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ORIGINAL ARTICLE
Year : 2018  |  Volume : 31  |  Issue : 3  |  Page : 800-804

Intima media thickness measurement as a marker of subclinical atherosclerosis in systemic lupus erythematosus patients


1 Department of Physical Medicine, Rheumatology and Rehabilitation, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Cardiology, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission08-Apr-2017
Date of Acceptance18-Jun-2017
Date of Web Publication31-Dec-2018

Correspondence Address:
Dalia A Nofal
Department of Physical Medicine, Rheumatology and Rehabilitation, Faculty of Medicine, Menoufia University, Shebin Elkom
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_262_17

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  Abstract 


Objective
The aim of this study was to evaluate subclinical atherosclerosis in patients with systemic lupus erythematosus (SLE) and its relationship to disease activity and damage indices.
Background
Increased morbidity and mortality in patients with SLE is mostly due to cardiovascular events. Assessment of the intima media thickness (IMT) using B-mode ultrasonography at the carotid artery level is a noninvasive measure to assess subclinical atherosclerosis.
Patients and methods
The study included 60 patients with SLE (female:male 57:3) in addition to 20 healthy volunteers (female:male 16:4) as a control group. These patients were diagnosed with SLE according to the modified American College of Rheumatology criteria for classification of SLE. IMT was measured using B-mode ultrasound on both sides. The results were correlated with lipid profile, anticardiolipin antibodies, and lupus anticoagulant complement components. Clinical disease activity and damage were evaluated using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics (SLICC) indices.
Results
There was a highly significant difference between patients and controls regarding IMT; it was higher in patients (0.84) than in controls (0.61) and P value less than 0.001. There was a positive correlation between age, duration, erythrocyte sedimentation rate, low-density lipoprotein, cholesterol, SLEDAI and SLICC score, and IMT, and a negative correlation between complement 4 (C4) and IMT.
Conclusion
Subclinical atherosclerosis is frequent in patients with SLE. The occurrence of premature atherosclerosis increases with increased disease activity and damage index.

Keywords: intima media thickness, subclinical atherosclerosis, systemic lupus


How to cite this article:
Soliman SG, Labeeb AA, Soltan GM, Nofal DA. Intima media thickness measurement as a marker of subclinical atherosclerosis in systemic lupus erythematosus patients. Menoufia Med J 2018;31:800-4

How to cite this URL:
Soliman SG, Labeeb AA, Soltan GM, Nofal DA. Intima media thickness measurement as a marker of subclinical atherosclerosis in systemic lupus erythematosus patients. Menoufia Med J [serial online] 2018 [cited 2019 Jun 19];31:800-4. Available from: http://www.mmj.eg.net/text.asp?2018/31/3/800/248735




  Introduction Top


Subclinical atherosclerosis has occurred with many rheumatic diseases such as rheumatoid arthritis[1], osteoarthritis[2], Behcet's disease[3], and systemic sclerosis[4].

Patients with systemic lupus erythematosus (SLE) have an increased risk for the occurrence of atherosclerotic cardiovascular disease (CVD) compared with age-matched controls of up to 50 folds[5].

Chronic inflammation and immune dysregulation in SLE contribute to the accelerated vascular disease seen in these patients[6]. This may be the cause of an increased risk for accelerated atherosclerosis in patients with lupus with higher disease activity[7].

Many studies have shown that hypertension, diabetes mellitus, obesity, hyperlipidemia, smoking, and a sedentary lifestyle play a role in accelerated atherosclerosis[8]. The diagnosis of SLE is a strong risk factor for CVD, even after controlling for traditional risk factors[9].

IMT is a sensitive marker for early stages of atherosclerosis and is considered to be a marker of generalized atherosclerosis. B-mode ultrasound examination of the carotid artery is a successful tool for detecting this early atherosclerosis[10].

The aim of this study was to evaluate subclinical atherosclerosis in patients with SLE and its relationship to disease activity and damage indices.


  Patients and Method Top


A total of 60 patients diagnosed with SLE and 20 age-matched and sex-matched controls were included in this study. They were randomly recruited from the Internal Medicine, Physical Medicine, Rheumatology, and Rehabilitation Clinic, Menoufia University Hospitals, during the years 2015–2016. The study included both sexes. In all, 57 (95%) patients were females and three (5%) were males. Their age ranged from 20 to 45 years. Their disease duration ranged from 1 to 15 years.

The selection of patients was based on the modified American College of Rheumatology (ACR) criteria for classification of SLE[11].

Informed written consent was obtained from every patient before his or her enrollment in the trial.

Randomization was performed as listed by the randomization technique in Microsoft Excel Program (Microsoft for Windows, USA).

Exclusion criteria include pregnant patients, patients suffering from diabetes, hypertension, metabolic syndrome, obese patients having BMI greater than 30, smokers, patients having any other autoimmune disease, patients with history of any CVD, and patients with a history of atherosclerosis before SLE onset.

Inclusion criteria include patients were diagnosed as having SLE according to the modified ACR criteria for classification of SLE[11] with disease duration of at least 6 months. All patients are under medical treatment for SLE.

All patients were subjected to the following.

Demographic data recording (age and sex), history taking, and clinical examination (general examination[12] and local examination of joints[13]).

Laboratory investigations: complete blood count, erythrocyte sedimentation rate, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, serum urea and creatinine, urine analysis, antinuclear antibodies, antidouble stranded DNA, complement 3 (C3), C4, total lipid profile, C-reactive protein titer, 24 h proteinuria, anticardiolipin antibody, lupus anticoagulant, and creatinine clearance.

Carotid ultrasonography to assess IMT: patients and controls were scanned using Philips HDI 5000 (Midland, ON, Canada) device with 7.5–12 MHs probe; the intima media thickness (IMT) measurements on each side were taken at the following points: common carotid artery (10 mm before the bulb), bulb (5–10 mm cranially to the start of the bulb), and internal carotid artery (10 mm after flow divider). For each patient the highest IMT among the six segments studied were recorded.

Assessment of disease activity using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)[14].

Assessment of disease damage using the Systemic Lupus International Collaborating Clinics (SLICC) score[15].

Statistical analysis

Data were collected and entered into the computer using statistical package for the social sciences (SPSS) program for statistical analysis (version 20; SPSS Inc., Chicago, Illinois, USA).

  1. Descriptive statistics: quantitative data were presented in the form of mean, SD, range, and qualitative data were presented in the form of numbers and percentages
  2. Analytical statistics: used to find out the possible association between studied factors and the targeted disease. The used tests of significance included the following:


    1. χ2 was used to study association between two qualitative variables
    2. Fisher's exact test: for 2 × 2 tables when expected cell count of more than 25% of cases were less than 5
    3. Student's t-test: is a test of significance used for comparison between two groups having quantitative variables
    4. Kruskal–Wallis test (nonparametric test): is a test of significance used for comparison between three or more groups not normally distributed having quantitative variables
    5. Pearson's correlation (r): is a test used to measure the association between two quantitative variables.


    P value of greater than 0.05 nonsignificant; P value of less than 0.05 significant; P value of less than 0.001 was considered statistically highly significant.


      Results Top


    This study included 60 patients, 57/60 (95%) female and 3/60 (5%) male. The mean age was 31.8 ± 8.79 years, ranging from 20 to 45 years.

    In this study there was no significant difference between patients and controls regarding age and sex [Table 1].
    Table 1: Demographic data of studied groups

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    Regarding ultrasound findings 60% of patients had negative ultrasound findings and 40% of patients had positive ultrasound findings [Table 2].
    Table 2: Ultrasound findings among patients group (n=60)

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    There was a highly significant difference between patients and controls regarding IMT; it was higher in patients (0.84) than in controls (0.61) and P value less than 0.001 [Table 3].
    Table 3: Intima media thickness among studied groups

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    There was a positive correlation between age, duration, ESR, low-density lipoprotein, cholesterol, SLEDAI and SLICC score, and IMT. There was also a negative correlation between C4 and IMT [Table 4].
    Table 4: Correlation between intima media thickness and clinical and laboratory data in the patient group

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    There was a highly significant difference between patients with normal IMT, those with increased IMT, and those with increased IMT with plaque formation as per their SLICC score; it was higher in patients with plaque than in those with increased IMT only and than in those with normal IMT [Table 5].
    Table 5: Relation between systemic lupus international collaborating clinics (Systemic Lupus International Collaborating Clinics score) and ultrasound findings in the patient group

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    There was a highly significant difference between patients with normal IMT, those with increased IMT, and those with increased IMT with plaque formation as per their disease activity (SLEDAI). It is also shown that 50% of patients with normal IMT have moderate disease activity, 50% of patients with increased IMT have high disease activity, and 50% of patients with increased IMT with plaque formation have very high activity [Table 6].
    Table 6: Relation between Systemic Lupus Erythematosus Disease Activity Index and ultrasound findings in the patient group (n=60)

    Click here to view



      Discussion Top


    The aim of our study was to assess the carotid artery IMT as an index of subclinical carotid atherosclerosis in patients with SLE and its correlation with disease activity and severity.

    Our study included 60 SLE patients with a mean age of 31.8 ± 8.79 and with a mean disease duration of 4.95 ± 3.61 years in addition to 20 age-matched and sex-matched controls. The selection of patients was based on the modified ACR criteria for classification of SLE[11].

    The results of our study showed that 24 (40%) of our patients showed positive sonographic findings (significant increase in IMT thickness, i.e., IMT >0.9 mm or presence of plaque), 12 (20%) of them showed an increase in IMT only, and 12 (20%) of them showed increased IMT with plaque formation.

    In agreement with our findings, a significant increase in IMT has been reported in other studies; 28% of patients with positive ultrasound findings[16] and 37% of patients with positive ultrasound findings[17]. Another study reported an incidence of 23.33% and also found atherosclerotic plaques in 5% of their patients[18]. The results of another author showed that patients with SLE who were less than 55 years old had more plaques than did controls of the same age (21 vs. 3% in controls; P < 0.01)[19]. This is also similar to what has been reported by many other authors[20].

    In our study the IMT in patients was at a mean of 0.84 ± 0.24 whereas IMT in controls was at a mean of 0.61 ± 0.14 (highly significant difference between patients and controls regarding IMT).

    In agreement with our results, a very highly significant statistical difference in IMT between patients and controls was reported[21].

    In our study 50% of patients with normal IMT have moderate disease activity, 50% of patients with increased IMT have high disease activity, and 50% of patients with increased IMT with plaque formation have very high activity.

    An important nontraditional risk factor for atherosclerosis is disease activity in systemic lupus[22], whereas systemic lupus disease activity is a modifiable risk factor for coronary artery calcifications in SLE[23].

    Our study shows a highly significant difference between patients with negative ultrasound findings and those with positive ultrasound findings (increased IMT only or increased with plaque) regarding their SLICC score; it was higher in patients with positive ultrasound findings with plaque formation than in patients with negative ultrasound findings.

    In agreement with our findings, studies have found plaque formations in systemic lupus is related to many factors such as SLIC damage index[24]. Also patients with SLE with coronary heart disease have damage on the SLIC damage index[25].

    Upon analyzing the correlation of clinical, laboratory, and disease activity data in patients with positive sonographic findings, the only correlation significant was with 24 h urinary proteins. This result was different from our study results that show a positive correlation between age, duration, ESR, low-density lipoprotein, cholesterol, SLEDAI and SLICC score, and IMT, and also show a negative correlation between C4 and IMT[21].

    In agreement with our findings, a significant correlation between IMT and disease duration and age was reported[26].

    No significant correlation to classical parameters of SLE activity such as levels of C3, C4 components of complement, parameters of lipid metabolism, or to SLEDAI index have been reported, which is in contrast to our result. The differences could be explained by the heterogeneity of the lupus patients and the influence of treatment[26].

    Finally, we can say that SLE is considered as a risk factor for accelerated atherosclerosis and this is increased by multiple factors as active disease, damage index, age of patients, duration of disease, etc. The higher the number of risk factors, the higher the incidence of premature atherosclerosis. The differences between different studies in detection of risk factors that leads to premature atherosclerosis may be attributed to many factors, e.g. difference in methodology for assessment of atherosclerosis, difference in selection of cases, difference in the cutoff point between normal and high IMT, which is different in other studies. IMT less than or equal to 0.7 mm is normal in one study[27], whereas in another study, normal IMT is considered less than or equal to 0.9 mm[16].


      Conclusion Top


    SLE is associated with increased risk of accelerated atherosclerosis. Noninvasive technique like B-mode ultrasound scanning to detect carotid IMT and carotid plaques can be used to identify patients with SLE with cardiovascular risk.

    Risk for premature atherosclerosis increased with an increase in disease activity and damage score.

    Control of disease activity and prevention of organ damage can help to reduce incidence of atherosclerosis in SLE patients.

    Financial support and sponsorship

    Nil.

    Conflicts of interest

    There are no conflicts of interest.



     
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        Tables

      [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



     

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