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Increased Asymmetric Dimethylarginine Levels in Young Men with Familial Mediterranean Fever (FMF): Is It Early Evidence of Interaction Between Inflammation and Endothelial Dysfunction in FMF?

HAKAN M. TEREKECI, CAGATAY OKTENLI, TANER OZGURTAS, SELIM NALBANT, CIHAN TOP, SERKAN CELIK, SERKAN TAPAN, YASAR KUCUKARDALI, YAVUZ S. SANISOGLU, EMRULLAH SOLMAZGUL, BURAK SAHAN, and OZKAN SAYAN

ABSTRACT.

Objective. Unlike in many other chronic inflammatory rheumatic diseases, studies investigating endothelial dysfunction and atherosclerosis in familial Mediterranean fever (FMF) are limited, and the results are controversial. Asymmetric dimethylarginine (ADMA) is considered an indicator for endothelial dysfunction and a sensitive marker for cardiovascular risk. There have been no reports on serum ADMA levels in patients with FMF.

Methods. We aimed (1) to determine serum ADMA concentrations in 38 young male patients with FMF and 23 age- and body mass index-matched healthy volunteers; (2) to evaluate its correlations with MEFV mutations, C-reactive protein (CRP) levels, and lipid profile; and (3) to compare effects of colchicine on circulating ADMA concentrations.

Results. In patients with FMF, ADMA and CRP levels were higher than in healthy controls. The mean levels of ADMA and CRP were higher during acute attacks than in attack-free periods. Patients taking colchicine had lower serum ADMA levels than non-colchicine users. There was a positive strong correlation between ADMA and CRP in patients with FMF. Stepwise linear regression analysis in patients with FMF revealed that age and CRP levels were independently associated with serum ADMA levels.

Conclusion. Our data imply that higher serum ADMA levels in FMF may indicate inflammation-related "endothelial dysfunction." It seems likely that regular use of colchicine is effective in preventing the development of and reversing not only amyloidosis but also endothelial dysfunction in patients with FMF. (J Rheumatol First Release Sept 1 2008)

Key Indexing Terms:

FAMILIAL MEDITERRANEAN FEVER
ASYMMETRIC DIMETHYLARGININE
C-REACTIVE PROTEIN
INFLAMMATION
ENDOTHELIAL DYSFUNCTION
COLCHICINE
PYRIN MUTATIONS

From the Division of Internal Medicine, GATA Haydarpasa Training Hospital, Istanbul; Department of Biochemistry, Gülhane Military Medical Academy; Department of Monitoring and Evaluation, Turkish Ministry of Health, Ankara; and Division of Hematology, GATA Haydarpasa Training Hospital, Istanbul, Turkey.

H.M. Terekeci, MD; C. Oktenli, MD, Division of Internal Medicine, GATA Haydarpasa Training Hospital; T. Ozgurtas, MD, Department of Biochemistry, Gülhane Military Medical Academy; S. Nalbant, MD; C. Top, MD; S. Celik, MD, Division of Internal Medicine, GATA Haydarpasa Training Hospital; S. Tapan, MD, Gülhane Military Medical Academy; Y. Kucukardali, MD, Division of Internal Medicine, GATA Haydarpasa Training Hospital; Y.S. Sanisoglu, PhD, Department of Monitoring and Evaluation, Turkish Ministry of Health; E. Solmazgul, MD; B. Sahan, MD, Division of Internal Medicine; O. Sayan, MD, Division of Hematology, GATA Haydarpasa Training Hospital.

Address reprint requests to Dr. H.M. Terekeci, GATA Haydarpasa Training Hospital, Division of Internal Medicine, Selimiye Mah, Tibbiye Cad, TR-34668 Kadikoy, Istanbul, Turkey. E-mail: mhterekeci@yahoo.com.tr or coktenli@yahoo.com

Accepted for publication May 27, 2008.