Endothelial dysfunction and subclinical atherosclerosis as ...0.50 mm in 10 persons, 0.54 mm in nine persons, and 0.56 mm in seven persons Figs. 2c, 3c and 4c Table 4. Fig. 1b The

The Egyptian Journal of Radiology and Nuclear Medicine (2013) 44, 237–243

Egyptian Society of Radiology and Nuclear Medicine

The Egyptian Journal of Radiology andNuclearMedicine

www.elsevier.com/locate/ejrnmwww.sciencedirect.com

ORIGINAL ARTICLE

Endothelial dysfunction and subclinical atherosclerosisas evidenced by the measurement of flow mediateddilatation of brachial artery and carotid intimamedia thickness in patients with rheumatoid arthritis

Noha Mohamed AbdelMaboud *, Hytham Haroon Elsaid 1

Lecturer of Radiodiagnosis, Department of Radiology, College of Medicine, Tanta University, Egypt

Received 18 September 2012; accepted 24 December 2012Available online 6 February 2013

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KEYWORDS

Rheumatoid arthritis;

Endothelial dysfunction;

Brachial artery flow medi-

ated dilatation;

Carotid intima media

thickness

bbreviations: RA, rheumatoid

D, flow mediated dilatati

tima media thickness; ED, en

Corresponding author. Addr

harbeya, Egypt. Tel.: +20 10mail addresses: hythamharoo

[email protected] (H

Address: Tanta University H

20 1223658711.

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uclear Medicine.

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Abstract Aim of the work: The present study aimed at evaluating the prevalence of subclinical

atherosclerosis and cardiovascular disease by means of assessment of carotid intima media thick-

ness and endothelium dependent function through assessment of brachial artery flow mediated

dilatation in patients with rheumatoid arthritis.

Materials and methods: Twenty six patients with rheumatoid arthritis and 20 healthy control

subjects underwent measurement of brachial artery FMD and CIMT using B-mode gray scale

US for evaluating cardiovascular risk.

Results: The brachial artery FMD was –96.6–6.6% in rheumatoid arthritis (indicating ED), and

20–25% in the control group. The CIMT was 0.50–0.72 mm in rheumatoid arthritis and

0.35–0.47 mm in the control group.

Conclusion: The results from the present study support the use of carotid US and endothelial func-

tion assessment by means of FMD as a useful tool to predict the increased risk of cardiovascular

CVD, cardiovascular disease;

nitric oxide; CIMT, carotid

l dysfunction.

a University Hospital, Tanta,

5.o.com (N.M. AbdelMaboud),

id).

Tanta, Gharbeya, Egypt. Tel.:

tian Society of Radiology and

g by Elsevier

Radiology and Nuclear Medicine. Production and hosting by Elsevier B.V. All rights reserved.

p://dx.doi.org/10.1016/j.ejrnm.2012.12.009

mailto:[email protected]:[email protected]://dx.doi.org/10.1016/j.ejrnm.2012.12.009http://www.sciencedirect.com/science/journal/0378603Xhttp://creativecommons.org/licenses/by-nc-nd/4.0/

Table 1 The brachial artery diamet

group.

Number D1 (mm) D

5 2.5 3

7 3 3

8 3.2 4

Fig. 1a T

238 N.M. AbdelMaboud, H.H. Elsaid

disease in patients with rheumatoid arthritis. We suggest that the carotid artery US should be per-

formed for all patients with rheumatoid arthritis to establish the risk of cardiovascular complication

which requires more aggressive therapy.

� 2013 Egyptian Society of Radiology and Nuclear Medicine. Production and hosting by Elsevier B.V.Open access under CC BY-NC-ND license.

1. Introduction

Rheumatoid arthritis (RA) is the most common systemic auto-immune disease. Patients with rheumatoid arthritis are at in-creased risk for cardiovascular diseases (CVD), one of theearliest manifestations of CVD is endothelial dysfunction(ED)

(1). The endothelium is the innermost lining of the vasculatureand is responsible for maintaining vascular homeostasis via thebalanced production of a number of vasoactive factors such as

nitric oxide (NO) which play an important role in vasodilata-tion and inhibiting the atherosclerotic process (2). Damage tothe endothelium can reduce (NO) activity, causing endothelial

dysfunction which is an early indicator of CVD (3). ED is animportant sign of early atherosclerosis and can be assessednon invasively by the impairment of endothelial dependantflow mediated vasodilatation (ED-FMD) of peripheral arteries

measured by US (4). Increased carotid intima –media thickness(CIMT), measured by US, is also regarded as an early indica-tor of atherosclerosis and future CVD (5).

2. Patients and methods

2.1. Patients and control

The subjects in the present study were 26 RA patients (23 fe-

males and 3 males), and 20 healthy control subjects.All patients have the following criteria: ages between 35 and

60 years, non tobacco users, did not present other autoimmune

diseases, hypertension, diabetes mellitus, dyslipidemia, renal

er and FMD in the control

2 (mm) FMD (%)

20

.7 23.3

25

he basal diameter of the brachia

insufficiency or received drugs affecting the cardiovascularsystem.

20 healthy volunteers were recruited as control .Writtenconsent was taken from all patients and the control groupand the institutional ethics committee approved the study

protocol.

2.2. Methods: Radiological assessment by US

2.2.1. Carotid US

The subject was made to lie supine with slight hyperextensionof the neck .Both common carotid arteries were examined

using a 7 MHz linear array transducer in a PHILIPS HD11instrument. Carotid intima –media thickness and lumen diam-eter were measured from end diastolic M-mode images (mini-

mum distension) of the wall of the distal common carotidartery in a location not containing plaque. The greater distancebetween lumen – intima and media-adventitia interface was

measured. The mean value of the two sides was taken.

2.3. Flow mediated vasodilatation of brachial artery

The procedure was performed on the same US machine andthe same transducer as used in carotid US.

The subject lies in a supine position; the right brachial ar-tery was scanned in longitudinal section 2–15 cm. above the

antecubital fossa with B-mode. The clearest picture of the ar-tery at the center was obtained (the transducer was kept con-stant throughout the procedure by noting the relation of the

artery with the adjacent anatomical landmarks).The luminaldiameter of the artery was measured by calculating the dis-tance between the proximal and distal intima. Ischemia was in-

duced with a sphygmomanometer cuff placed around theforearm distal to the scanned region inflated to 200 mmHGfor 4 min and then released. A second scan was taken at thisstage and the luminal diameter was measured 60 s. after cuff

deflation .The endothelium dependant function is defined bythe formula: D2-D1/D1x100 the higher the numeric value ofthe study , the better the endothelial function. ED is considered

when the FMD is

Fig. 1b The post- occlusion diameter of brachial artery in the same person = 4 mm, FMD 25% denoting good endothelial function.

Fig. 1c The carotid intima media thickness 0.44 mm.

Table 2 The brachial artery diameter and FMD in the

rheumatoid arthritis patients.

Number D1 (mm) D2 (mm) FMD (%)

10 4.3 4.3 0

8 4.1 4.3 4.8

3 3 3.2 6.6

5 3 3.4 �96.6

Fig. 2a The basal diameter of the brachial artery i

Endothelial dysfunction and subclinical atherosclerosisas evidenced by the measurement of flow mediated 239

3. Results

This study included 26 patients of rheumatoid arthritis with anage range of 35–60 years and 20 healthy control subjects with

the same age range.Table 1 shows the characteristics of the study group in

which the diameter of the brachial artery before the induction

of ischemia (D1) was 2.5 mm in five subjects, after the releaseof ischemia (D2) 3 mm, the FMD was 20%.D1was 3 mm in se-ven subjects, D2 was 3.7 mm and FMD was 23.3%.D1 was 3.2

in eight subjects, D2 was 4 mm and the FMD was 25% Fig. 1aand b.

Table 2 shows the characteristics of the rheumatoid arthri-

tis group in which the diameter of the brachial artery beforethe induction of ischemia (D1) was 4.3 mm in 10 subjects, afterthe release of ischemia (D2) 4.3 mm, the FMD was 0% D1 was4.1 mm in eight subjects, D2 was 4.3 mm and FMD was 4.8%.

D1 was 3 in three subjects, D2 was 3.2 mm and the FMD was6.6%. D1 was 3 in five subjects, D2 was 3.4 mm and the FMDwas –96.6% Figs. 2a and b, 3a and b, 4a and b.

So, the higher the numeric value of the FMD, the better theendothelial function.

The CIMT in the control group was 0.44 mm in eight per-

sons, 0.47 mm in nine persons, and 0.35 mm in three personsFig. 1c Table 3.

The CIMT in the rheumatoid arthritis patients was

0.50 mm in 10 persons, 0.54 mm in nine persons, and0.56 mm in seven persons Figs. 2c, 3c and 4c Table 4.

n a patient with rheumatoid arthritis = 4.3 mm.

Fig. 2b The post- occlusion diameter of brachial artery in the same person = 4.3 mm, FMD 0% denoting poor endothelial function.

Fig. 2c The carotid intima media thickness in the same person

0.72 mm.


4. Discussion

Rheumatoid arthritis is associated with excessive cardiovascu-lar mortality [6]. Almost half of all deaths in rheumatoidarthritis results from cardiovascular causes (7). Therefore, it

may be suggested that the main cause of mortality and morbid-ity is ischemic heart disease in patients with RA (7). Discovery

Fig. 3a The basal diameter of brachial artery in

of early interventions in RA disease that might influence ath-erosclerotic progression are essentials to determine approachesthat could in turn reduce the subsequent risk of cardiovascularmortality (8,9). CIMT is a known strong predictor of cardio-

vascular events in the general population (10), and has beenpredominantly reported in the literature on patients with RA(11). The results from our study show that the CIMT has a

high predictive value for the development of CVD. Our resultswere the same as Gonzalez–Juanatey C et al. (12) in which thepresence of subclinical atherosclerosis, manifested by increased

value of CIMT is consistent with the high rate of silent ische-mic heart diseases and sudden cardiac death observed in RApatients. Van Sijl AM et al (13) proved in their study thatCIMT is frequently used to identify the population at elevated

cardiovascular risk. (17) The results of our study implicate thatthe mean CIMT of the common carotid artery was signifi-cantly higher in RA patients than in healthy subjects. Van Sijl

AM etal (13), found that the CIMT difference between RA pa-tients and the control subject may be very small as inHigginsJP et al. (14) and other studies such as Kumeda Y et al. (15)

& Mahajan V et al. (16) found a greater difference. Finally,Van Sijl AM etal (13) stated that the variation in ultrasoundprotocols for determining CIMT between all studies is an

important observation but also complicates the interpretationof the individual study results. Still, they think that the differ-ences in ultrasound protocols or in other methodological as-pects are unlikely to have caused a systematic bias toward

under - or overestimation of CIMT difference between RA pa-tients and control. So, US scanning of CIMT has been shownto be an accurate method for estimating cardiovascular risk

a patient with rheumatoid arthritis = 4.1 mm.

Fig. 3b The post- occlusion diameter of brachial artery in the same person = 4.3 mm, FMD 4.8% denoting poor endothelial function.


0.64 mm.


(17). RA appears to be associated with accelerated atheroscle-rosis, the mechanisms involved are not clear, but may includeendothelial dysfunction mediated by systemic inflammation(18). Our study demonstrates that patients with RA can also

present endothelial dysfunction which may be the earliest event

Fig. 4a The basal diameter of brachial artery in

in the atheromatous lesion, so its evaluation is a promisingtool for the estimation of coronary affection. Castro PT

et al. (19) study mentioned that FMD allows an adequate eval-uation of endothelial behavior and reflects the coronary endo-thelial function and behavior inspite of that the ideal methodfor diagnosing endothelial dysfunction has not been estab-

lished yet. Our study coincides with those of Schroeder Set al. (20) in which the age of the patient does not affect theendothelial function evaluation with FMD. We have found

no significant difference in the different age groups of patientsand the control group regarding the FMD .Like the presentstudy, other studies like Hurlimann D et al. (21) have found

a significant endothelial dysfunction in patients with autoim-mune disease like RA by means of FMD .The presence of sys-temic inflammation predisposes to atherosclerosis, affectingthe endothelial function and decreasing the production of ni-

tric oxide by the endothelium, this decrease in the nitric oxideproduction leads to a smaller arterial dilatation upon inducedischemia. Quyyumi AA (22) affirms that systemic inflamma-

tion markers like FMD, CIMT and pulse wave analysis ariseas a method for evaluating the atherosclerosis risk .He recom-mends the inclusion of these methods in randomized study for

screening and diagnosis of cardiovascular risk. Consideringthat a high level of systemic inflammation affects the endothe-lial function, inflammation markers like FMD may provide a

better evaluation for the cardiovascular risk in patients withRA (23). In our study, we demonstrate that the FMD and

a patient with rheumatoid arthritis = 3 mm.

Fig. 4b The post-occlusion diameter of brachial artery in the same person = 3.2 mm, FMD 6.6% denoting poor endothelial function.

Table 3 CIMT in the control group.

Number CIMT (mm)

8 0.44

9 0.47

3 0.35

Table 4 CIMT in the rheumatoid arthritis patients.

Number CIMT (mm)

10 0.50

9 0.54

7 0.56


0.50 mm.


CIMT are promising methods for the evaluation of RA andare very helpful for the prevention of vascular risk.

5. Conclusion

The results from the present study support the use of carotid

US and endothelial function assessment by means of FMDas a useful tool to predict the increased risk of cardiovasculrdisease in patient with rheumatoid arthritis. We suggest that

the carotid artery US should be performed for all patients withrheumatoid arthritis to establish the risk of cardiovascularcomplication which requires more aggressive therapy.

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Endothelial dysfunction and subclinical atherosclerosis as evidenced by the measurement of flow mediated dilatation of brachial artery and carotid intima media thickness in patients with rheumatoid arthr1 Introduction2 Patients and methods2.1 Patients and control2.2 Methods: Radiological assessment by US2.2.1 Carotid US

2.3 Flow mediated vasodilatation of brachial artery

3 Results4 Discussion5 ConclusionReferences

Documents

Endothelial dysfunction and subclinical atherosclerosis as ...0.50 mm in 10 persons, 0.54 mm in nine persons, and 0.56 mm in seven persons Figs. 2c, 3c and 4c Table 4. Fig. 1b The