the detection, management, and prevention of CVD in RA, SSc, as well as other RMDs [ [1] Agca R. Heslinga S.C. Rollefstad S. Heslinga M. McInnes I.B. Peters M.J. et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis. 2017; 76: 17-28 Crossref PubMed Scopus (780) Google Scholar , [2] Drosos G.C. Vedder D. Houben E. Boekel L. Atzeni F. Badreh S. et al. EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome. Ann Rheum Dis. 2022; 81: 768-779 Crossref PubMed Scopus (46) Google Scholar ].