Subclinical Atherosclerosis and Oxidized LDL Levels in Familial Mediterranean Fever

Serdal Uğurlu; Sanem Nemmezi Karaca; Yeltekin Demirel; Emire Seyahi

doi:10.7197/cmj.1131483

EN

Subclinical Atherosclerosis and Oxidized LDL Levels in Familial Mediterranean Fever

Abstract

Objective: To investigate markers of carotid atherosclerosis and oxidized low density lipoprotein (OxLDL) levels in patients with Familial Mediterranean Fever (FMF) who have no risk factors for cardiovascular disease.

Method: It was included 44 patients (25 F/19 M; mean age: 33.5±7.5) with FMF in attack free period and gender and age matched 44 healthy subjects (25 F/19 M; mean age: 33.4±7.0). The patients with clinical coronary artery disease, chronic renal disease, diabetes mellitus, hypertension, history of myocardial infarction, angina pectoris, cerebrovascular disease, dyslipidemia, metabolic syndrome, active infection, those in postmenopausal period, and those using anti-lipid drugs were excluded. Carotid artery intima-media thickness (C-IMT) was measured and investigated atherosclerotic plaques in the carotids by using doppler ultrasound. Serum lipid and OxLDL levels were also assessed. Data were analyzed with the SPSS program and p<0.05 were accepted as significant.

Result: Mean disease duration of the FMF patients was 20±9 years. The mean C-IMT did not differ between the patient and control groups (0.52±0.10 mm, 0.53±0.06 mm, respectively, p=0.709). None of the patients or controls had atherosclerotic plaques. Total and LDL cholesterol levels were significantly lower in the patient group compared to the controls (total cholesterol: 157.07±34.18, 181.05±36.79, respectively, p=0.002; LDL cholesterol: 100.48±30.13, 126.25±34.05, respectively, p=0.001). However, we found that OxLDL levels were significantly higher in FMF patients compared to control group (337.48±438.56 ng/dl, 156.19±383.24 ng/dl, p=0.044). No correlation was found between C-IMT and OxLDL levels in both patients (p=0.324) and controls (p=0.246).

Conclusion: Our study provides further evidence for no increased atherosclerosis in FMF. As previously shown, FMF patients have lower cholesterol levels compared to healthy controls. On the other hand, increased OxLDL levels could be associated with increased subclinical inflammation.

Keywords

Destekleyen Kurum

Cumhuriyet University Scientific Research Projects (CÜBAP)

Proje Numarası

T402

Teşekkür

Researchers thank to Emrah GÜNEY, MD, for measurement of carotid artery intima media thickness and investigation of atherosclerotic plaques, by using doppler ultrasound.

Kaynakça

Referans1. Alghamdi M. Familial Mediterranean fever, review of the literature. Clin Rheumatol. 2017;36(8):1707-1713. doi: 10.1007/s10067-017-3715-5.
Referans2. Manukyan G, Aminov R. Update on Pyrin Functions and Mechanisms of Familial Mediterranean Fever. Front Microbiol. 2016;7:456. doi:10.3389/fmicb.2016.00456.
Referans3. Gasparyan AY, Ayvazyan L, Yessirkepov M, Kitas GD. Colchicine as an anti-inflammatory and cardioprotective agent. Expert Opin Drug Metab Toxicol 2015;11:1781-94.
Referans4. Ben-Zvi I, Livneh A. Chronic inflammation in FMF: markers, risk factors, outcomes and therapy. Nat Rev Rheumatol. 2011;7(2):105-12. doi: 10.1038/nrrheum.2010.181.
Referans5. Hansson GK, Hermansson A. The immune system in atherosclerosis. Nat Immunol 2011;12:204-12.
Referans6. Myasoedova E, Chandran A, Ilhan B, 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(3):560-5. doi: 10.1136/annrheumdis-2014-206411.
Referans7. Han C, Robinson DW Jr, Hackett MV, et al. Cardiovascular disease and risk factors in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. J Rheumatol. 2006;33(11):2167-72.
Referans8. Roifman I, Beck PL, Anderson TJ, Eisenberg MJ, Genest J. Chronic inflammatory diseases and cardiovascular risk: a systematic review. Can J Cardiol. 2011;27(2):174-82. doi: 10.1016/j.cjca.2010.12.040.

Referans9. Wılson PW. Evidence of systemic inflammation and estimation of coronary artery disease risk: a population perspective. Am J Med 2008;121(Suppl. 10): S15-20.
Referans10. Hahn BH, Grossman J, Chen W, McMahon M. The pathogenesis of atherosclerosis in autoimmune rheumatic diseases: roles of inflammation and dyslipidemia. J Autoimmun. 2007;28(2-3):69-75. doi: 10.1016/j.jaut.2007.02.004.
Referans11. Giles JT, Szklo M, Post W, et al. Coronary arterial calcification in rheumatoid arthritis: comparison with the Multi-Ethnic Study of Atherosclerosis. Arthritis Res Ther. 2009;11(2):R36. doi: 10.1186/ar2641.
Referans12. Horreau C, Pouplard C, Brenaut E, et al. Cardiovascular morbidity and mortality in psoriasis and psoriatic arthritis: a systematic literature review. J Eur Acad Dermatol Venereol. 2013 Aug;27 Suppl 3:12-29. doi: 10.1111/jdv.12163.
Referans13. Lindhardsen J, Ahlehoff O, Gislason GH, et al. The risk of myocardial infarction in rheumatoid arthritis and diabetes mellitus: a Danish nationwide cohort study. Ann Rheum Dis. 2011;70(6):929-34. doi: 10.1136/ard.2010.143396.
Referans14. Dregan A, Chowienczyk P, Molokhia M. Cardiovascular and type 2 diabetes morbidity and all-cause mortality among diverse chronic inflammatory disorders. Heart. 2017;103(23):1867-1873. doi: 10.1136/heartjnl-2017-311214.
Referans15. del Rincón ID, Williams K, Stern MP, Freeman GL, Escalante A. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum. 2001;44(12):2737-45.
Referans16. Canpolat U, Yorgun H, Aytemir K, et al. Cardiovascular risk and coronary atherosclerotic plaques detected by multidetector computed tomography.Framingham and SCORE risk models underestimate coronary atherosclerosis in the symptomatic low-risk Turkish population. Coronary Artery Disease. 2012;23(3):195-200. doi: 10.1097/MCA.0b013e3283511608.
Referans17. Tunca M, Akar S, Onen F, et al. Turkish FMF Study Group. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine (Baltimore): 2005;84(1):1-11. doi: 10.1097/01.md.0000152370.84628.0c.
Referans18. Langevitz P, Livneh A, Neumann L, et al. Prevalence of ischemic heart disease in patients with familial Mediterranean fever. Isr Med Assoc J. 2001;3(1):9-12.
Referans19. Lidar M, Scherrmann JM, Shinar Y, et al. Colchicine nonresponsiveness in familial Mediterranean fever: clinical, genetic, pharmacokinetic, and socioeconomic characterization. Semin Arthritis Rheum. 2004;33(4):273-82. doi: 10.1053/s0049-0172(03)00137-9.
Referans20. Livneh A, Langevitz P, Zemer D, et al. Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum. 1997;40(10):1879-85. doi: 10.1002/art.1780401023.
Referans21. O'Leary DH, Polak JF, Wolfson SK Jr, et al. Use of sonography to evaluate carotid atherosclerosis in the elderly. The Cardiovascular Health Study. CHS Collaborative Research Group. Stroke. 1991;22(9):1155-63. doi: 10.1161/01.str.22.9.1155.
Referans22. Lachmann HJ, Sengül B, Yavuzşen TU, et al. Clinical and subclinical inflammation in patients with familial Mediterranean fever and in heterozygous carriers of MEFV mutations. Rheumatology (Oxford). 2006;45(6):746-50. doi: 10.1093/rheumatology/kei279.
Referans23. Yüksel S, Ayvazyan L, Gasparyan AY. Familial mediterranean Fever as anemerging clinical model of atherogenesis associated with low-grade inflammation. Open Cardiovasc Med J. 2010;4:51–56.
Referans24. 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):2331-2337.
Referans25. Ugurlu S, Seyahi E, Cetinkaya F, et al. Intima-media thickening in patients with familial Mediterranean fever. Rheumatology (Oxford). 2009;48(8):911-5.
Referans26. Akdogan A, Calguneri M, Yavuz B, et al. Are Familial Mediterranean Fever (FMF) Patients at Increased Risk for Atherosclerosis? Impaired Endothelial Function and Increased Intima Media Thickness Are Found in FMF. J Am Coll Cardiol. 2006;48(11):2351–2353. https://doi.org/10.1016/j.jacc.2006.09.013.
Referans27. Peru H, Altun B, Doğan M, et al. The evaluation of carotid intima-media thickness in children with familial Mediterranean fever. Clin Rheumatol. 2008;27(6):689-94. doi: 10.1007/s10067-007-0764-1.
Referans28. Sari I, Karaoglu O, Can G, et al. Early ultrasonographic markers of atherosclerosis in patients with familial Mediterranean fever. Clin Rheumatol. 2007;26:1467–1473. https://doi.org/10.1007/s10067-006-0529-2.
Referans29. Bilginer Y, Ozaltin F, Basaran C, et al. Evaluation of intima media thickness of the common and internal carotid arteries with inflammatory markers in familial Mediterranean fever as possible predictors for atherosclerosis. Rheumatol Int. 2008;28(12):1211-6. doi: 10.1007/s00296-008-0605-9.
Referans30. Kucuk A, Uslu AU, Arslan S, et al. Ischemia-Modified Albumin and Atherosclerosis in Patients With Familial Mediterranean Fever. Angiology. 2016 May;67(5):456-60.
Referans31. Mohamed R, El-Bassyouni HT, Elwan SH, et al. Carotid intima-media thickness, lipid profile, serum amyloid A and vitamin D status in children with familial Mediterranean fever. The Egyptian Rheumatologist, 2020;42(3):237-240.
Referans32. Kurban S, Mehmetoğlu İ. Antibodies Against Oxidized Low Density Lipoprotein and Their Clinical İmportance: Review. Turkiye Klinikleri J Med Sci. 2005;25:73-84.
Referans33. Steinerová A, Racek J, Stozický F, et al. Antibodies against oxidized LDL--theory and clinical use. Physiol Res. 2001;50(2):131-141.
Referans34. Morganelli PM, Rogers RA, Kitzmiller TJ, Bergeron A. Enhanced metabolism of LDL aggregates mediated by specific human monocyte IgG Fc receptors. J Lipid Res. 1995;36(4):714-724.
Referans35. Salonen JT, Ylä-Herttuala S, Yamamoto R, et al. Autoantibody against oxidised LDL and progression of carotid atherosclerosis. Lancet. 1992;339(8798):883-7. doi: 10.1016/0140-6736(92)90926-t.
Referans36. Engelen SE, Robinson AJB, Zurke YX, Monaco C. Therapeutic strategies targeting inflammation and immunity in atherosclerosis: how to proceed?. Nat Rev Cardiol. 2022:1-21. Online ahead of print. https://doi.org/10.1038/s41569-021-00668-4.
Referans37. Sherer Y, Zinger H, Shoenfeld Y. Atherosclerosis in systemic lupus erythematosus. Autoimmunity 2010:43;98–102.
Referans38. Bassi N, Zampieri S, Ghirardello A, et al. OxLDL/beta2GPI complex and anti-oxLDL/beta2GPI in SLE: prevalence and correlates. Autoimmunity. 2009;42:289-91.
Referans39. Ahmed HM, Youssef M, Mosaad YM. Antibodies against oxidized low-density lipoprotein are associated with subclinical atherosclerosis in recent-onset rheumatoid arthritis. Clin Rheumatol. 2010;29(11):1237-43. doi: 10.1007/s10067-010-1436-0.
Referans40. Orem A, Yandi YE, Vanizor B, et al. The evaluation of autoantibodies against oxidatively modified low-density lipoprotein (LDL), susceptibility of LDL to oxidation, serum lipids and lipid hydroperoxide levels, total antioxidant status, antioxidant enzyme activities, and endothelial dysfunction in patients with Behçet's disease. Clin Biochem. 2002;35(3):217-24. doi: 10.1016/s0009-9120(02)00290-4.
Referans41. Cimen F, Yildirmak ST, Ergen A, et al. Serum Lipid, Lipoprotein and Oxidatively Modified Low Density Lipoprotein Levels in Active or Inactive Patients with Behçet's Disease. Indian J Dermatol. 2012;57(2):97-101. doi: 10.4103/0019-5154.94273.
Referans42. Acay A, Ulu MS, Ahsen A, et al. Atherogenic index as a predictor of atherosclerosis in subjects with familial Mediterranean fever. Medicina (Kaunas). 2014;50(6):329-33. doi: 10.1016/j.medici.2014.11.009.
Referans43. Çakırca G, Çelik MM. Lipid profile and atherogenic indices and their association with platelet indices in familial Mediterranean fever. Turk Kardiyol Dern Ars. 2018;46(3):184-190. doi: 10.5543/tkda.2018.93762.
Referans44. Ugurlu S, Seyahi E, Hanci I, et al. Effect of colchicine on serum lipid levels. Clin Exp Rheumatol. 2016;34(6 Suppl 102):S136.

Ayrıntılar

Birincil Dil

İngilizce

Konular

Sağlık Kurumları Yönetimi

Bölüm

Araştırma Makalesi

Yazarlar

Serdal Uğurlu
0000-0002-9561-2282
Türkiye

Sanem Nemmezi Karaca ^*
0000-0002-4853-8366
Türkiye

Yeltekin Demirel
0000-0002-6105-0293
Türkiye

Emire Seyahi
0000-0003-4965-2918
Türkiye

Yayımlanma Tarihi

30 Haziran 2022

Gönderilme Tarihi

15 Haziran 2022

Kabul Tarihi

19 Haziran 2022

Yayımlandığı Sayı

Yıl 2022 Cilt: 44 Sayı: 2

DOI

https://doi.org/10.7197/cmj.1131483

IZ

https://izlik.org/JA27ZE35ZB

Kaynak Göster

RIS / Bibtex

AMA

1.Uğurlu S, Nemmezi Karaca S, Demirel Y, Seyahi E. Subclinical Atherosclerosis and Oxidized LDL Levels in Familial Mediterranean Fever. CMJ. 2022;44(2):181-191. doi:10.7197/cmj.1131483

Öz

Subclinical Atherosclerosis and Oxidized LDL Levels in Familial Mediterranean Fever

Abstract

Keywords

Destekleyen Kurum

Proje Numarası

Teşekkür

Kaynakça

Ayrıntılar

Birincil Dil

Konular

Bölüm

Yazarlar

Yayımlanma Tarihi

Gönderilme Tarihi

Kabul Tarihi

Yayımlandığı Sayı

DOI

IZ

Kaynak Göster