Autoimmune diseases & cardiovascular risk
20th Sep, 2022


According to a recent epidemiological study, individuals with autoimmune disease have a higher risk of developing cardiovascular disease (CVD) than individuals without an autoimmune disease (1). 

Autoimmune diseases are chronic conditions characterised by loss of immune tolerance, aberrant immune responses, and the production of autoantibodies that attack the body's tissues and organs, resulting in inflammation and damage (2). More than 80 autoimmune diseases have been recognised, collectively affecting 5-9% of the global population (1,3). Given that their effects on morbidity and mortality are high, they represent a serious global public health threat. 

Epidemiological studies have found that specific autoimmune diseases are associated with increased cardiovascular morbidity and mortality, including rheumatoid arthritis (4,5), psoriasis (6,7,8), and systemic lupus erythematosus (SLE) (9,10). However, most studies focused on one autoimmune disease entity at a time, had small sample sizes and short duration of follow-up and insufficiently assessed interactions with traditional cardiovascular risk factors, rendering the evidence inconclusive. 


A recent population study of more than 22 million adults in the United Kingdom investigated 19 common autoimmune diseases as potential determinants of future cardiovascular events. The study's results show that patients with autoimmune conditions have an approximately 1.4–3.6 times higher risk of developing CVD than people without an autoimmune disorder, depending on the specific autoimmune disorder. This excess risk is comparable to other well-known cardiovascular risk factors, including type 2 diabetes, hyperlipidaemia, and hypertension. The highest cardiovascular risk was observed in systemic sclerosis, Addison’s disease, SLE, and type 1 diabetes.

The 19 autoimmune diseases investigated in the study accounted for 6.3% of cardiovascular events. Results of sensitivity analysis demonstrated that this excess risk was not attributable to other known cardiovascular risk factors, including age, sex, socioeconomic status, blood pressure, BMI, smoking, type 2 diabetes, or cholesterol. 

Other significant findings were the early age of onset in those with autoimmune disease (< 45 years) and the accelerated course of atherosclerotic diseases, including ischaemic heart disease, peripheral arterial disease, and stroke or transient ischaemic attack. In addition, the risk of inflammatory cardiac disease (pericarditis and myocarditis) and degenerative heart disease (non-rheumatic valve disorders and heart failure) was also increased.


Chronic and systemic inflammation, attributed mainly to the presence of proinflammatory cytokines and autoantibodies, is likely to contribute to the higher observed cardiovascular risk among patients with autoimmune disease (2,11,12,13). In autoimmune disease, a shift toward proinflammatory T helper 1 (Th1) and T helper 17 (Th17) cells and decreased function and number of anti-inflammatory T regulatory (Treg) cells promote an inflammatory environment (14,15,16). This chronic inflammation enhances endothelial dysfunction, induces maladaptive remodelling of the vascular wall, and causes plaque instability and rupture (17,18).

Several other biological mechanisms are proposed to underlie the association between autoimmune disease and CVD. Defects in the complement system or in its regulatory proteins may contribute to the development of autoimmune diseases (19). These defects can also contribute to the development and progression of atherosclerosis by activating endothelial cells, stimulating cytokine release from vascular smooth muscle cells, and promoting plaque rupture (20). Complement activation also influences thrombosis through activation of platelets, promotion of fibrin formation, and impairment of fibrinolysis (21). Autoantibodies against protein antigens, nucleic acids, and lipids can cause endothelial and cardiomyocyte damage, vasculitis, and thrombosis and disrupt lipid homeostasis (22,23,24,25,26,27). 

A key limitation of the current study was the inability to account for the effect of concomitant medication on the association between autoimmune disease and cardiovascular risk. Previous studies have found that medications such as glucocorticoids enhance cardiovascular risk factors. These risk factors include obesity, insulin resistance, glucose intolerance, dyslipidaemia, and hypertension (28,29,30). 



Emerging evidence indicates that autoimmunity and inflammation play a pivotal role in the pathophysiology of CVD. Therefore, the current study highlights that cardiovascular risk prevention should be considered an integral part of managing autoimmune disease. 

Therapies that reduce systemic inflammation, such as polyphenols (e.g. curcumin (31), epigallocatechin gallate (EGCG) (32), and resveratrol (33)) and omega-3 fatty acids (34), may be beneficial. In addition, managing traditional cardiovascular risk factors through a healthy diet, maintaining a healthy weight, exercising, managing stress, and not smoking are essential strategies for preventing and managing cardiovascular risk in autoimmune patients. 

Further research is needed to understand the biological mechanisms linking autoimmune disease and cardiovascular morbidity and to design and assess the effectiveness of CVD prevention measures for patients with autoimmune disorders.

1Conrad N, Verbeke G, Molenberghs G, Goetschalckx L, Callender T, Cambridge G, Mason JC, Rahimi K, McMurray JJ, Verbakel JY. Autoimmune diseases and cardiovascular risk: a population-based study on 19 autoimmune diseases and 12 cardiovascular diseases in 22 million individuals in the UK. The Lancet. 2022 Aug 27.
2Shamriz O, Nussinovitch U, Rose NR. Pathophysiology of Autoimmunity and Immune-Mediated Mechanisms in Cardiovascular Diseases. In The Heart in Rheumatic, Autoimmune and Inflammatory Diseases 2017 Jan 1 (pp. 3-23). Academic Press.
3Lerner A, Jeremias P, Matthias T. The world incidence and prevalence of autoimmune diseases is increasing. Int J Celiac Dis. 2015 Nov 16;3(4):151-5.
4Blum A, Adawi M. Rheumatoid arthritis (RA) and cardiovascular disease. Autoimmunity reviews. 2019 May 3;18(7):679-90.
5Meyer PW, Anderson R, Ker JA, Ally MT. Rheumatoid arthritis and risk of cardiovascular disease. Cardiovascular journal of Africa. 2018 Sep 1;29(5):317-21.
6Jindal S, Jindal N. Psoriasis and cardiovascular diseases: a literature review to determine the causal relationship. Cureus. 2018 Feb 15;10(2).
7Snekvik I, Nilsen TI, Romundstad PR, Saunes M. Psoriasis and cardiovascular disease risk factors: the HUNT Study, Norway. Journal of the European Academy of Dermatology and Venereology. 2018 May;32(5):776-82.
8Egeberg A, Thyssen JP, Jensen P, Gislason GH, Skov L. Risk of Myocardial Infarction in Patients with Psoriasis and Psoriatic Arthritis: A Nationwide Cohort Study. Acta dermato-venereologica. 2017 Jul 1;97(7).
9Kostopoulou M, Nikolopoulos D, Parodis I, Bertsias G. Cardiovascular disease in systemic lupus erythematosus: recent data on epidemiology, risk factors and prevention. Current Vascular Pharmacology. 2020 Nov 1;18(6):549-65.
10Oliveira CB, Kaplan MJ. Cardiovascular disease risk and pathogenesis in systemic lupus erythematosus. In Seminars in Immunopathology 2022 Mar 30 (pp. 1-16). Springer Berlin Heidelberg.
11Mason JC, Libby P. Cardiovascular disease in patients with chronic inflammation: mechanisms underlying premature cardiovascular events in rheumatologic conditions. European heart journal. 2015 Feb 21;36(8):482-9.
12Santos-Moreno P, Burgos-Angulo G, Martinez-Ceballos MA, Pizano A, Echeverri D, Bautista-Niño PK, Roks AJ, Rojas-Villarraga A. Inflammaging as a link between autoimmunity and cardiovascular disease: the case of rheumatoid arthritis. RMD open. 2021 Jan 1;7(1):e001470.
13Durante A, Bronzato S. The increased cardiovascular risk in patients affected by autoimmune diseases: review of the various manifestations. Journal of clinical medicine research. 2015 Jun;7(6):379.
14Leung S, Liu X, Fang L, Chen X, Guo T, Zhang J. The cytokine milieu in the interplay of pathogenic Th1/Th17 cells and regulatory T cells in autoimmune disease. Cellular & molecular immunology. 2010 May;7(3):182-9.
15Albany CJ, Trevelin SC, Giganti G, Lombardi G, Scottà C. Getting to the heart of the matter: the role of regulatory T-cells (Tregs) in cardiovascular disease (CVD) and atherosclerosis. Frontiers in immunology. 2019 Nov 28;10:2795.
16Dominguez-Villar M, Hafler DA. Regulatory T cells in autoimmune disease. Nature immunology. 2018 Jul;19(7):665-73.
17Abou-Raya A, Abou-Raya S. Inflammation: a pivotal link between autoimmune diseases and atherosclerosis. Autoimmunity reviews. 2006 May 1;5(5):331-7.
18Sanjadi M, Rezvanie Sichanie Z, Totonchi H, Karami J, Rezaei R, Aslani S. Atherosclerosis and autoimmunity: a growing relationship. International journal of rheumatic diseases. 2018 May;21(5):908-21.
19Jia C, Tan Y, Zhao M. The complement system and autoimmune diseases. Chronic Diseases and Translational Medicine. 2022.
20Hovland A, Jonasson L, Garred P, Yndestad A, Aukrust P, Lappegård KT, Espevik T, Mollnes TE. The complement system and toll-like receptors as integrated players in the pathophysiology of atherosclerosis. Atherosclerosis. 2015 Aug 1;241(2):480-94.
21Luo S, Hu D, Wang M, Zipfel PF, Hu Y. Complement in hemolysis-and thrombosis-related diseases. Frontiers in immunology. 2020 Jul 10;11:1212.
22Foteinos G, Xu Q. Immune-mediated mechanisms of endothelial damage in atherosclerosis. Autoimmunity. 2009 Jan 1;42(7):627-33.
23Kaya Z, Leib C, Katus HA. Autoantibodies in heart failure and cardiac dysfunction. Circulation research. 2012 Jan 6;110(1):145-58.
24Afanasyeva M, Georgakopoulos D, Rose NR. Autoimmune myocarditis: cellular mediators of cardiac dysfunction. Autoimmunity reviews. 2004 Nov 1;3(7-8):476-86.
25Ye Y, Wu T, Zhang T, Han J, Habazi D, Saxena R, Mohan C. Elevated oxidized lipids, anti-lipid autoantibodies and oxidized lipid immune complexes in active SLE. Clinical Immunology. 2019 Aug 1;205:43-8.
26Freyssinet JM, Ravanat C, Grunebaum L, Wiesel ML, Cazenave JP. Anti-phospholipid autoantibodies in thrombosis: cause and/or consequence of the disruption of the protein C-dependent hemostatic balance. InPhospholipid-Binding Antibodies 2020 Apr 15 (pp. 255-267). CRC Press.
27Lamprecht P, Kerstein A, Klapa S, Schinke S, Karsten CM, Yu X, Ehlers M, Epplen JT, Holl-Ulrich K, Wiech T, Kalies K. Pathogenetic and clinical aspects of anti-neutrophil cytoplasmic autoantibody-associated vasculitides. Frontiers in immunology. 2018 Apr 9;9:680.
28Walker BR. Glucocorticoids and cardiovascular disease. European journal of endocrinology. 2007 Nov 1;157(5):545-59.
29Del Rincón I, Battafarano DF, Restrepo JF, Erikson JM, Escalante A. Glucocorticoid dose thresholds associated with all‐cause and cardiovascular mortality in rheumatoid arthritis. Arthritis & rheumatology. 2014 Feb;66(2):264-72.
30Roubille C, Richer V, Starnino T, McCourt C, McFarlane A, Fleming P, Siu S, Kraft J, Lynde C, Pope J, Gulliver W. The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Annals of the rheumatic diseases. 2015 Mar 1;74(3):480-9.
31Yang M, Akbar U, Mohan C. Curcumin in autoimmune and rheumatic diseases. Nutrients. 2019 May 2;11(5):1004.
32Wu D, Wang J, Pae M, Meydani SN. Green tea EGCG, T cells, and T cell-mediated autoimmune diseases. Molecular aspects of medicine. 2012 Feb 1;33(1):107-18.
33Oliveira AL, Monteiro VV, Navegantes-Lima KC, Reis JF, Gomes RD, Rodrigues DV, Gaspar SL, Monteiro MC. Resveratrol role in autoimmune disease—a mini-review. Nutrients. 2017 Dec 1;9(12):1306.
34Duarte-Garcia A, Myasoedova E, Karmacharya P, Hocaoğlu M, Murad MH, Warrington KJ, Crowson CS. Effect of omega-3 fatty acids on systemic lupus erythematosus disease activity: A systematic review and meta-analysis. Autoimmunity Reviews. 2020 Dec 1;19(12):102688.