Characteristics of atherosclerotic plaque and the thickness of the carotid artery intima-media complex in patients with rheumatoid arthritis
Abstract
Background/Aim. Rheumatoid arthritis (RA) represents an independent risk factor for the development of cardio-vascular (CV) disease (CVD). Early detection of atheroscle-rotic changes is of tremendous importance in the preven-tion of CV events. An increase in the carotid artery intima-media thickness (cIMT) is considered a sensitive marker of early subclinical atherosclerosis. The aim of our investiga-tion was to assess the cIMT, the number and type of carotid plaques (CPs), and the severity of carotid artery stenosis in RA patients. Furthermore, we investigated the correlation between all the above-mentioned parameters and disease duration and activity. Methods. The research included 92 participants, of which 58 were patients with RA, and the remaining 34 participants were healthy individuals (control group). In patients with RA, clinical examination and labor-atory findings were used for assessing disease activity. All participants underwent a color Doppler ultrasound exami-nation of the carotid arteries with a linear probe in order to assess cIMT, the number and type of CPs, as well as the se-verity of stenotic lesions. Results. The mean cIMT in RA patients was statistically significantly higher compared to the control group (0.8 ± 0.2 mm vs. 0.7 ± 0.2 mm; p < 0.01). CPs were found in 34 out of 58 RA patients (58.6%) and 4 out of 34 (11.8%) participants in the control group (p < 0.001). The number of CPs per patient was signifi-cantly higher in the RA group compared to the control group (1.4 ± 0.9 vs. 0.2 ± 0.4; p < 0.001). The cIMT, the presence and number of CPs, and the severity of carotid artery stenosis were not statistically significantly related to disease activity. There was a statistically significant direct correlation between the duration of RA and the percent-age of carotid arterial stenosis (r = 0.320, p = 0.034). Con-clusion. The cIMT and the presence and number of CPs per patient were significantly higher in RA patients. More-over, there was a positive correlation between RA disease duration and the severity of carotid artery stenosis. This study showed that RA represents an independent risk fac-tor for an increase in cIMT and the development of sub-clinical atherosclerosis.
References
1. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011 Dec 8; 365(23): 2205–19.
2. Gonzalez-Gay MA, Gonzalez-Juanatey C, Martin J. Rheumatoid arthritis: a disease associated with accelerated atherogenesis. Semin Arthritis Rheum 2005; 35(1): 8‒17.
3. Sattar N, McCarey DW, Capell H, McInnes IB. Explaining how "high-grade" systemic inflammation accelerates vascu-lar risk in rheumatoid arthritis. Circulation 2003; 108(24): 2957‒63.
4. Choy EH, Panayi GS. Cytokine pathways and joint inflamma-tion in rheumatoid arthritis. N Engl J Med 2001; 344(12): 907‒16.
5. Gonzalez-Gay MA, Gonzalez-Juanatey C, Martin J. Inflammation and endothelial dysfunction in rheumatoid arthritis. Clin Exp Rheumatol 2006; 24: 115–7.
6. Bartoloni E, Alunno A, Bistoni O, Gerli R. How early is the ath-erosclerotic risk in rheumatoid arthritis? Autoimmun Rev 2010; 9(10): 701–7.
7. Gauri LA, Fatima Q, Diggi S, Khan A, Liyakat A, Nagar K. Study of Carotid Artery Intimomedial Thickness in Pa-tients with Rheumatoid Arthritis and its Co-relation with Severity of the Disease. J Assoc Physicians India 2017; 65(7): 37‒40.
8. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010; 62(9): 2569‒81.
9. Aletaha D, Smolen JS. The Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) to monitor patients in standard clinical care. Best Pract Res Clin Rheu-matol 2007; 21(4): 663‒75.
10. Fransen J, van Riel PL. The Disease Activity Score and the EU-LAR response criteria. Rheum Dis Clin North Am 2009; 35(4): 745‒57, vii-viii.
11. Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Desvarieux M, et al. Advisory Board of the 3rd Watching the Risk Symposium 2004, 13th European Stroke Conference. Mannheim intima-media thickness consensus. Cerebrovasc Dis 2004; 18(4): 346‒9.
12. Park TH. Evaluation of Carotid Plaque Using Ultrasound Im-aging. J Cardiovasc Ultrasound. 2016; 24(2): 91‒5.
13. National Institute of Neurological Disorders and Stroke Stroke and Trauma Division. North American Symptomatic Carotid Endarterectomy Trial (NASCET) investigators. Clinical alert: benefit of carotid endarterectomy for patients with high-grade stenosis of the internal carotid artery. Stroke 1991; 22(6): 816‒7.
14. Grant EG, Benson CB, Moneta GL, Alexandrov AV, Baker JD, Bluth EI, et al. Carotid artery stenosis: gray-scale and Doppler US diagnosis-society of radiologists in ultrasound consensus conference. Radiology 2003; 229(2): 340‒6.
15. Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, et al. ESC Scientific Document Group. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardio-vascular Prevention & Rehabilitation (EACPR). Eur Heart J 2016; 37(29): 2315‒81.
16. Urman A, Taklalsingh N, Sorrento C, McFarlane IM. Inflamma-tion beyond the Joints: Rheumatoid Arthritis and Cardiovascu-lar Disease. Scifed J Cardiol 2018; 2(3): 1000019.
17. Grover S, Sinha RP, Singh U, Tewari S, Aggarwal A, Misra R. Sub-clinical atherosclerosis in rheumatoid arthritis in India. J Rheumatol 2006; 33(2): 244‒7.
18. Zou K, Xiao FK, Li HY, Zhou Q, Ban L, Yang M, et al. Risk of cardiovascular disease in Chinese patients with rheumatoid ar-thritis: A cross-sectional study based on hospital medical rec-ords in 10 years. PLoS One 2017; 12(7): e0180376.
19. van Halm VP, Peters MJ, Voskuyl AE, Boers M, Lems WF, Visser M, et al. Rheumatoid arthritis versus diabetes as a risk factor for cardiovascular disease: a cross-sectional study, the CARRE Investigation. Ann Rheum Dis 2009; 68(9): 1395‒400.
20. Lassere MN, Rappo J, Portek IJ, Sturgess A, Edmonds JP. How many life years are lost in patients with rheumatoid arthritis? Secular cause-specific and all-cause mortality in rheumatoid ar-thritis, and their predictors in a long-term Australian cohort study. Intern Med J 2013; 43(1): 66‒72.
21. van den Hoek J, Boshuizen HC, Roorda LD, Tijhuis GJ, Nurmo-hamed MT, van den Bos GA, et al. Mortality in patients with rheumatoid arthritis: a 15-year prospective cohort study. Rheumatol Int 2017; 37(4): 487‒93.
22. Crowson CS, Nicola PJ, Kremers HM, O'Fallon WM, Therneau TM, Jacobsen SJ, et al. How much of the increased incidence of heart failure in rheumatoid arthritis is attributable to traditional car-diovascular risk factors and ischemic heart disease? Arthritis Rheum 2005; 52(10): 3039‒44.
23. GBD 2017 Causes of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analy-sis for the Global Burden of Disease Study 2017. Lancet 2018; 392(10159): 1736‒88.
24. Maradit-Kremers H, Crowson CS, Nicola PJ, Ballman KV, Roger VL, Jacobsen SJ, et al. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a popula-tion-based cohort study. Arthritis Rheum 2005; 52(2): 402‒11.
25. Aviña-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum 2008; 59(12): 1690–7.
26. de Groot E, Hovingh GK, Wiegman A, Duriez P, Smit AJ, Fruchart JC, et al. Measurement of arterial wall thickness as a surrogate marker for atherosclerosis. Circulation 2004; 109(23 Suppl 1): III33‒8.
27. Park YB, Ahn CW, Choi HK, Lee SH, In BH, Lee HC, et al. Atherosclerosis in rheumatoid arthritis: morphologic evidence obtained by carotid ultrasound. Arthritis Rheum 2002; 46(7): 1714‒9.
28. Ristić GG, Subota V, Lepić T, Stanisavljević D, Glišić B, Ristić AD, et al. Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis and Low Cardiovascular Risk: The Role of von Wil-lebrand Factor Activity. PLoS One 2015; 10(8): e013046.
29. Ristić GG, Lepić T, Glisić B, Stanisavljević D, Vojvodić D, Petronijević M, et al. Rheumatoid arthritis is an independent risk factor for increased carotid intima-media thickness: impact of anti-inflammatory treatment. Rheumatology (Oxford) 2010; 49(6): 1076‒81.
30. Ciftci O, Yilmaz S, Topcu S, Caliskan M, Gullu H, Erdogan D, et al. Impaired coronary microvascular function and increased in-tima-media thickness in rheumatoid arthritis. Atherosclerosis 2008; 198(2): 332‒7.
31. Kumeda Y, Inaba M, Goto H, Nagata M, Henmi Y, Furumitsu Y, et al. Increased thickness of the arterial intima-media detected by ultrasonography in patients with rheumatoid arthritis. Arthritis Rheum 2002; 46(6): 1489‒97.
32. van Sijl AM, Peters MJ, Knol DK, de Vet HC, Gonzalez-Gay MA, Smulders YM, et al. Carotid intima media thickness in rheuma-toid arthritis as compared to control subjects: a meta-analysis. Semin Arthritis Rheum 2011; 40(5): 389‒97.
33. Mohan A, Sada S, Kumar BS, Sarma KV, Devi BV, Rao PV, et al. Subclinical atherosclerosis in patients with rheumatoid arthritis by utilizing carotid intima-media thickness as a surrogate marker. Indian J Med Res 2014; 140(3): 379‒86.
34. Saigal R, Mathur V, Goyal L. Carotid intima media thickness as a marker of subclinical atherosclerosis in rheumatoid arthritis: a case control study. Int J Adv Med 2016; 3(4): 942‒6.
35. Roman MJ, Moeller E, Davis A, Paget SA, Crow MK, Lockshin MD, et al. Preclinical carotid atherosclerosis in patients with rheumatoid arthritis. Ann Intern Med 2006; 144(4): 249‒56.
36. Mahajan V, Handa R, Kumar U, Sharma S, Gulati G, Pandey RM, et al. Assessment of atherosclerosis by carotid intimomedial thickness in patients with rheumatoid arthritis. J Assoc Physi-cians India 2008; 56: 587‒90.
37. Corrales A, Vegas-Revenga N, Rueda-Gotor J, Portilla V, Atienza-Mateo B, Blanco R, et al. Carotid plaques as predictors of cardi-ovascular events in patients with Rheumatoid Arthritis. Results from a 5-year-prospective follow-up study. Semin Arthritis Rheum 2020; 50(6): 1333‒8.
38. Patel S, Bhatt K, Patel A, Madabhavi I, Gupta A, Zadafiya H, et al. A study of carotid intima-medial thickness as a primary marker of atherosclerosis in patients with rheumatoid arthritis. Int Cardiovasc Forum J 2016; 9: 31–5.
39. Abd El-Monem SM, Ali AY, Hashaad NI, Bendary AM, Abd El-Aziz HA. Association of rheumatoid arthritis disease activity, severity with electrocardiographic findings, and carotid artery atherosclerosis. Egypt Rheumatol Rehabil 2019; 46: 11‒20.
40. Semb AG, Rollefstad S, Provan SA, Kvien TK, Stranden E, Olsen IC, et al. Carotid plaque characteristics and disease activity in rheumatoid arthritis. J Rheumatol 2013; 40(4): 359‒68.
41. Ristić GG, Subota V, Stanisavljević D, Vojvodić D, Ristić AD, Glišić B, et al. Impact of disease activity on impaired glucose metabo-lism in patients with rheumatoid arthritis. Arthritis Res Ther 2021; 23(1): 95.
42. Jonsson SW, Backman C, Johnson O, Karp K, Lundström E, Sundqvist KG, et al. Increased prevalence of atherosclerosis in patients with medium term rheumatoid arthritis. J Rheumatol. 2001; 28(12): 2597‒602.
43. Cuomo G, Di Micco P, Niglio A, La Montagna G, Valentini G. Atherosclerosis and rheumatoid arthritis: relationships be-tween intima-media thickness of the common carotid arteries and disease activity and disability. Reumatismo 2004; 56(4): 242‒6. (Italian)
44. Bartoloni Bocci E, Marchesi S, Delle Monache F, Vaudo G, Giordano A, Ragni Alunni F, et al. Subclinical atherosclerosis in young patients with rheumatoid arthritis and low disease activity. Reumatismo 2005; 57(1): 16‒21. (Italian)
45. Biskup M, Biskup W, Majdan M, Targońska-Stępniak B. Cardio-vascular system changes in rheumatoid arthritis patients with continued low disease activity. Rheumatol Int 2018; 38(7): 1207‒15.
46. Del Rincón I, O'Leary DH, Freeman GL, Escalante A. Accelera-tion of atherosclerosis during the course of rheumatoid arthri-tis. Atherosclerosis 2007; 195(2): 354‒60.
47. González-Juanatey C, Llorca J, González-Gay MA. Correlation be-tween endothelial function and carotid atherosclerosis in rheumatoid arthritis patients with long-standing disease. Ar-thritis Res Ther 2011; 13(3): R101.
48. Youssef G, Allam NT, Gaber W, Afifi A, Hesham D. Increased ar-terial stiffness in rheumatoid arthritis and Its relation to disease activity: A cross sectional study. Egypt Heart J 2018; 70(1): 35‒40.
49. Wållberg-Jonsson S, Ohman M, Rantapää-Dahlqvist S. Which fac-tors are related to the presence of atherosclerosis in rheuma-toid arthritis? Scand J Rheumatol 2004; 33(6): 373‒9.
50. Gerli R, Sherer Y, Vaudo G, Schillaci G, Gilburd B, Giordano A, et al. Early atherosclerosis in rheumatoid arthritis: effects of smoking on thickness of the carotid artery intima media. Ann N Y Acad Sci 2005; 1051: 281‒90.
51. Gonzalez-Juanatey C, Llorca J, Testa A, Revuelta J, Garcia-Porrua C, Gonzalez-Gay MA. Increased prevalence of severe subclinical atherosclerotic findings in long-term treated rheumatoid arthri-tis patients without clinically evident atherosclerotic disease. Medicine (Baltimore) 2003; 82(6): 407–13.
52. Sahari NS, Shaharir SS, Ismail MR, Rajalingham S, Mohamed Said MS. Subclinical atherosclerosis among rheumatoid arthritis pa-tients without overt cardiovascular risk factors. Mod Rheu-matol 2014; 24(6): 920‒5.
53. Novikova DS, Popkova TV, Nasonov EL. The effect of anti-B-cell therapy on the development of atherosclerosis in patients with rheumatoid arthritis. Curr Pharm Des 2012; 18(11): 1512‒8.
54. Charles-Schoeman C. Cardiovascular disease and rheumatoid ar-thritis: an update. Curr Rheumatol Rep 2012; 14(5): 455‒62.