Assessment of aortic stiffness and ventricular functions in familial Mediterranean fever/Ailevi Akdeniz atesinde aortik sertlesme parametrelerinin ve ventrikul fonksiyonlarinin degerlendirilmesi.

Dear Editor,

Familial Mediterranean fever (FMF) is an autosomal recessive disorder virtually restricted to certain ethnic groups originating from the Middle East: Sephardic Jews, Armenians, Arabs, Druze and Turks (1). It is characterized by recurrent episodes of serosal inflammation, chest pain, and arthritis usually accompanied by fever (1). The main complication of untreated patients is the development of amyloidosis (1). In most FMF patients, colchicine treatment prevents febrile attacks and development of amyloidosis. During the febrile attacks, an acute phase response develop, manifested by a marked increase in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum amyloid A, fibrinogen and leucocytes (1). Histopathologic examination of FMF involves inflammation with infiltration by neutrophils (1). Systemic inflammation is an important factor in the initiation or the progression of atherosclerosis. Damage to the arterial wall due to inflammation and atherosclerosis causes decreased arterial distensibility, compliance and elasticity (2-4). Non--invasive ultrasound teniques are used to evaluate vascular system and cardiovascular condition (3, 4). One such technique, Doppler pulse wave velocity (PWV), which is defined as arterial pulse's velocity of moving along vessel wall, as an indicator of arterial elasticity (2-4). Pulse wave velocity is inversely correlated with arterial distensibility and relative arterial compliance. Inflammation may play a role in the process of arterial stiffening (3, 4).

We read with interest the article "Assessment of aortic stiffness and ventricular functions in familial Mediterranean fever" by Sari et al. (5) which compared the aortic stiffness and ventricular functions in patients with FMF and control group. The authors have reported the aortic wall properties were similar between two groups, however, we have recently showed that the carotid-femoral PWV was slightly higher in colchicine-treated FMF patients than in control subjects (p=0.05) (4). We also found significant correlation between PWV and age (p<0.001, r=0.67), body mass index (p<0.001, r=0.52) and leucocytes (p<0.001, r=0.66) in all groups and in patients with FMF group (p<0.001, r=0.73; p=0.01, r=0.52; p<0.001, r=0.69, respectively) (4). The inflammatory process of FMF may act to impair endothelial function, arterial compliance and arterial elasticity and as a contributing factor in the initiation or the progression of atherosclerosis. In the light of these findings, we think that Sari et al. should detail why the aortic elastic properties and pericardium showed no significant difference between patients with FMF group and healthy controls groups.

Mustafa Yildiz, Murat Biteker, Mehmet Ozkan

Kartal Kosuyolu Heart Education and Research Hospital, Cardiology, Istanbul, Turkey

References

(1.) Sohar E, Gafni J, Pras M, Heller H. Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med 1967; 43: 227-53.

(2.) Yildiz M, Sahin B, Sahin A. Acute effects of oral melatonin administration on arterial distensibility, as determined by carotid-femoral pulse wave velocity, in healthy young men. Exp Clin Cardol 2006; 11: 311-3.

(3.) Yildiz M, Soy M, Kurum T, Yildiz BS. Arterial distensibility in Wegener's granulomatosis: a carotid-femoral pulse wave velocity study. Anadolu Kardiyol Derg 2007; 7: 281-5.

(4.) Yildiz M, Masatlioglu S, Seymen P, Aytac E, Sahin B, Seymen HO. The carotid-femoral (aortic) pulse wave velocity as a marker of arterial stiffness in familial Mediterranean fever. Can J Cardiol 2006; 22: 1127-31.

(5.) Sari I, Arican O, Can G, Akdeniz B, Akar S, Birlik M, et al. Assessment of aortic stiffness and ventricular functions in familial Mediterranean fever. Anadolu Kardiyol Derg 2008; 8: 271-8.

Address for Correspondence/Yazisma Adresi: Dr. Murat Biteker, Kartal Kosuyolu Heart Education and Research Hospital, Cardiology, Istanbul, Turkey Phone: [phone] Fax: [phone] E-posta: [e-mail]

Author's Reply

Dear Sir,

We thank authors for their interest and valuable comments on our recent publication (1).

Familial Mediterranean fever (FMF) is an auto inflammatory rheumatic disease characterized by periodic attacks of fever and serositis. During the attack free periods, subclinical inflammation continues (2). In recent years markers of increased early atherosclerosis have been reported in various inflammatory rheumatic diseases including FMF (1). On the other hand, increase in aortic stiffness is a manifestation of vascular damage and predictor of cardiovascular mortality. Thus, measurement of arterial stiffness became an important part of risk assessment and monitoring the efficacy of therapy in patients with conditions such as isolated systolic hypertension (3). At present, there are several methods available that can be used to analyze arterial elasticity. Although invasive methods remain gold standard, noninvasive techniques are widely used in clinical settings as these methods give us safe and accurate means of detecting of arterial elasticity. Among them, pulse pressure, pulse wave velocity, ultrasound derived indices, waveform analysis and magnetic resonance imaging derived indices are the most commonly used and popular methods (4, 5).

The study by Yildiz et al. used carotid and femoral Doppler pulse wave velocity (PWV) and in the present study, we estimated aortic distensibility from echocardiographic measurements of aortic diameter at systole and diastole, and aortic pressure was assessed by brachial cuff blood pressure taken at the time when echocardiographic measurements were made. This method enables us to estimate the elastic properties of the ascending aorta from its direct measurements. Although carotid and femoral PWV requires little technical expertise and used widely, ultrasound derived methods are also reliable and used in clinical settings extensively (6, 7).

The former study by Yildiz et al included 23 FMF patients and controls and according to their results, although missed significance, PWV was slightly higher in FMF group (8). In contrast, our results were not different between patients and controls. Although both groups had similar age ratios and body composition parameters (Table 1), mainly two important factors might be responsible from this situation: 1--methodological differences may be accounted from the condition, and 2--as figured out from the high mean C--reactive protein values in the group of patients studied by Yildiz et al., higher inflammatory burden might affect the results.

In conclusion, further studies comprising new promising techniques such as MRI and studies including active and inactive FMF patients are needed to determine whether aortic stiffness in FMF is increased or not.

Ismail Sari, Fatos Onen

Department of Rheumatology, Dokuz Eylul University School of Medicine, Izmir, Turkey

References

(1.) Sari I, Arican 0, Can G, Akdeniz B, Akar S, Birlik M, et al. Assessment of aortic stiffness and ventricular functions in familial Mediterranean fever. Anadolu Kardiyol Derg 2008; 8: 271-8.

(2.) Onen F. Familial Mediterranean fever. Rheumatol Int 2006; 26: 489-96.3. Boutouyrie P, Laurent S, Briet M. Importance of arterial stiffness as cardiovascular risk factor for future development of new type of drugs. Fundam Clin Pharmacol 2008; 22: 241-6.

(4.) Mackenzie IS, Wilkinson IB, Cockcroft JR. Assessment of arterial stiffness in clinical practice. QJM 2002; 95: 67-74.

(5.) Boutouyrie P. New techniques for assessing arterial stiffness. Diabetes Metab. 2008;34 Suppl 1: S21-6.

(6.) Marcus RH, Korcarz C, McCray G, Neumann A, Murphy M, Borow K, et al. Noninvasive method for determination of arterial compliance using Doppler echocardiography and subclavian pulse tracings. Validation and clinical application of a physiological model of the circulation. Circulation 1994; 89: 2688-99.

(7.) Stefanadis C, Stratos C, Boudoulas H, Kourouklis C, Toutouzas P. Distensibility of the ascending aorta: comparison of invasive and noninvasive techniques in healthy men and in men with coronary artery disease. Eur Heart J 1990; 11: 990-6.

(8.) Yildiz M, Masatlioglu S, Seymen P, Aytac E, Sahin B, Seymen HO. The carotid-femoral (aortic) pulse wave velocity as a marker of arterial stiffness in familial Mediterranean fever. Can J Cardiol 2006; 22: 1127-31.

Yazisma Adresi/Address for Correspondence: Ismail Sari, MD, Dokuz Eylul Universty Scool of Medicine, Department of Internal Medicine, Divison of Rheumatology

Phone: [phone] Fax: [phone] E-mail: [e-mail]

Table 1. Some demographical and laboratory findings of studies
conducted by Sari et al (1) and Yildiz et al (8)

                            Study by San et al.

                           FMF              Controls

Number of subjects          44                 27

Sex, M/F                  21/23              12/15

Age, years           32.6[+ or -]9.2    30.9[+ or -]4.7

BMI, kg/[m.sup.2]    24.7[+ or -]4.1    24.5[+ or -]3.8

WHR                  0.84[+ or -]0.08   0.82[+ or -]0.09

Mean blood           88.7[+ or -]8.9    90.8[+ or -]6.8
Pressure, mm/Hg

Fasting glucose,     85.4[+ or -]6.1    83.3[+ or -]7.4
mg/dL

Total cholesterol,   162[+ or -]31.8    170[+ or -]30.2
mg/dL

LDL cholesterol,      92[+ or -]29.6     95[+ or -]25.4
mg/dL

HDL cholesterol,     50.3[+ or -]10.8   56.4[+ or -]14.5
mg/dL

Triglyceride,        108[+ or -]43.3     90[+ or -]35.8
mg/dL

ESR, mm/h            17.7[+ or -]17.9    8.9[+ or -]5.3

CRP, mg/dL           0.67[+ or -]1.23   0.17[+ or -]0.21

                             Study by Yildiz et al.

                           FMF               Controls

Number of subjects          23                  23

Sex, M/F                   6/17                6/17

Age, years             29.4[+ or -]8.7     29.2[+ or -]9

BMI, kg/[m.sup.2]     23.29[+ or -]3.53   23.47[+ or -]4.1

WHR                        0.82                0.80

Mean blood            77.75[+ or -]9.26   81.87[+ or -]7.98
Pressure, mm/Hg

Fasting glucose,            --                  --
mg/dL

Total cholesterol,   166.86[+ or -]36.6    163[+ or -]27.38
mg/dL

LDL cholesterol,     103.73[+ or -]26.9   90.85[+ or -]26.02
mg/dL

HDL cholesterol,            --                   --
mg/dL

Triglyceride,         99.3[+ or -]39.19    100[+ or -]28.17
mg/dL

ESR, mm/h            16.65[+ or -]11.97   10.00[+ or -]1.63

CRP, mg/dL            1.35[+ or -]2.26     0.27[+ or -]0.11

BMI--body mass index, CRP--C-reactive protein, ESR--erythrocyte
sedimentation rate, F-female, HDL--high density lipoprotein,
LDL--low density lipoprotein, WHR--waist-hip ratio, M-male