Investigation of the Association Between Carotid Artery Intima-Media Thickness (IMT) and Cardiac Risk Factors in Patients with Systemic Lupus Erythematosus

Author(s): Zahra Rezaieyazdi, Sima Sedighi, Masoumeh Salari*, Mohammadreza H. Fard, Mahmoud R. Azarpazhooh, Peyman S. Tabrizi, Jalil T. Afshari, Masoud Saghafi

Journal Name: Current Rheumatology Reviews

Volume 16 , Issue 2 , 2020

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: The relationship between SLE and traditional risk factors for cardiovascular events was evaluated.

Methods: The data regarding sixty patients with SLE and 30 healthy controls (age and sex matched) were gathered using SLEDAI forms. Venous blood (10mL) from all the participants was examined for hs-CRP, homocysteine, VCAM1, CBC, anti-DNA antibody, C3, C4, low-density lipoprotein (LDL), cholesterol, FBS and triglyceride.

The IMT of carotid arteries was determined bilaterally by ultrasound. Other measurements included insulin levels via Elisa (Linco/Millipore Corp) and the HOMA-IR index for insulin resistance.

Results: The mean age (in years) in the test and control groups was 28.8±10.3 (18-52) and 33.8±9.13 (18-48), respectively.

The average IMT in the test group was directly related to serum levels of VCAM1 (p<0.001), homocysteine (p<0.001), cholesterol (p<0.009), LDL (p<0.001), TG (p<0.001), and FPG (p=0.004). The association between other risk factors, insulin resistance, carotid IMT and SLEDAI, was nonexistent. Mean insulin and insulin resistance levels in all the participants were 0.43±2.06 µU/mL and 0.09±0.44, respectively. There was no significant difference between the test and control groups regarding serum insulin and insulin resistance levels (p=0.42 and p=0.9, respectively). None of the risk factors, such as hsCRP, VCAM1, or homocysteine, were shown to be related to insulin resistance (p=0.6, p=0.6, p=0.09, respectively).

Conclusion: Our findings did not show an increase in the prevalence of atherosclerosis in patients with SLE. There was no association between IMT and insulin resistance. However, the former was associated with FPG, total cholesterol, LDL, TG, homocystein and VCAM1.

Keywords: Intima-media thickness, systemic lupus erythematosus, SLEDAI, cholesterol, homocysteine, VCAM1.

[1]
Urowitz MB, Gladman D, Ibañez D, et al. Systemic Lupus International Collaborating Clinics.Atherosclerotic vascular events in a multinational inception cohort of systemic lupus erythematosus. Arthritis Care Res (Hoboken) 2010; 62(6): 881-7.
[http://dx.doi.org/10.1002/acr.20122] [PMID: 20535799]
[2]
Thomas G, Tam L, Tomlinson B, Li E. Accelerated atherosclerosis in patients with systemic lupus erythematosus: a review of the causes and possible prevention Hong Kong medical journal= Xianggang yi xue za zhi 2002; 8(1): 26-32.
[3]
Nikpour M, Urowitz MB, Gladman DD. Premature atherosclerosis in systemic lupus erythematosus. Rheum Dis Clin North Am; 2005; 31(2): 329-54.vii-viii..
[http://dx.doi.org/10.1016/j.rdc.2005.01.001]
[4]
Nossent J, Cikes N, Kiss E, et al. Current causes of death in systemic lupus erythematosus in Europe, 2000--2004: relation to disease activity and damage accrual. Lupus 2007; 16(5): 309-17.
[http://dx.doi.org/10.1177/0961203307077987] [PMID: 17576731]
[5]
Ippolito A, Petri M. An update on mortality in systemic lupus erythematosus. Clin Exp Rheumatol 2008; 26(5)(Suppl. 51): S72-9.
[PMID: 19026147]
[6]
Becker-Merok A, Nossent J. Prevalence, predictors and outcome of vascular damage in systemic lupus erythematosus. Lupus 2009; 18(6): 508-15.
[http://dx.doi.org/10.1177/0961203308099233] [PMID: 19395452]
[7]
Telles RW, Lanna CC, Sousa AJ, et al. Progression of carotid atherosclerosis in patients with systemic lupus erythematosus. Clin Rheumatol 2013; 32(9): 1293-300.
[http://dx.doi.org/10.1007/s10067-013-2264-9] [PMID: 23620348]
[8]
Chung CP, Solus JF, Oeser A, et al. Genetic variation and coronary atherosclerosis in patients with systemic lupus erythematosus. Lupus 2014; 23(9): 876-80.
[http://dx.doi.org/10.1177/0961203314530019] [PMID: 24699314]
[9]
Reveille JD, Bartolucci A, Alarcón GS. Prognosis in systemic lupus erythematosus. Negative impact of increasing age at onset, black race, and thrombocytopenia, as well as causes of death. Arthritis Rheum 1990; 33(1): 37-48.
[http://dx.doi.org/10.1002/art.1780330105] [PMID: 2302266]
[10]
Sheane B, Urowitz M, Gladman D. Atherosclerosis in systemic lupus erythematus-epidemiology, risk faktors, subclinical assessment and future study. Atherosclerosis in systemic lupus erythematus-epidemiology, risk faktors, subclinical assessment and future study Rheu-matol Curr Res 2013. S5: 004.
[11]
Roman MJ, Shanker B-A, Davis A, et al. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med 2003; 349(25): 2399-406.
[http://dx.doi.org/10.1056/NEJMoa035471] [PMID: 14681505]
[12]
Asanuma Y, Oeser A, Shintani AK, et al. Premature coronary-artery atherosclerosis in systemic lupus erythematosus. N Engl J Med 2003; 349(25): 2407-15.
[http://dx.doi.org/10.1056/NEJMoa035611] [PMID: 14681506]
[13]
de Carvalho JF, Bonfá E, Borba EF. Systemic lupus erythematosus and “lupus dyslipoproteinemia”. Autoimmun Rev 2008; 7(3): 246-50.
[http://dx.doi.org/10.1016/j.autrev.2007.11.016] [PMID: 18190886]
[14]
Magder LS, Petri M. Incidence of and risk factors for adverse cardiovascular events among patients with systemic lupus erythematosus. Am J Epidemiol 2012; 176(8): 708-19.
[http://dx.doi.org/10.1093/aje/kws130] [PMID: 23024137]
[15]
Sabio JM, Vargas-Hitos J, Zamora-Pasadas M, et al. Grupo Lupus Virgen de las Nieves. Metabolic syndrome is associated with increased arterial stiffness and biomarkers of subclinical atherosclerosis in patients with systemic lupus erythematosus. J Rheumatol 2009; 36(10): 2204-11.
[http://dx.doi.org/10.3899/jrheum.081253] [PMID: 19723903]
[16]
Peng SL. Fas (CD95)-related apoptosis and rheumatoid arthritis. Rheumatology (Oxford) 2006; 45(1): 26-30.
[http://dx.doi.org/10.1093/rheumatology/kei113] [PMID: 16159946]
[17]
Wallace DJ. What’s new in the management of lupus since 2000? J Clin Rheumatol 2006; 12(6): 307-13.
[http://dx.doi.org/10.1097/01.rhu.0000250481.90932.7b] [PMID: 17149066]
[18]
Roman MJ, Crow MK, Lockshin MD, et al. Rate and determinants of progression of atherosclerosis in systemic lupus erythematosus. Arthritis Rheum 2007; 56(10): 3412-9.
[http://dx.doi.org/10.1002/art.22924] [PMID: 17907140]
[19]
Bruce IN, Urowitz MB, Gladman DD, Ibañez D, Steiner G. Risk factors for coronary heart disease in women with systemic lupus erythematosus: the Toronto Risk Factor Study. Arthritis Rheum 2003; 48(11): 3159-67.
[http://dx.doi.org/10.1002/art.11296] [PMID: 14613278]
[20]
Perna M, Roman MJ, Alpert DR, et al. Relationship of asymmetric dimethylarginine and homocysteine to vascular aging in systemic lupus erythematosus patients. Arthritis Rheum 2010; 62(6): 1718-22.
[http://dx.doi.org/10.1002/art.27392] [PMID: 20155836]
[21]
Petri M, Roubenoff R, Dallal GE, Nadeau MR, Selhub J, Rosenberg IH. Plasma homocysteine as a risk factor for atherothrombotic events in systemic lupus erythematosus. Lancet 1996; 348(9035): 1120-4.
[http://dx.doi.org/10.1016/S0140-6736(96)03032-2] [PMID: 8888164]
[22]
Rahman P, Gladman DD, Urowitz MB, Hallett D, Tam LS. Early damage as measured by the SLICC/ACR damage index is a predictor of mortality in systemic lupus erythematosus. Lupus 2001; 10(2): 93-6.
[http://dx.doi.org/10.1191/096120301670679959] [PMID: 11237132]
[23]
Lopez R, Davidson JE, Beeby MD, Egger PJ, Isenberg DA. Lupus disease activity and the risk of subsequent organ damage and mortality in a large lupus cohort. Rheumatology (Oxford) 2012; 51(3): 491-8.
[http://dx.doi.org/10.1093/rheumatology/ker368] [PMID: 22109798]
[24]
Kahlenberg JM, Kaplan MJ. Mechanisms of premature atherosclerosis in rheumatoid arthritis and lupus. Annu Rev Med 2013; 64: 249-63.
[http://dx.doi.org/10.1146/annurev-med-060911-090007] [PMID: 23020882]
[25]
Grönwall C, Reynolds H, Kim JK, et al. Relation of carotid plaque with natural IgM antibodies in patients with systemic lupus erythematosus. Clin Immunol 2014; 153(1): 1-7.
[http://dx.doi.org/10.1016/j.clim.2014.03.017] [PMID: 24704464]
[26]
Gladman DD, Urowitz MB, Rahman P, Ibañez D, Tam L-S. Accrual of organ damage over time in patients with systemic lupus erythematosus. J Rheumatol 2003; 30(9): 1955-9.
[PMID: 12966597]
[27]
Petri M, Purvey S, Fang H, Magder LS. Predictors of organ damage in systemic lupus erythematosus: the Hopkins Lupus Cohort. Arthritis Rheum 2012; 64(12): 4021-8.
[http://dx.doi.org/10.1002/art.34672] [PMID: 22932985]
[28]
Avalos I, Chung CP, Oeser A, et al. Aspirin therapy and thromboxane biosynthesis in systemic lupus erythematosus. Lupus 2007; 16(12): 981-6.
[http://dx.doi.org/10.1177/0961203307083313] [PMID: 18042592]
[29]
Ferreira GA, Navarro TP, Telles RW, Andrade LE, Sato EI. Atorvastatin therapy improves endothelial-dependent vasodilation in patients with systemic lupus erythematosus: an 8 weeks controlled trial. Rheumatology (Oxford) 2007; 46(10): 1560-5.
[http://dx.doi.org/10.1093/rheumatology/kem186] [PMID: 17693444]
[30]
Cacciapaglia F, Zardi EM, Coppolino G, et al. Stiffness parameters, intima-media thickness and early atherosclerosis in systemic lupus erythematosus patients. Lupus 2009; 18(3): 249-56.
[http://dx.doi.org/10.1177/0961203308097571] [PMID: 19213864]
[31]
Yildiz M, Yildiz BS, Soy M, Tutkan H. Impairment of arterial distensibility in premenopausal women with systemic lupus erythematosus. Kardiol Pol[Polish Heart Journal] 2008; 66(11): 1194-9.
[PMID: 19105096]
[32]
Eder L, Gladman DD, Ibañez D, Urowitz MB. The correlation between carotid artery atherosclerosis and clinical ischemic heart disease in lupus patients. Lupus 2014; 23(11): 1142-8.
[http://dx.doi.org/10.1177/0961203314537696] [PMID: 24876099]
[33]
Koca SS, Karaca I, Yavuzkir MF, et al. Insulin resistance is related with oxidative stress in systemic lupus erythematosus. Anadolu Kardiyol Derg 2009; 9(1): 23-8.
[PMID: 19196569]
[34]
Goldberg RJ, Urowitz MB, Ibañez D, Nikpour M, Gladman DD. Risk factors for development of coronary artery disease in women with systemic lupus erythematosus. J Rheumatol 2009; 36(11): 2454-61.
[http://dx.doi.org/10.3899/jrheum.090011] [PMID: 19833754]
[35]
Frostegård J, Wu R, Giscombe R, Holm G, Lefvert AK, Nilsson J. Induction of T-cell activation by oxidized low density lipoprotein. Arterioscler Thromb 1992; 12(4): 461-7.
[http://dx.doi.org/10.1161/01.ATV.12.4.461] [PMID: 1558837]
[36]
Bruce IN, Urowitz MB, Gladman DD, Hallett DC. Natural history of hypercholesterolemia in systemic lupus erythematosus. J Rheumatol 1999; 26(10): 2137-43.
[PMID: 10529129]
[37]
Thompson T, Sutton-Tyrrell K, Wildman RP, et al. Progression of carotid intima-media thickness and plaque in women with systemic lupus erythematosus. Arthritis Rheum 2008; 58(3): 835-42.
[http://dx.doi.org/10.1002/art.23196] [PMID: 18311797]
[38]
Tselios K, Sheane BJ, Gladman DD, Urowitz MB. Optimal Monitoring For Coronary Heart Disease Risk in Patients with Systemic Lupus Erythematosus: A Systematic Review. J Rheumatol 2016; 43(1): 54-65.
[http://dx.doi.org/10.3899/jrheum.150460] [PMID: 26568591]
[39]
Kiani AN, Fang H, Akhter E, et al. Apolipoprotein-containing lipoprotein subclasses and subclinical atherosclerosis in systemic lupus erythematosus. Arthritis Care Res (Hoboken) 2015; 67(3): 442-6.
[http://dx.doi.org/10.1002/acr.22430] [PMID: 25155365]
[40]
Esdaile JM, Abrahamowicz M, Grodzicky T, et al. Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. Arthritis Rheum 2001; 44(10): 2331-7.
[http://dx.doi.org/10.1002/1529-0131(200110)44:10<2331:AID-ART395>3.0.CO;2-I] [PMID: 11665973]
[41]
O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Cardiovascular Health Study Collaborative Research Group.Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. N Engl J Med 1999; 340(1): 14-22.
[http://dx.doi.org/10.1056/NEJM199901073400103] [PMID: 9878640]
[42]
Lakka H-M, Laaksonen DE, Lakka TA, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002; 288(21): 2709-16.
[http://dx.doi.org/10.1001/jama.288.21.2709] [PMID: 12460094]
[43]
Hung J, McQuillan BM, Chapman CM, Thompson PL, Beilby JP. Elevated interleukin-18 levels are associated with the metabolic syndrome independent of obesity and insulin resistance. Arterioscler Thromb Vasc Biol 2005; 25(6): 1268-73.
[http://dx.doi.org/10.1161/01.ATV.0000163843.70369.12] [PMID: 15790931]
[44]
Santos MJ, Fonseca JE. Metabolic syndrome, inflammation and atherosclerosis - the role of adipokines in health and in systemic inflammatory rheumatic diseases. Acta Reumatol Port 2009; 34(4): 590-8.
[PMID: 20852572]
[45]
Chung CP, Avalos I, Oeser A, et al. High prevalence of the metabolic syndrome in patients with systemic lupus erythematosus: association with disease characteristics and cardiovascular risk factors. Ann Rheum Dis 2007; 66(2): 208-14.
[http://dx.doi.org/10.1136/ard.2006.054973] [PMID: 16901956]
[46]
Tso TK, Huang W-N. Elevation of fasting insulin and its association with cardiovascular disease risk in women with systemic lupus erythematosus. Rheumatol Int 2009; 29(7): 735-42.
[http://dx.doi.org/10.1007/s00296-008-0781-7] [PMID: 19037607]
[47]
El Magadmi M, Ahmad Y, Turkie W, et al. Hyperinsulinemia, insulin resistance, and circulating oxidized low density lipoprotein in women with systemic lupus erythematosus. J Rheumatol 2006; 33(1): 50-6.
[PMID: 16395749]
[48]
Posadas-Romero C, Torres-Tamayo M, Zamora-González J, et al. High insulin levels and increased low-density lipoprotein oxidizability in pediatric patients with systemic lupus erythematosus. Arthritis Rheum 2004; 50(1): 160-5.
[http://dx.doi.org/10.1002/art.11472] [PMID: 14730612]
[49]
Smith GD, Amos TA, Mahler R, Peters TJ. Effect of chloroquine on insulin and glucose homoeostasis in normal subjects and patients with non-insulin-dependent diabetes mellitus. Br Med J (Clin Res Ed) 1987; 294(6570): 465-7.
[http://dx.doi.org/10.1136/bmj.294.6570.465] [PMID: 3103729]
[50]
de Leeuw K, Smit AJ, de Groot E, van Roon AM, Kallenberg CG, Bijl M. Longitudinal study on premature atherosclerosis in patients with systemic lupus erythematosus. Atherosclerosis 2009; 206(2): 546-50.
[http://dx.doi.org/10.1016/j.atherosclerosis.2009.03.018] [PMID: 19389674]
[51]
Rua-Figueroa I, Arencibia-Mireles O, Elvira M, et al. Factors involved in the progress of preclinical atherosclerosis associated with systemic lupus erythematosus: a 2-year longitudinal study. Ann Rheum Dis 2010; 69(6): 1136-9.
[http://dx.doi.org/10.1136/ard.2008.104349] [PMID: 19687018]
[52]
Roldan CA, Joson J, Sharrar J, Qualls CR, Sibbitt WL Jr. Premature aortic atherosclerosis in systemic lupus erythematosus: a controlled transesophageal echocardiographic study. J Rheumatol 2010; 37(1): 71-8.
[http://dx.doi.org/10.3899/jrheum.090665] [PMID: 19955049]
[53]
Valdivielso P, Gómez-Doblas JJ, Macias M, et al. Lupus-associated endothelial dysfunction, disease activity and arteriosclerosis. Clin Exp Rheumatol 2008; 26(5): 827-33.
[PMID: 19032815]
[54]
Reiss AB, Wan DW, Anwar K, et al. Enhanced CD36 scavenger receptor expression in THP-1 human monocytes in the presence of lupus plasma: linking autoimmunity and atherosclerosis. Exp Biol Med (Maywood) 2009; 234(3): 354-60.
[http://dx.doi.org/10.3181/0806-BC-194] [PMID: 19144874]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 2
Year: 2020
Page: [125 - 133]
Pages: 9
DOI: 10.2174/1573397116666191217122030
Price: $65

Article Metrics

PDF: 14
HTML: 1