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Copyright © 2008 Society for Heart Attack Prevention and Eradication. All Rights Reserved.
Evaluation of intima media thickness of the common and internal carotid arteries with inflammatory markers in familial Mediterranean fever as possible predictors for
atherosclerosis
Yelda Bilginer1, Fatih Ozaltin1, Ceyla Basaran2, Ali Duzova1, Nesrin Besbas1, Rezan Topaloglu1, Seza Ozen1, Aysin Bakkaloglu1
Hacettepe University Faculty of Medicine1Dept.of Pediatric Nephrology
2Dept.of Radiology
Corresponding Author: Fatih Ozaltin, M.D.Hacettepe University Faculty of Medicine Dept.of Pediatric NephrologyAnkara / TurkeyE-mail: [email protected]
Copyright © 2008 Society for Heart Attack Prevention and Eradication. All Rights Reserved.
BACKGROUND
• Familial Mediterranean Fever (FMF) is an autosomal recessive disorder characterized by recurrent episodes of fever and serosal inflammation.
• Although FMF is a periodic disease recent data have suggested that a continuous subclinical inflammation is present.
• The long term effects of subclinical inflammation in FMF are not well evaluated.
Copyright © 2008 Society for Heart Attack Prevention and Eradication. All Rights Reserved.
BACKGROUND• Inflammation plays a major role in the process of atherosclerosis.
• Atherosclerotic structural changes begin before clinical findings.
• Intima media thickness (IMT) has beeen established as a clinically useful index for identifying early stage atherosclerosis.
• Intima media thickness can be detected by high-resolution B-mode ultrasonography, an easy, non-invasive and reliable method.
Salonen R, SalonenJT. Atherosclerosis 1990;81:33-40
Copyright © 2008 Society for Heart Attack Prevention and Eradication. All Rights Reserved.
AIMS
• To determine whether arterial wall thickening is advanced in FMF patients compared to healthy controls
• To evaluate the possible associations of clinical and laboratory features on IMT of carotid arteries.
Copyright © 2008 Society for Heart Attack Prevention and Eradication. All Rights Reserved.
PATIENTS AND METHODS-1
• 70 FMF patients
• 50 age, sex and body mass index matched controls
• Inclusion criteria Patients without cardiovascular disease Positive for homozygous or compound heterozygous disease causing
mutation in MEFV gene Attack free period Disease duration ≥ 3 years
• Laboratory studies Acute phase reactants (erythrocyte sedimentation rate (ESR),
C-reaktive protein (CRP), fibrinogen, serum amyloid A (SAA) Lipid profile Serum homocysteine level
Copyright © 2008 Society for Heart Attack Prevention and Eradication. All Rights Reserved.
PATIENTS AND METHODS-2B-Mode ultrasonography
B mode ultrasonography: Right common carotid artery demonstrating increased wall thickness
Copyright © 2008 Society for Heart Attack Prevention and Eradication. All Rights Reserved.
Clinical Characteristics of FMF patients and Control Group
Variable FMF patients
(n=70)
Controls
(n=50)
p*
Age (years) 14 (4-24) 14 (4-18) 0.93
Sex F/M 30/40 24/26 ND
Height SDS -0.72 1.03 -0.24 0.95 0.10
Body mass index (kg/m2) 21.91 4.11 21.55 2.63 0.32
Systolic BP (mmHg) 103.50 11.17 104.40 10.50 0.73
Systolic BP (Z score) 0.24 0.86 0.23 0.78 0.33
Diastolic BP (mmHg) 66.42 6.97 66.73 6.47 0.76
Diastolic BP (Z score) 0.37 0.57 0.33 0.29 0.35
Age at diagnosis (years) 5.00 4.03 -
Disease duration (years) 6.95 3.02 -
Treatment duration 5.75 3.52 -
ESR (mm/h) 19.01 3.8 7.96 3.86 0.03*
CRP (mg/dl) 0.79 0.41 0.4 0 0.02*
Fibrinogen (mg/dl) 345.2 45.5 284.2 27.09 0.01*
SAA (g/ml) 55.9 51.6 14 2.64 <0.001*
Cholesterol (mg/dl) 123.2 20.52 112.8 16.7 0.431
HDL-cholesterol (mg/dl) 53.29 17.9 43.4 8.48 0.029*
LDL-cholesterol (mg/dl) 70.23 14.4 67.5 12.7 0.435
Homocysteine (mol/l) 8.6 1.5 8.28 1.36 0.328
Copyright © 2008 Society for Heart Attack Prevention and Eradication. All Rights Reserved.
Intima Media Thickness (IMT) of
FMF Patients and Control Group
ControlsPatients
CC
A-I
MT
(m
m)
,7
,6
,5
,4
,3
,2
,1
p<0.001
ControlsPatients
ICA
-IM
T (
mm
)
,5
,4
,3
,2
,1
0,0
p<0.001
CCA Common Carotid Artery;
ICA Internal Carotid Artery
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Correlation between intima media thickness of the common carotid artery (CCA-IMT) and serum amyloid A (SAA) levels
Serum amyloid A (ug/ml)
3002001000
CC
A-I
MT
(m
m)
,7
,6
,5
,4
,3
,2
r=0.24, p=0.04
Copyright © 2008 Society for Heart Attack Prevention and Eradication. All Rights Reserved.
CONCLUSION
• Intima media thickness, an early predictor of atherosclerosis, is associated with subclinical inflammation in children with FMF
• Serum Amyloid A protein proved to correlate best with intimal thickness
• Our findings supports that a chronic modest increase in SAA level appears to be associated with an increased risk of cardiovascular disease