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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 arthritis
The Egyptian Journal of Radiology and Nuclear Medicine (2013) 44, 237–243
Egyptian Society of Radiology and Nuclear Medicine
The Egyptian Journal of Radiology and Nuclear Medicine www.elsevier.com/locate/ejrnm www.sciencedirect.com
ORIGINAL ARTICLE
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 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 2012 Available online 6 February 2013
KEYWORDS Rheumatoid arthritis; Endothelial dysfunction; Brachial artery flow mediated dilatation; Carotid intima media thickness
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 thickness 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 function assessment by means of FMD as a useful tool to predict the increased risk of cardiovascular
Abbreviations: RA, rheumatoid arthritis; CVD, cardiovascular disease; FMD, flow mediated dilatation; NO, nitric oxide; CIMT, carotid intima media thickness; ED, endothelial dysfunction. * Corresponding author. Address: Tanta University Hospital, Tanta, Gharbeya, Egypt. Tel.: +20 1068643995. E-mail addresses: [email protected] (N.M. AbdelMaboud), [email protected] (H.H. Elsaid). 1 Address: Tanta University Hospital, Tanta, Gharbeya, Egypt. Tel.: +20 1223658711. Peer review under responsibility of Egyptian Society of Radiology and Nuclear Medicine.
Production and hosting by Elsevier 0378-603X Ó 2013 Egyptian Society of Radiology and Nuclear Medicine. Production and hosting by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ejrnm.2012.12.009
238
N.M. AbdelMaboud, H.H. Elsaid disease in patients with rheumatoid arthritis. We suggest that the carotid artery US should be performed for all patients with rheumatoid arthritis to establish the risk of cardiovascular complication which requires more aggressive therapy. Ó 2013 Egyptian Society of Radiology and Nuclear Medicine. Production and hosting by Elsevier B.V. All rights reserved.
1. Introduction Rheumatoid arthritis (RA) is the most common systemic autoimmune disease. Patients with rheumatoid arthritis are at increased risk for cardiovascular diseases (CVD), one of the earliest manifestations of CVD is endothelial dysfunction(ED) (1). The endothelium is the innermost lining of the vasculature and is responsible for maintaining vascular homeostasis via the balanced production of a number of vasoactive factors such as nitric oxide (NO) which play an important role in vasodilatation and inhibiting the atherosclerotic process (2). Damage to the endothelium can reduce (NO) activity, causing endothelial dysfunction which is an early indicator of CVD (3). ED is an important sign of early atherosclerosis and can be assessed non invasively by the impairment of endothelial dependant flow 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 indicator of atherosclerosis and future CVD (5).
insufficiency or received drugs affecting the cardiovascular system. 20 healthy volunteers were recruited as control .Written consent was taken from all patients and the control group and 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 hyperextension of the neck .Both common carotid arteries were examined using a 7 MHz linear array transducer in a PHILIPS HD11 instrument. Carotid intima –media thickness and lumen diameter were measured from end diastolic M-mode images (minimum distension) of the wall of the distal common carotid artery in a location not containing plaque. The greater distance between lumen – intima and media-adventitia interface was measured. The mean value of the two sides was taken.
2. Patients and methods
2.3. Flow mediated vasodilatation of brachial artery
2.1. Patients and control
The procedure was performed on the same US machine and the same transducer as used in carotid US. The subject lies in a supine position; the right brachial artery was scanned in longitudinal section 2–15 cm. above the antecubital fossa with B-mode. The clearest picture of the artery at the center was obtained (the transducer was kept constant throughout the procedure by noting the relation of the artery with the adjacent anatomical landmarks).The luminal diameter of the artery was measured by calculating the distance between the proximal and distal intima. Ischemia was induced with a sphygmomanometer cuff placed around the forearm distal to the scanned region inflated to 200 mmHG for 4 min and then released. A second scan was taken at this stage and the luminal diameter was measured 60 s. after cuff deflation .The endothelium dependant function is defined by the formula: D2-D1/D1x100 the higher the numeric value of the study , the better the endothelial function. ED is considered when the FMD is <4.55
The subjects in the present study were 26 RA patients (23 females 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
Table 1 group.
The brachial artery diameter and FMD in the control
Number
D1 (mm)
D2 (mm)
FMD (%)
5 7 8
2.5 3 3.2
3 3.7 4
20 23.3 25
Fig. 1a
The basal diameter of the brachial artery in a normal subject = 3.2 mm.
Endothelial dysfunction and subclinical atherosclerosisas evidenced by the measurement of flow mediated
Fig. 1b
239
The post- occlusion diameter of brachial artery in the same person = 4 mm, FMD 25% denoting good endothelial function.
3. Results
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)
10 8 3 5
4.3 4.1 3 3
4.3 4.3 3.2 3.4
Fig. 2a
FMD (%) 0 4.8 6.6 96.6
This study included 26 patients of rheumatoid arthritis with an age 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 release of ischemia (D2) 3 mm, the FMD was 20%.D1was 3 mm in seven 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. 1a and b. Table 2 shows the characteristics of the rheumatoid arthritis group in which the diameter of the brachial artery before the induction of ischemia (D1) was 4.3 mm in 10 subjects, after the release of ischemia (D2) 4.3 mm, the FMD was 0% D1 was 4.1 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 was 6.6%. D1 was 3 in five subjects, D2 was 3.4 mm and the FMD was –96.6% Figs. 2a and b, 3a and b, 4a and b. So, the higher the numeric value of the FMD, the better the endothelial function. The CIMT in the control group was 0.44 mm in eight persons, 0.47 mm in nine persons, and 0.35 mm in three persons Fig. 1c Table 3. The CIMT in the rheumatoid arthritis patients was 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.
The basal diameter of the brachial artery in a patient with rheumatoid arthritis = 4.3 mm.
240
Fig. 2b
N.M. AbdelMaboud, H.H. Elsaid
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 cardiovascular mortality [6]. Almost half of all deaths in rheumatoid arthritis results from cardiovascular causes (7). Therefore, it may be suggested that the main cause of mortality and morbidity is ischemic heart disease in patients with RA (7). Discovery
Fig. 3a
of early interventions in RA disease that might influence atherosclerotic progression are essentials to determine approaches that could in turn reduce the subsequent risk of cardiovascular mortality (8,9). CIMT is a known strong predictor of cardiovascular events in the general population (10), and has been predominantly 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 results were the same as Gonzalez–Juanatey C et al. (12) in which the presence of subclinical atherosclerosis, manifested by increased value of CIMT is consistent with the high rate of silent ischemic heart diseases and sudden cardiac death observed in RA patients. Van Sijl AM et al (13) proved in their study that CIMT is frequently used to identify the population at elevated cardiovascular risk. (17) The results of our study implicate that the mean CIMT of the common carotid artery was significantly higher in RA patients than in healthy subjects. Van Sijl AM etal (13), found that the CIMT difference between RA patients and the control subject may be very small as inHiggins JP 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 ultrasound protocols for determining CIMT between all studies is an important observation but also complicates the interpretation of the individual study results. Still, they think that the differences in ultrasound protocols or in other methodological aspects are unlikely to have caused a systematic bias toward under - or overestimation of CIMT difference between RA patients and control. So, US scanning of CIMT has been shown to be an accurate method for estimating cardiovascular risk
The basal diameter of brachial artery in a patient with rheumatoid arthritis = 4.1 mm.
Endothelial dysfunction and subclinical atherosclerosisas evidenced by the measurement of flow mediated
Fig. 3b
241
The post- occlusion diameter of brachial artery in the same person = 4.3 mm, FMD 4.8% denoting poor endothelial function.
Fig. 3c The carotid intima media thickness in the same person 0.64 mm.
(17). RA appears to be associated with accelerated atherosclerosis, the mechanisms involved are not clear, but may include endothelial 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
in the atheromatous lesion, so its evaluation is a promising tool for the estimation of coronary affection. Castro PT et al. (19) study mentioned that FMD allows an adequate evaluation of endothelial behavior and reflects the coronary endothelial function and behavior inspite of that the ideal method for diagnosing endothelial dysfunction has not been established yet. Our study coincides with those of Schroeder S et al. (20) in which the age of the patient does not affect the endothelial function evaluation with FMD. We have found no significant difference in the different age groups of patients and the control group regarding the FMD .Like the present study, other studies like Hurlimann D et al. (21) have found a significant endothelial dysfunction in patients with autoimmune disease like RA by means of FMD .The presence of systemic inflammation predisposes to atherosclerosis, affecting the endothelial function and decreasing the production of nitric oxide by the endothelium, this decrease in the nitric oxide production leads to a smaller arterial dilatation upon induced ischemia. Quyyumi AA (22) affirms that systemic inflammation markers like FMD, CIMT and pulse wave analysis arise as a method for evaluating the atherosclerosis risk .He recommends the inclusion of these methods in randomized study for screening and diagnosis of cardiovascular risk. Considering that a high level of systemic inflammation affects the endothelial function, inflammation markers like FMD may provide a better evaluation for the cardiovascular risk in patients with RA (23). In our study, we demonstrate that the FMD and
The basal diameter of brachial artery in a patient with rheumatoid arthritis = 3 mm.
242
Fig. 4b
N.M. AbdelMaboud, H.H. Elsaid
The post-occlusion diameter of brachial artery in the same person = 3.2 mm, FMD 6.6% denoting poor endothelial function.
5. Conclusion The results from the present study support the use of carotid US and endothelial function assessment by means of FMD as a useful tool to predict the increased risk of cardiovasculr disease in patient with rheumatoid arthritis. We suggest that the carotid artery US should be performed for all patients with rheumatoid arthritis to establish the risk of cardiovascular complication which requires more aggressive therapy. References
Fig. 4c The carotid intima media thickness in the same person 0.50 mm.
Table 3
CIMT in the control group.
Number
CIMT (mm)
8 9 3
0.44 0.47 0.35
Table 4
CIMT in the rheumatoid arthritis patients.
Number
CIMT (mm)
10 9 7
0.50 0.54 0.56
CIMT are promising methods for the evaluation of RA and are very helpful for the prevention of vascular risk.
(1) Sandool A, Carroll D, Metsios GS, Kitas GD, Zanten VV. The association between microvascular and macrovascular endothelial function in patients with rheumatoid arthritis. Arthritis Res Ther 2011:13. (2) Ahluwalia A, Foster P, Scotland RS, Mclean PG, Mathur A, Perretti M, et al. Antiinflammatory activity of soluble guanylate cyclase: Cgmp-dependent down–regulation of P-selection expression and leukocyte recruitment. Proc Natl Aead Sci USA 2004;101:1386–91. (3) Lerman A, Zeiher AM. Endothelial function: cardiac events. Circulation 2005;111:363–8. (4) Gonzalez-Juanatey C, Llorca J, Martin J, Gonzalez –Gay MA. Carotid intima–media thickness predicts the development of cardiovascular events in patients with rheumatoid arthritis. Semin Arthritis Rheum 2009;38:366–71. (5) Adhikari MC, Guin A, Chakraborty S, Sinhamahapatra P, Ghosh A. Subcilinical atherosclerosis and endothelial dysfunction in patients with early rheumatoid arthritis as evidenced by measurement of carotid intima media thickness and flow mediated vasodilatation: an observational study. Elsevier; 2011. (6) Vaudo G, Marchesi S, Gerli R, Allegrucci R, Giordano A, Siepi D, et al. Endothelial dysfunction in young patients with rheumatoid arthritis and low disease activity. Ann Rheum Dis 2004;63:31–5. (7) Castro PT, Montenegro CA, Carvalho ACP, Filho JF, Bianchi W, Bianchi DV, et al. Brachial artery flow–mediated dilatation in women with rheumatoid arthritis. Radiol Bras 2007;40:4. (8) Hannawi S, Marwick TH, Thomas R. Inflammation predicts accelerated brachial arterial wall changes in patients with recentonset rheumatoid arthritis. Arthritis Res Ther 2009;11(2):R51. (9) Del Rincon ID, Williams K, Stern MP, Freeman GL, Escalante A. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum 2001;44:2737–45.
Endothelial dysfunction and subclinical atherosclerosisas evidenced by the measurement of flow mediated (10) Bax L, Yu LM, Ikeda N, Tsuruta H, Moons KG. Development and validation of MIX: comprehensive free software for meta-analysis of causal research data. BMC Med Res Methodol 2006;6(6):50. (11) Tyrrel PN, Beyene J, Feldman BM, McCrindle BW, Silverman ED, Bradley JT. Rheumatic disease and carotid intima-media thickness: a systematic review and meta-analysis. Epud May 2010;30(5):1014–26. (12) Ciftci O, Yilmaz S, Topcu S, Cahskan M, Gullu H, Erdogan D, et al. Impaired coronary microvascular function and increased intima–media thickness in rheumatoid arthritis. Atherosclerosis 2008;198:332–7. (13) Van Sijl AM, Peters MJ, Knol DK, de Vet HC, Gonzalez-Gay MA, Smulders YM, et al. Carotid intima media thickness in rheumatoid arthritis as compared to control subjects: a metaanalysis. Semin Arthritis Rheum 2011 Apr;40(5):389–97. (14) Roman MJ, Moeller E, Davis A, Paget SA, Crow MK, Lockshin MD. Atherosclerosis in patients with rheumatoid arthritis. Ann Intern Med 2006;144(4):249–56. (15) Kumeda Y, Inaba M, Goto H, Nagata M, Henmi Y, Furumitsu Y. Increased thickness of the arterial intima-media detected by ultrasonography in patients with rheumatoid arthritis. Arthritis Rheum 2002;46(6):1489–97. (16) Mahajan V, Handa R, Kumar U, Sharma S, Gulati G, Pandey RM. Assessment of atherosclerosis by carotid intimomedial thickness in patientswith rheumatoid arthritis. J Assoc Physicians India 2008;56:587–90.
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(17) O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK. Cardiovascular health study collaborative research group. Carotid artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. N Engl J Med 1999;340(1):14–22. (18) Doornum SV, McColl G, Jenkins A, Green DJ, Wicks IP. Screening for atherosclerosis in patients with rheumatoid arthritis: comparison of two in vivo tests of vascular fubnction. Arthritis Rheum 2003;46:862–73. (19) Bacon PA, Stevens RJ, Carruthers DM, Young SP, Kitas GD. Acclerated atherogenesis in autoimmune rheumatic disease. Review 2002;1(6):338–47. (20) Juanatey CG, Llorca J, Martin J, Gonzalez-Gay MA. Carotid intima–media thickness predicts the development of cardiovascular events in patients with rheumatoid arthritis. Semin Arthritis Rheum 2009;38:366–71. (21) Schroeder S, Enderle MD, Baumbach A, Enseleit F, Chenevard R, Distlcr O, et al. Influence of vessel size, age and body mass index on the flow–mediated dilatation of the brachila artery. Int J Cardiol 2000;76:219–25. (22) Hurlimann D, Forster A, Noll G. Anti tumour necrosis factor– alpha treatment improves endothelial function in patients with rheumatoid arthritis. Circulation 2002;106:2184–7. (23) Quyyumi AA. Inflamed joints and stiff arteries: is rheumatoid arthritis a cardiovascular risk factor? Circulation 2006;114: 1137–9.
Egyptian Society of Radiology and Nuclear Medicine
The Egyptian Journal of Radiology and Nuclear Medicine www.elsevier.com/locate/ejrnm www.sciencedirect.com
ORIGINAL ARTICLE
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 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 2012 Available online 6 February 2013
KEYWORDS Rheumatoid arthritis; Endothelial dysfunction; Brachial artery flow mediated dilatation; Carotid intima media thickness
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 thickness 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 function assessment by means of FMD as a useful tool to predict the increased risk of cardiovascular
Abbreviations: RA, rheumatoid arthritis; CVD, cardiovascular disease; FMD, flow mediated dilatation; NO, nitric oxide; CIMT, carotid intima media thickness; ED, endothelial dysfunction. * Corresponding author. Address: Tanta University Hospital, Tanta, Gharbeya, Egypt. Tel.: +20 1068643995. E-mail addresses: [email protected] (N.M. AbdelMaboud), [email protected] (H.H. Elsaid). 1 Address: Tanta University Hospital, Tanta, Gharbeya, Egypt. Tel.: +20 1223658711. Peer review under responsibility of Egyptian Society of Radiology and Nuclear Medicine.
Production and hosting by Elsevier 0378-603X Ó 2013 Egyptian Society of Radiology and Nuclear Medicine. Production and hosting by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ejrnm.2012.12.009
238
N.M. AbdelMaboud, H.H. Elsaid disease in patients with rheumatoid arthritis. We suggest that the carotid artery US should be performed for all patients with rheumatoid arthritis to establish the risk of cardiovascular complication which requires more aggressive therapy. Ó 2013 Egyptian Society of Radiology and Nuclear Medicine. Production and hosting by Elsevier B.V. All rights reserved.
1. Introduction Rheumatoid arthritis (RA) is the most common systemic autoimmune disease. Patients with rheumatoid arthritis are at increased risk for cardiovascular diseases (CVD), one of the earliest manifestations of CVD is endothelial dysfunction(ED) (1). The endothelium is the innermost lining of the vasculature and is responsible for maintaining vascular homeostasis via the balanced production of a number of vasoactive factors such as nitric oxide (NO) which play an important role in vasodilatation and inhibiting the atherosclerotic process (2). Damage to the endothelium can reduce (NO) activity, causing endothelial dysfunction which is an early indicator of CVD (3). ED is an important sign of early atherosclerosis and can be assessed non invasively by the impairment of endothelial dependant flow 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 indicator of atherosclerosis and future CVD (5).
insufficiency or received drugs affecting the cardiovascular system. 20 healthy volunteers were recruited as control .Written consent was taken from all patients and the control group and 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 hyperextension of the neck .Both common carotid arteries were examined using a 7 MHz linear array transducer in a PHILIPS HD11 instrument. Carotid intima –media thickness and lumen diameter were measured from end diastolic M-mode images (minimum distension) of the wall of the distal common carotid artery in a location not containing plaque. The greater distance between lumen – intima and media-adventitia interface was measured. The mean value of the two sides was taken.
2. Patients and methods
2.3. Flow mediated vasodilatation of brachial artery
2.1. Patients and control
The procedure was performed on the same US machine and the same transducer as used in carotid US. The subject lies in a supine position; the right brachial artery was scanned in longitudinal section 2–15 cm. above the antecubital fossa with B-mode. The clearest picture of the artery at the center was obtained (the transducer was kept constant throughout the procedure by noting the relation of the artery with the adjacent anatomical landmarks).The luminal diameter of the artery was measured by calculating the distance between the proximal and distal intima. Ischemia was induced with a sphygmomanometer cuff placed around the forearm distal to the scanned region inflated to 200 mmHG for 4 min and then released. A second scan was taken at this stage and the luminal diameter was measured 60 s. after cuff deflation .The endothelium dependant function is defined by the formula: D2-D1/D1x100 the higher the numeric value of the study , the better the endothelial function. ED is considered when the FMD is <4.55
The subjects in the present study were 26 RA patients (23 females 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
Table 1 group.
The brachial artery diameter and FMD in the control
Number
D1 (mm)
D2 (mm)
FMD (%)
5 7 8
2.5 3 3.2
3 3.7 4
20 23.3 25
Fig. 1a
The basal diameter of the brachial artery in a normal subject = 3.2 mm.
Endothelial dysfunction and subclinical atherosclerosisas evidenced by the measurement of flow mediated
Fig. 1b
239
The post- occlusion diameter of brachial artery in the same person = 4 mm, FMD 25% denoting good endothelial function.
3. Results
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)
10 8 3 5
4.3 4.1 3 3
4.3 4.3 3.2 3.4
Fig. 2a
FMD (%) 0 4.8 6.6 96.6
This study included 26 patients of rheumatoid arthritis with an age 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 release of ischemia (D2) 3 mm, the FMD was 20%.D1was 3 mm in seven 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. 1a and b. Table 2 shows the characteristics of the rheumatoid arthritis group in which the diameter of the brachial artery before the induction of ischemia (D1) was 4.3 mm in 10 subjects, after the release of ischemia (D2) 4.3 mm, the FMD was 0% D1 was 4.1 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 was 6.6%. D1 was 3 in five subjects, D2 was 3.4 mm and the FMD was –96.6% Figs. 2a and b, 3a and b, 4a and b. So, the higher the numeric value of the FMD, the better the endothelial function. The CIMT in the control group was 0.44 mm in eight persons, 0.47 mm in nine persons, and 0.35 mm in three persons Fig. 1c Table 3. The CIMT in the rheumatoid arthritis patients was 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.
The basal diameter of the brachial artery in a patient with rheumatoid arthritis = 4.3 mm.
240
Fig. 2b
N.M. AbdelMaboud, H.H. Elsaid
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 cardiovascular mortality [6]. Almost half of all deaths in rheumatoid arthritis results from cardiovascular causes (7). Therefore, it may be suggested that the main cause of mortality and morbidity is ischemic heart disease in patients with RA (7). Discovery
Fig. 3a
of early interventions in RA disease that might influence atherosclerotic progression are essentials to determine approaches that could in turn reduce the subsequent risk of cardiovascular mortality (8,9). CIMT is a known strong predictor of cardiovascular events in the general population (10), and has been predominantly 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 results were the same as Gonzalez–Juanatey C et al. (12) in which the presence of subclinical atherosclerosis, manifested by increased value of CIMT is consistent with the high rate of silent ischemic heart diseases and sudden cardiac death observed in RA patients. Van Sijl AM et al (13) proved in their study that CIMT is frequently used to identify the population at elevated cardiovascular risk. (17) The results of our study implicate that the mean CIMT of the common carotid artery was significantly higher in RA patients than in healthy subjects. Van Sijl AM etal (13), found that the CIMT difference between RA patients and the control subject may be very small as inHiggins JP 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 ultrasound protocols for determining CIMT between all studies is an important observation but also complicates the interpretation of the individual study results. Still, they think that the differences in ultrasound protocols or in other methodological aspects are unlikely to have caused a systematic bias toward under - or overestimation of CIMT difference between RA patients and control. So, US scanning of CIMT has been shown to be an accurate method for estimating cardiovascular risk
The basal diameter of brachial artery in a patient with rheumatoid arthritis = 4.1 mm.
Endothelial dysfunction and subclinical atherosclerosisas evidenced by the measurement of flow mediated
Fig. 3b
241
The post- occlusion diameter of brachial artery in the same person = 4.3 mm, FMD 4.8% denoting poor endothelial function.
Fig. 3c The carotid intima media thickness in the same person 0.64 mm.
(17). RA appears to be associated with accelerated atherosclerosis, the mechanisms involved are not clear, but may include endothelial 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
in the atheromatous lesion, so its evaluation is a promising tool for the estimation of coronary affection. Castro PT et al. (19) study mentioned that FMD allows an adequate evaluation of endothelial behavior and reflects the coronary endothelial function and behavior inspite of that the ideal method for diagnosing endothelial dysfunction has not been established yet. Our study coincides with those of Schroeder S et al. (20) in which the age of the patient does not affect the endothelial function evaluation with FMD. We have found no significant difference in the different age groups of patients and the control group regarding the FMD .Like the present study, other studies like Hurlimann D et al. (21) have found a significant endothelial dysfunction in patients with autoimmune disease like RA by means of FMD .The presence of systemic inflammation predisposes to atherosclerosis, affecting the endothelial function and decreasing the production of nitric oxide by the endothelium, this decrease in the nitric oxide production leads to a smaller arterial dilatation upon induced ischemia. Quyyumi AA (22) affirms that systemic inflammation markers like FMD, CIMT and pulse wave analysis arise as a method for evaluating the atherosclerosis risk .He recommends the inclusion of these methods in randomized study for screening and diagnosis of cardiovascular risk. Considering that a high level of systemic inflammation affects the endothelial function, inflammation markers like FMD may provide a better evaluation for the cardiovascular risk in patients with RA (23). In our study, we demonstrate that the FMD and
The basal diameter of brachial artery in a patient with rheumatoid arthritis = 3 mm.
242
Fig. 4b
N.M. AbdelMaboud, H.H. Elsaid
The post-occlusion diameter of brachial artery in the same person = 3.2 mm, FMD 6.6% denoting poor endothelial function.
5. Conclusion The results from the present study support the use of carotid US and endothelial function assessment by means of FMD as a useful tool to predict the increased risk of cardiovasculr disease in patient with rheumatoid arthritis. We suggest that the carotid artery US should be performed for all patients with rheumatoid arthritis to establish the risk of cardiovascular complication which requires more aggressive therapy. References
Fig. 4c The carotid intima media thickness in the same person 0.50 mm.
Table 3
CIMT in the control group.
Number
CIMT (mm)
8 9 3
0.44 0.47 0.35
Table 4
CIMT in the rheumatoid arthritis patients.
Number
CIMT (mm)
10 9 7
0.50 0.54 0.56
CIMT are promising methods for the evaluation of RA and are very helpful for the prevention of vascular risk.
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