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Do individuals with autoimmune disease have increased risk of subclinical carotid atherosclerosis and stiffness?

A Correction to this article was published on 30 April 2021

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Abstract

To explore the role of chronic inflammation inherent to autoimmune diseases in the development of subclinical atherosclerosis and arterial stiffness, this study recruited two population-based samples of individuals with and without autoimmune disease (ratio 1:5) matched by age, sex, and education level and with a longstanding (≥6 years) diagnosis of autoimmune disease. Common carotid intima-media thickness (IMT) and arterial distensibility and compliance were assessed with carotid ultrasound. Multivariable linear and logistic regression models were adjusted for 10-year cardiovascular risk. In total, 546 individuals with and without autoimmune diseases (91 and 455, respectively) were included. The mean age was 66 years (standard deviation 12), and 240 (43.9%) were women. Arterial stiffness did not differ according to the presence of autoimmune diseases. In men, the diagnosis of autoimmune diseases significantly increased common carotid IMT [beta-coefficient (95% confidence interval): 0.058 (0.009; 0.108); p value = 0.022] and the percentage with IMT ≥ 75th percentile [1.012 (0.145; 1.880); p value = 0.022]. Women without autoimmune disease were more likely to have IMT ≥ the 75th percentile [−2.181 (−4.214; −0.149); p value = 0.035], but the analysis of IMT as a continuous variable did not yield significant results. In conclusion, subclinical carotid atherosclerosis, but not arterial stiffness, was more common in men with autoimmune diseases. Women did not show significant differences in any of these carotid features. Sex was an effect modifier in the association between common carotid IMT values and the diagnosis of autoimmune diseases.

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References

  1. 1.

    World Health Statistics. Monograph on the internet. Geneva: World Health Organization; 2011. https://www.who.int/data/gho/data/themes/topics/noncommunicable-diseases.

  2. 2.

    Cavalcante JL, Lima JA, Redheuil A, Al-Mallah MH. Aortic stiffness: current understanding and future directions. J Am Coll Cardiol. 2011;57:1511–22. https://doi.org/10.1016/j.jacc.2010.12.017.

    Article  PubMed  Google Scholar 

  3. 3.

    Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N. Engl J Med. 2005;352:1685–1695. https://doi.org/10.1056/NEJMra043430.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Baena-Díez JM, Garcia-Gil M, Comas-Cufí M, Ramos R, Prieto-Alhambra D, Salvador-González B, et al. Association between chronic immune-mediated inflammatory diseases and cardiovascular risk. Heart. 2018;104:119–126. https://doi.org/10.1136/heartjnl-2017-311279.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Dalbeni A, Giollo A, Bevilacqua M, Cioffi G, Tagetti A, Cattazzo F, et al. Traditional cardiovascular risk factors and residual disease activity are associated with atherosclerosis progression in rheumatoid arthritis patients. Hypertens Res. 2020;43:922–8. https://doi.org/10.1038/s41440-020-0441-1.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Jain S, Khera R, Corrales-Medina VF, Townsend RR, Chirinos JA. Inflammation and arterial stiffness in humans. Atherosclerosis. 2014;237:381–90.

    CAS  Article  Google Scholar 

  7. 7.

    Zanoli L, Briet M, Empana JP, Cunha PG, Mäki-Petäjä KM, Protogerou AD, et al. Vascular consequences of inflammation: a position statement from the ESH Working Group on Vascular Structure and Function and the ARTERY Society. J Hypertens. 2020;38:1682–98. https://doi.org/10.1097/HJH.0000000000002508.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Agüero F, González-Zobl G, Baena-Díez JM, Dégano IR, Garcia-Gil M, Alzamora MT, et al. Prevalence of lower extremity peripheral arterial disease in individuals with chronic immune mediated inflammatory disorders. Atherosclerosis. 2015;242:1–7. https://doi.org/10.1016/j.atherosclerosis.2015.06.054.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Grau M, Subirana I, Agis D, Ramos R, Basagaña X, Martí R, et al. Carotid intima-media thickness in the Spanish population: reference ranges and association with cardiovascular risk factors. Rev Esp Cardiol. 2012;65:1086–1093. https://doi.org/10.1016/j.recesp.2012.04.026.

    Article  PubMed  Google Scholar 

  10. 10.

    Martí-Lluch R, Garcia-Gil MDM, Camós L, Comas-Cufí M, Elosua-Bayés M, Blanch J, et al. Differences in cardio-ankle vascular index in a general Mediterranean population depending on the presence or absence of metabolic cardiovascular risk factors. Atherosclerosis. 2017;264:29–35. https://doi.org/10.1016/j.atherosclerosis.2017.07.013.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Grau M, Subirana I, Elosua R, Solanas P, Ramos R, Masiá R, et al. Trends in cardiovascular risk factor prevalence (1995-2000-2005) in northeastern Spain. Eur J Cardiovasc Prev Rehabil. 2007;14:653–659. https://doi.org/10.1097/HJR.0b013e3281764429.

    Article  PubMed  Google Scholar 

  12. 12.

    Bolíbar B, Fina Avilés F, Morros R, Garcia-Gil Mdel M, Hermosilla E, Ramos R, et al. SIDIAP database: electronic clinical records in primary care as a source of information for epidemiologic research. Med Clin. 2012;138:617–621. https://doi.org/10.1016/j.medcli.2012.01.020.

    Article  Google Scholar 

  13. 13.

    Marrugat J, Subirana I, Comín E, Cabezas C, Vila J, Elosua R, et al. Validity of an adaptation of the Framingham cardiovascular risk function: the VERIFICA Study. J Epidemiol Community Health. 2007;61:40–47. https://doi.org/10.1136/jech.2005.038505.

    Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    de Groot E, van Leuven SI, Duivenvoorden R, Meuwese MC, Akdim F, Bots ML, et al. Measurement of carotid intima-media thickness to assess progression and regression of atherosclerosis. Nat Clin Pr Cardiovasc Med. 2008;5:280–288. https://doi.org/10.1038/ncpcardio1163.

    Article  Google Scholar 

  15. 15.

    Vila MDM, Remeseiro B, Grau M, Elosua R, Betriu À, Fernandez-Giraldez E, et al. Semantic segmentation with DenseNets for carotid artery ultrasound plaque segmentation and CIMT estimation. Artif Intell Med. 2020;103:101784. https://doi.org/10.1016/j.artmed.2019.101784.

    Article  PubMed  Google Scholar 

  16. 16.

    Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Bornstein N, et al. Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011. Cerebrovasc Dis. 2012;34:290–296. https://doi.org/10.1159/000343145.

    Article  PubMed  Google Scholar 

  17. 17.

    Van Bortel LM, Duprez D, Starmans-Kool MJ, Safar ME, Giannattasio C, Cockcroft J, et al. Clinical applications of arterial stiffness, Task Force III: recommendations for user procedures. Am J Hypertens. 2002;15:445–52. https://doi.org/10.1016/s0895-7061(01)02326-3.

    Article  PubMed  Google Scholar 

  18. 18.

    Łoboz-Rudnicka M, Jaroch J, Bociąga Z, Rzyczkowska B, Uchmanowicz I, Polański J, et al. Impact of cardiovascular risk factors on carotid intima-media thickness: sex differences. Clin Inter Aging. 2016;11:721–31. https://doi.org/10.2147/CIA.S103521.

    Article  Google Scholar 

  19. 19.

    DuPont JJ, Kenney RM, Patel AR, Jaffe IZ. Sex differences in mechanisms of arterial stiffness. Br J Pharm. 2019;176:4208–25. https://doi.org/10.1111/bph.14624.

    CAS  Article  Google Scholar 

  20. 20.

    Wang P, Guan SY, Xu SZ, Li HM, Leng RX, Li XP, et al. Increased carotid intima-media thickness in rheumatoid arthritis: an update meta-analysis. Clin Rheumatol. 2016;35:315–23. https://doi.org/10.1007/s10067-015-3130-8.

    Article  PubMed  Google Scholar 

  21. 21.

    Henrot P, Foret J, Barnetche T, Lazaro E, Duffau P, Seneschal J, et al. Assessment of subclinical atherosclerosis in systemic lupus erythematosus: a systematic review and meta-analysis. Jt Bone Spine. 2018;85:155–63. https://doi.org/10.1016/j.jbspin.2017.12.009.

    Article  Google Scholar 

  22. 22.

    Wu GC, Leng RX, Lu Q, Fan YG, Wang DG, Ye DQ. Subclinical atherosclerosis in patients with inflammatory bowel diseases: a systematic review and meta-analysis. Angiology. 2017;68:447–61. https://doi.org/10.1177/0003319716652031.

    Article  PubMed  Google Scholar 

  23. 23.

    Bai R, Zhang Y, Liu W, Ma C, Chen X, Yang J, et al. The relationship of ankylosing spondylitis and subclinical atherosclerosis: a systemic review and meta-analysis. Angiology. 2019;70:492–500. https://doi.org/10.1177/0003319718814309.

    Article  PubMed  Google Scholar 

  24. 24.

    Balogh E, Pusztai A, Hamar A, Végh E, Szamosi S, Kerekes G, et al. Autoimmune and angiogenic biomarkers in autoimmune atherosclerosis. Clin Immunol. 2019;199:47–51. https://doi.org/10.1016/j.clim.2018.12.011.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Szekanecz Z, Kerekes G, Végh E, Kardos Z, Baráth Z, Tamási L, et al. Autoimmune atherosclerosis in 3D: how it develops, how to diagnose and what to do. Autoimmun Rev. 2016;15:756–69. https://doi.org/10.1016/j.autrev.2016.03.014.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Agca R, Heslinga SC, Rollefstad S, Heslinga M, McInnes IB, Peters MJ, 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. https://doi.org/10.1136/annrheumdis-2016-209775.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Mosca M, Tani C, Aringer M, Bombardieri S, Boumpas D, Brey R, et al. European League Against Rheumatism recommendations for monitoring patients with systemic lupus erythematosus in clinical practice and in observational studies. Ann Rheum Dis. 2010;69:1269–74. https://doi.org/10.1136/ard.2009.117200.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Coll B, Betriu A, Feinstein SB, Valdivielso JM, Zamorano JL, Fernández E. The role of carotid ultrasound in assessing carotid atherosclerosis in individuals at low-to-intermediate cardiovascular risk. Rev Esp Cardiol. 2013;66:929–34. https://doi.org/10.1016/j.rec.2013.05.030.

    Article  PubMed  Google Scholar 

  29. 29.

    Wu TW, Hung CL, Liu CC, Wu YJ, Wang LY, Yeh HI. Associations of cardiovascular risk factors with carotid intima-media thickness in middle-age adults and elders. J Atheroscler Thromb. 2017;24:677–86. https://doi.org/10.5551/jat.37895.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Frerix M, Stegbauer J, Kreuter A, Weiner SM. Atherosclerotic plaques occur in absence of intima-media thickening in both systemic sclerosis and systemic lupus erythematosus: a duplexsonography study of carotid and femoral arteries and follow-up for cardiovascular events. Arthritis Res Ther. 2014;16:R54. https://doi.org/10.1186/ar4489.

    Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Kurmann RD, Mankad R. Atherosclerotic heart disease in women with autoimmune rheumatologic inflammatory conditions. Can J Cardiol. 2018;34:381–9. https://doi.org/10.1016/j.cjca.2018.01.015.

    Article  PubMed  Google Scholar 

  32. 32.

    Mendoza-Pinto C, Rojas-Villarraga A, Molano-González N, García-Carrasco M, Munguía-Realpozo P, Etchegaray-Morales I, et al. Endothelial dysfunction and arterial stiffness in patients with systemic lupus erythematosus: a systematic review and meta-analysis. Atherosclerosis. 2020;297:55–63. https://doi.org/10.1016/j.atherosclerosis.2020.01.028.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Ambrosino P, Tasso M, Lupoli R, Di Minno A, Baldassarre D, Tremoli E, et al. Non-invasive assessment of arterial stiffness in patients with rheumatoid arthritis: a systematic review and meta-analysis of literature studies. Ann Med. 2015;47:457–67. https://doi.org/10.3109/07853890.2015.1068950.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Wang P, Huang L, Xu Q, Xu L, Deng FY, Lei SF. Assessment of aortic stiffness in patients with rheumatoid arthritis using pulse wave velocity: an update meta-analysis. Arch Med Res. 2019;50:401–12. https://doi.org/10.1016/j.arcmed.2019.10.010.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Teixeira R, Vieira MJ, Gonçalves A, Cardim N, Gonçalves L. Ultrasonographic vascular mechanics to assess arterial stiffness: a review. Eur Heart J Cardiovasc Imaging. 2016;17:233–46. https://doi.org/10.1093/ehjci/jev287.

    Article  PubMed  Google Scholar 

  36. 36.

    Katakami N, Mita T, Gosho M, Takahara M, Irie Y, Yasuda T, et al. Clinical utility of carotid ultrasonography in the prediction of cardiovascular events in patients with diabetes: a combined analysis of data obtained in five longitudinal studies. J Atheroscler Thromb. 2018;25:1053–1066.

    CAS  Article  Google Scholar 

  37. 37.

    Kokubo Y, Watanabe M, Higashiyama A, Nakao YM, Nakamura F, Miyamoto Y. Impact of intima-media thickness progression in the common carotid arteries on the risk of incident cardiovascular disease in the Suita study. J Am Heart Assoc. 2018;7:e007720. https://doi.org/10.1161/JAHA.117.007720.

    Article  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Polak JF, O’Leary DH. Carotid intima-media thickness as surrogate for and predictor of CVD. Glob Heart 2016;11:295–312.e3. https://doi.org/10.1016/j.gheart.2016.08.006.

    Article  PubMed  Google Scholar 

  39. 39.

    Vila MDM, Remeseiro B, Grau M, Elosua R, Betriu À, Fernandez-Giraldez E, et al. Semantic segmentation with DenseNets for carotid artery ultrasound plaque segmentation and CIMT estimation. Artif Intell Med. 2020;103:101784. https://doi.org/10.1016/j.artmed.2019.101784.

    Article  PubMed  Google Scholar 

  40. 40.

    Nagy G, Németh N, Buzás EI. Mechanisms of vascular comorbidity in autoimmune diseases. Curr Opin Rheumatol. 2018;30:197–206. https://doi.org/10.1097/BOR.0000000000000483.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Ramos R, Balló E, Marrugat J, Elosua R, Sala J, Grau M, et al. Validity for use in research on vascular diseases of the SIDIAP (Information System for the Development of Research in Primary Care): the EMMA study. Rev Esp Cardiol. 2012;65:29–37. https://doi.org/10.1016/j.recesp.2011.07.017.

    Article  PubMed  Google Scholar 

  42. 42.

    Fina-Aviles F, Medina-Peralta M, Mendez-Boo L, Hermosilla E, Elorza JM, Garcia-Gil M, et al. The descriptive epidemiology of rheumatoid arthritis in Catalonia: a retrospective study using routinely collected data. Clin Rheumatol. 2016;35:751–757. https://doi.org/10.1007/s10067-014-2801-1.

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Carmona L, Villaverde V, Hernández-García C, Ballina J, Gabriel R, Laffon A. EPISER Study Group. The prevalence of rheumatoid arthritis in the general population of Spain. Rheumatology. 2002;41:88–95. https://doi.org/10.1093/rheumatology/41.1.88.

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    López P, Mozo L, Gutiérrez C, Suárez A. Epidemiology of systemic lupus erythematosus in a northern Spanish population: gender and age influence on immunological features. Lupus. 2003;12:860–865. https://doi.org/10.1191/0961203303lu469xx.

    Article  PubMed  Google Scholar 

  45. 45.

    Saro Gismera C, Riestra Menéndez S, Sánchez Fernández R, Milla Crespo A, Lacort Fernández M, Argüelles Fernández G, et al. Epidemiology in inflammatory bowel disease in five areas of Asturias. Spain. Med Interna. 2003;20:232–238.

    CAS  Google Scholar 

  46. 46.

    Sarabi M, Lind L. Short-term effects of smoking and nicotine chewing gum on endothelium-dependent vasodilation in young healthy habitual smokers. J Cardiovasc Pharm. 2000;35:451–6. https://doi.org/10.1097/00005344-200003000-00016.

    CAS  Article  Google Scholar 

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Acknowledgements

The authors appreciate the System for the Development of Research in Primary Care (SIDIAP) database access, the expert review on autoimmune diseases by Dr. Albert Escola Campabadal, and revision of the English text by Elaine Lilly PhD.

Funding

Supported by grants from the Instituto de Salud Carlos III FEDER (CP12/03287, CP17/00012), Health Research Fund (FIS 2003/HERMES PI20471, PI070403, ETES: PI07/90415, FIS11/06765) and Principado de Asturias Regional Government (IDI-2018–000176). Partially supported with European Regional Development Fund funds and grants from Spain’s Ministerio de Ciencia, Innovación y Universidades (RTI2018–095232-B-C21) and the Generalitat de Catalunya (2017 SGR 1742).

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Correspondence to Maria Grau.

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Vila, M.d.M., Remeseiro, B., Igual, L. et al. Do individuals with autoimmune disease have increased risk of subclinical carotid atherosclerosis and stiffness?. Hypertens Res 44, 978–987 (2021). https://doi.org/10.1038/s41440-021-00655-9

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Keywords

  • Atherosclerosis
  • Autoimmune Diseases
  • Cardiovascular Diseases
  • Carotid Intima-Media Thickness

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