Clinical Rheumatology

, Volume 26, Issue 9, pp 1467–1473

Early ultrasonographic markers of atherosclerosis in patients with familial Mediterranean fever

  • Ismail Sari
  • Oguzhan Karaoglu
  • Gercek Can
  • Servet Akar
  • Aytac Gulcu
  • Merih Birlik
  • Nurullah Akkoc
  • Mehmet Tunca
  • Yigit Goktay
  • Fatos Onen
Original Article


Systemic inflammation plays an important role in the development of atherosclerosis (AS). The aim of this study was to evaluate the presence of early AS in patients with familial Mediterranean fever (FMF) that is characterized by recurrent inflammatory attacks of serositis. Sixty-one FMF patients (30 Male/31 Female; 31.5 [18–54] years) and 31 healthy controls (16 Male/15 Female; 31 [22–58] years) were studied. All FMF patients were on regular daily colchicine treatment and during attack-free periods. Both the FMF patients and controls with a history of diabetes mellitus (DM), hypertension, and hyperlipidemia were excluded. Body mass index (BMI) was calculated. Serum lipids, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were assessed. Two-hour oral glucose tolerance test was performed to rule out DM and glucose intolerance. To investigate early AS “endothelium-dependent flow-mediated dilatation (FMD%),” “nitroglycerin-induced endothelium-independent peripheral vasodilatation (NTG%),” and intima-media thickness (IMT) of common carotid arteries (CCA) were measured by ultrasonograpy. The median disease duration for FMF patients was 16 (1–45) years. Age, sex, BMI, smoking status, and serum lipids were comparable in patients and controls (p > 0.05). However, ESR and standard CRP were significantly higher in the patients group (p < 0.05). There were no differences in the measurements of right, left, and averaged IMT of CCA between patients and controls ([0.49 vs 0.5], [0.51 vs 0.52] and [0.5 vs 0.51]; p > 0.05, respectively). None of the subjects had carotid artery plaques. FMD% and NTG% were also similar in patients and controls group ([18.2 vs 20.6] and [24.2 vs 22.5]; p > 0.05, respectively). This study suggests that the markers of early AS are not impaired in FMF patients on regular daily colchicine treatment.


Arteriosclerosis Familial mediterranean fever Ultrasonography 





brachial artery diameter


body mass index


common carotid artery


C-reactive protein




diabetes mellitus


erythrocyte sedimentation rate


flow-mediated dilatation


familial Mediterranean fever


high density lipoprotein




intima-media thickness


low density lipoprotein




rheumatoid arthritis


systemic lupus erythematosus


Statistical Package of Social Science


total cholesterol




  1. 1.
    Sohar E, Gafni J, Pras M, Heller H (1967) Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med 43(2):227–53 (Aug)PubMedCrossRefGoogle Scholar
  2. 2.
    Onen F (2006) Familial mediterranean fever. Rheumatol Int 26(6):489–496 (Apr)PubMedCrossRefGoogle Scholar
  3. 3.
    Lachmann HJ, Sengul B, Yavuzsen TU, Booth DR, Booth SE, Bybee A et al (2006) Clinical and subclinical inflammation in patients with familial Mediterranean fever and in heterozygous carriers of MEFV mutations. Rheumatol (Oxf) 45:746-750 (Feb 9)CrossRefGoogle Scholar
  4. 4.
    Tunca M, Kirkali G, Soyturk M, Akar S, Pepys MB, Hawkins PN (1999) Acute phase response and evolution of familial Mediterranean fever. Lancet 353(9162):1415 (Apr 24)PubMedCrossRefGoogle Scholar
  5. 5.
    Zemer D, Pras M, Sohar E, Modan M, Cabili S, Gafni J (1986) Colchicine in the prevention and treatment of the amyloidosis of familial Mediterranean fever. N Engl J Med 314(16):1001–1005 (Apr 17)PubMedCrossRefGoogle Scholar
  6. 6.
    Bacon PA, Stevens RJ, Carruthers DM, Young SP, Kitas GD (2002) Accelerated atherogenesis in autoimmune rheumatic diseases. Autoimmun Rev 1(6):338–347 (Dec)PubMedCrossRefGoogle Scholar
  7. 7.
    Manzi S, Wasko MC (2000) Inflammation-mediated rheumatic diseases and atherosclerosis. Ann Rheum Dis 59(5):321–325 (May)PubMedCrossRefGoogle Scholar
  8. 8.
    Haskard DO (2004) Accelerated atherosclerosis in inflammatory rheumatic diseases. Scand J Rheumatol 33(5):281–292PubMedCrossRefGoogle Scholar
  9. 9.
    Peters MJ, Van der Horst-Bruinsma IE, Dijkmans BA, Nurmohamed MT (2004) Cardiovascular risk profile of patients with spondylarthropathies, particularly ankylosing spondylitis and psoriatic arthritis. Semin Arthritis Rheum 34(3):585–592 (Dec)PubMedCrossRefGoogle Scholar
  10. 10.
    Meyer O (2001) Atherosclerosis and connective tissue diseases. Jt Bone Spine 68(6):564–575 (Dec)CrossRefGoogle Scholar
  11. 11.
    Poredos P (2004) Intima-media thickness: indicator of cardiovascular risk and measure of the extent of atherosclerosis. Vasc Med 9(1):46–54 (Feb)PubMedCrossRefGoogle Scholar
  12. 12.
    Raitakari OT, Celermajer DS (2000) Flow-mediated dilatation. Br J Clin Pharmacol 50(5):397–404 (Nov)PubMedCrossRefGoogle Scholar
  13. 13.
    Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362(6423):801–809 (Apr 29)PubMedCrossRefGoogle Scholar
  14. 14.
    Van Doornum S, McColl G, Jenkins A, Green DJ, Wicks IP (2003) Screening for atherosclerosis in patients with rheumatoid arthritis: comparison of two in vivo tests of vascular function. Arthritis Rheum 48(1):72–80 (Jan)PubMedCrossRefGoogle Scholar
  15. 15.
    Lima DS, Sato EI, Lima VC, Miranda F Jr, Hatta FH (2002) Brachial endothelial function is impaired in patients with systemic lupus erythematosus. J Rheumatol 29(2):292–297 (Feb)PubMedGoogle Scholar
  16. 16.
    Oflaz H, Mercanoglu F, Karaman O, Kamali S, Erer B, Genchellac H et al (2005) Impaired endothelium-dependent flow-mediated dilation in Behçet’s disease: more prominent endothelial dysfunction in patients with vascular involvement. Int J Clin Pract 59(7):777–781 (Jul)PubMedCrossRefGoogle Scholar
  17. 17.
    Sari I, Okan T, Akar S, Cece H, Altay C, Secil M et al (2006) Impaired endothelial function in patients with ankylosing spondylitis. Rheumatol (Oxf) 45(3):283–286 (Mar)CrossRefGoogle Scholar
  18. 18.
    Langevitz P, Livneh A, Neumann L, Buskila D, Shemer J, Amolsky D et al (2001) Prevalence of ischemic heart disease in patients with familial Mediterranean fever. Isr Med Assoc J 3(1):9–12 (Jan)PubMedGoogle Scholar
  19. 19.
    Akdogan A, Calguneri M, Kalyoncu U, Yavuz B, Karadag O, Aytemir K et al (2005) Endothelium-dependent flow-mediated dilatation is impaired in Familial Mediterranean Fever. Ann Rheum Dis 64(Suppl III):542Google Scholar
  20. 20.
    Bilginer Y, Basaran C, Ozaltin F, Besbas N, Topaloglu R, Ozen S et al (2006) Long term implications of inflammation in Familial Meditereanean Fever assessed by intima media thickness: a predictor for atherosclerosis?. Ann Rheum Dis 65 (Suppl II):100Google Scholar
  21. 21.
    Seyahi E, Ugurlu S, Cumali R, Balci H, Yazici H, Ozdogan H (2005) Subclinical atherosclerosis in familial Mediterranean fever. Proceedings of the 4th international congress on systemic autoinflammatory diseases “FMF and Beyond”. Bethesda, MDGoogle Scholar
  22. 22.
    Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T et al (1997) Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 40(10):1879–1885 (Oct)PubMedCrossRefGoogle Scholar
  23. 23.
    (1997) Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 20(7):1183–1197 (Jul)Google Scholar
  24. 24.
    Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P et al (2000) Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. Bmj 321(7255):199–204 (Jul 22)PubMedCrossRefGoogle Scholar
  25. 25.
    Shoenfeld Y, Gerli R, Doria A, Matsuura E, Cerinic MM, Ronda N et al (2005) Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation 112(21):3337–3347 (Nov 22)PubMedCrossRefGoogle Scholar
  26. 26.
    Farzaneh-Far A, Roman MJ (2005) Accelerated atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus. Int J Clin Pract 59(7):823–824 (Jul)PubMedCrossRefGoogle Scholar
  27. 27.
    Roman MJ, Shanker BA, Davis A, Lockshin MD, Sammaritano L, Simantov R et al (2003) Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med 349(25):2399–2406 (Dec 18)PubMedCrossRefGoogle Scholar
  28. 28.
    Blann AD (2000) Endothelial cell activation, injury, damage and dysfunction: separate entities or mutual terms?. Blood Coagul Fibrinolysis 11(7):623–630 (Oct)PubMedCrossRefGoogle Scholar
  29. 29.
    Sattar N, McCarey DW, Capell H, McInnes IB (2003) Explaining how “high-grade” systemic inflammation accelerates vascular risk in rheumatoid arthritis. Circulation 108(24):2957–2963 (Dec 16)PubMedCrossRefGoogle Scholar
  30. 30.
    Van Doornum S, McColl G, Wicks IP (2002) Accelerated atherosclerosis: an extraarticular feature of rheumatoid arthritis?. Arthritis Rheum 46(4):862–873 (Apr)PubMedCrossRefGoogle Scholar
  31. 31.
    Cronstein BN, Molad Y, Reibman J, Balakhane E, Levin RI, Weissmann G (1995) Colchicine alters the quantitative and qualitative display of selections on endothelial cells and neutrophils. J Clin Invest 96(2):994–1002 (Aug)PubMedCrossRefGoogle Scholar
  32. 32.
    Ben-Chetrit E, Bergmann S, Sood R (2006) Mechanism of the anti-inflammatory effect of colchicine in rheumatic diseases: a possible new outlook through microarray analysis. Rheumatol (Oxf) 45(3):274–282 (Mar)CrossRefGoogle Scholar
  33. 33.
    Ozcakar ZB, Yalcinkaya F, Yuksel S, Acar B, Gokmen D, Ekim M (2006) Possible effect of subclinical inflammation on daily life in familial Mediterranean fever. Clin Rheumatol 25(2):149–152 (Mar)PubMedCrossRefGoogle Scholar
  34. 34.
    Agewall S (2003) Is impaired flow-mediated dilatation of the brachial artery a cardiovascular risk factor?. Curr Vasc Pharmacol 1(2):107–109 (Jun)PubMedCrossRefGoogle Scholar
  35. 35.
    Berghoff M, Kathpal M, Khan F, Skinner M, Falk R, Freeman R (2003) Endothelial dysfunction precedes C-fiber abnormalities in primary (AL) amyloidosis. Annals of neurology 53(6):725–730 (Jun)PubMedCrossRefGoogle Scholar
  36. 36.
    Bozkurt AI, Sahinoz S, Ozcirpici B, Ozgur S, Sahinoz T, Acemoglu H et al (2006) Patterns of active and passive smoking, and associated factors, in the South-east Anatolian Project (SEAP) region in Turkey. BMC public health 6:15PubMedCrossRefGoogle Scholar

Copyright information

© Clinical Rheumatology 2007

Authors and Affiliations

  • Ismail Sari
    • 1
  • Oguzhan Karaoglu
    • 2
  • Gercek Can
    • 1
  • Servet Akar
    • 1
  • Aytac Gulcu
    • 2
  • Merih Birlik
    • 1
  • Nurullah Akkoc
    • 1
  • Mehmet Tunca
    • 3
  • Yigit Goktay
    • 2
  • Fatos Onen
    • 1
    • 4
  1. 1.Department of Internal Medicine, Division of Rheumatology, School of MedicineDokuz Eylul UniversityInciralti, IzmirTurkey
  2. 2.Department of Radiology, School of MedicineDokuz Eylul University Inciralti, IzmirTurkey
  3. 3.Department of Internal Medicine, School of MedicineDokuz Eylul UniversityInciralti, IzmirTurkey
  4. 4.Tip Fakultesi, Ic hastaliklari ABD, Immunoloji-Romatoloji BDDokuz Eylul UniversitesiInciralti, IzmirTurkey

Personalised recommendations