Originalien Z Rheumatol 2014 DOI 10.1007/s00393-014-1473-1 © Springer-Verlag Berlin Heidelberg 2014
S. Fadda1 · H. Nassar1 · S.M. Gamal1 · H. Al-azizi2 1 Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University, Cairo 2 Radiology department, Faculty of Medicine, Cairo University, Cairo
Subclinical atherosclerosis in systemic lupus erythematosus patients and its relationship to disease activity and damage indices Systemic lupus erythematosus (SLE) is an autoimmune disease [1] that occurs predominantly in women [2] and affects many organ systems. Even though the etiology is still unknown, a distinct association is found with several immune response genes [3]. Subclinical atherosclerosis has been reported in many rheumatic diseases— such as rheumatoid arthritis [4, 5], osteoarthritis [6], Behcets disease [7] and systemic sclerosis [8]. Patients with SLE have an up to a 50fold increased risk of developing atherosclerotic cardiovascular disease compared to age-matched controls [9]. Recent advances in the etiology of vascular damage in this disease have stressed the relevance of the interplay between lupus-specific inflammatory factors and traditional cardiac risk factors in causing increased endothelial damage [10]. The chronic inflammation and immune dysregulation characteristics of SLE undoubtedly contribute to the accelerated vascular disease seen in these patients [11]. This may serve as an explanation for the increased risk of premature atherosclerosis in lupus patients with higher disease activity [12, 13]. The survival of SLE patients has improved during the past three decades; however, they still die at a rate that is three-times higher than that of the general population [14]. It is now clear that premature atherosclerotic cardiovascular disease is one of the major causes of increased morbidity and mortality in these patients [15]. Noninvasive measures to assess subclinical atherosclerosis are based on the assessment of the intima–media thickness
(IMT) and detection of plaque formation using B mode ultrasonography at the carotid artery level [16]. The IMT may be the most sensitive marker for the earliest stages of atherosclerosis and is considered to be a marker of generalized atherosclerosis. B mode ultrasound examination of the carotid artery has been successful in detecting this early atherosclerosis [17]. This study aimed to detect the incidence of premature atherosclerosis in SLE patients and to study its association with disease activity and damage indices.
Patients and methods This study included 50 female SLE patients who satisfied at least four of the modified American College of Rheumatology (ACR) criteria for classification of SLE [18]. Patients were recruited from the Rheumatology and Rehabilitation Department, Cairo University hospital. Patients were taken consecutively. The control group comprised 25 age- and gendermatched controls. Full case history was taken from all patients, and all were subjected to detailed clinical examination and routine laboratory investigations. Assessment of disease activity was performed using the Systemic Lupus Erythematosus Disease Actively Index (SLEDAI) [19] and disease damage was assessed using the Systemic Lupus International Collaborating Clinics (SLICC) score [20]. Furthermore, carotid ultrasonography was performed for patients and controls to assess IMT.
Sonographic evaluation of intima–media thickness Patients were scanned using a Philips HDI 5000 (Philips Healthcare, Andover, MA, USA) using a 7.5–12-MHz probe. IMT measurements were taken on each side at the common carotid artery (10 mm before the bulb), the bulb (5–10 mm cranial to its start) and internal carotid artery (10 mm after flow divider). For each patient, the highest IMT among the six segments studied was recorded. According to current sonographic criteria, a normal IMT was referred to when this was 0.9 mm) was considered indicative of thickened intima and IMT >1.3 mm was indicative of an atherosclerotic plaque [21]. The study was approved by the local ethics committee and conforms to the standards currently applied in Cairo University Teaching Hospitals. The included patients all gave their consent to be enrolled in the study.
Statistical analysis The clinical, laboratory and radiological data were recorded on an investigative report form. These data were transferred to IBM card using IBM PC with the SPSS for windows version 6.21 statistical program (SPSS Inc., Chicago, IL, USA) in order to obtain the means, standard deviations and ranges (minimum–maximum). Comparisons were performed using the student’s All authors approved the entirety of the submitted material and contributed actively to the study. Zeitschrift für Rheumatologie 2014
| 1
Originalien Tab. 1 Comparison between patients with significant and nonsignificant sonographic find-
ings Mean ± SD Age (years) Duration (years) Max. steroid (mg/d) Current steroid dose (mg/d) Systolic BP (mmHg) Diastolic BP (mmHg) ESR (mm/h) Urinary protein (g/24 h) TG (mg/dl) Cholesterol (mg/dl) LDL (mg/dl) HDL (mg/dl) C3 (mg/dl) SLEDAI SLICC IMT
Positive ultrasound (thickened intima) 29.9±8.09 4.15±4.46 47.66±12.56 23.66±10.56 146.3±20.78 95.46±21.45 65.82±25.87 1.43±1.89 235.23±79.8 257.37±57.21 150.29±34.94 31.39±11.42 71.38±23.12 21.44±3.31 1.78±1.21 1.08±0.14
Negative ultrasound (normal intima) 26.24±8.54 3.18±3.85 32.18±3.5 18.8±11.84 131.54±17.04 87.03±11.14 39.52±23.56 0.53±0.71 145.32±76.2 205.81±61 134.91±50.23 43.2±9.27 75.94±26.78 8.93±4.73 1.3±0.60 0.76±0.09
P-value 0.03* 0.28 0.0009** 0.12 0.01* 0.059 0.0027** 0.01* 0.0007** 0.0045** 0.14 0.002** 0.26
S. Fadda1 · H. Nassar1 · S.M. Gamal1 · H. Al-azizi2 1 Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University, Cairo 2 Radiology department, Faculty of Medicine, Cairo University, Cairo
Subclinical atherosclerosis in systemic lupus erythematosus patients and its relationship to disease activity and damage indices Systemic lupus erythematosus (SLE) is an autoimmune disease [1] that occurs predominantly in women [2] and affects many organ systems. Even though the etiology is still unknown, a distinct association is found with several immune response genes [3]. Subclinical atherosclerosis has been reported in many rheumatic diseases— such as rheumatoid arthritis [4, 5], osteoarthritis [6], Behcets disease [7] and systemic sclerosis [8]. Patients with SLE have an up to a 50fold increased risk of developing atherosclerotic cardiovascular disease compared to age-matched controls [9]. Recent advances in the etiology of vascular damage in this disease have stressed the relevance of the interplay between lupus-specific inflammatory factors and traditional cardiac risk factors in causing increased endothelial damage [10]. The chronic inflammation and immune dysregulation characteristics of SLE undoubtedly contribute to the accelerated vascular disease seen in these patients [11]. This may serve as an explanation for the increased risk of premature atherosclerosis in lupus patients with higher disease activity [12, 13]. The survival of SLE patients has improved during the past three decades; however, they still die at a rate that is three-times higher than that of the general population [14]. It is now clear that premature atherosclerotic cardiovascular disease is one of the major causes of increased morbidity and mortality in these patients [15]. Noninvasive measures to assess subclinical atherosclerosis are based on the assessment of the intima–media thickness
(IMT) and detection of plaque formation using B mode ultrasonography at the carotid artery level [16]. The IMT may be the most sensitive marker for the earliest stages of atherosclerosis and is considered to be a marker of generalized atherosclerosis. B mode ultrasound examination of the carotid artery has been successful in detecting this early atherosclerosis [17]. This study aimed to detect the incidence of premature atherosclerosis in SLE patients and to study its association with disease activity and damage indices.
Patients and methods This study included 50 female SLE patients who satisfied at least four of the modified American College of Rheumatology (ACR) criteria for classification of SLE [18]. Patients were recruited from the Rheumatology and Rehabilitation Department, Cairo University hospital. Patients were taken consecutively. The control group comprised 25 age- and gendermatched controls. Full case history was taken from all patients, and all were subjected to detailed clinical examination and routine laboratory investigations. Assessment of disease activity was performed using the Systemic Lupus Erythematosus Disease Actively Index (SLEDAI) [19] and disease damage was assessed using the Systemic Lupus International Collaborating Clinics (SLICC) score [20]. Furthermore, carotid ultrasonography was performed for patients and controls to assess IMT.
Sonographic evaluation of intima–media thickness Patients were scanned using a Philips HDI 5000 (Philips Healthcare, Andover, MA, USA) using a 7.5–12-MHz probe. IMT measurements were taken on each side at the common carotid artery (10 mm before the bulb), the bulb (5–10 mm cranial to its start) and internal carotid artery (10 mm after flow divider). For each patient, the highest IMT among the six segments studied was recorded. According to current sonographic criteria, a normal IMT was referred to when this was 0.9 mm) was considered indicative of thickened intima and IMT >1.3 mm was indicative of an atherosclerotic plaque [21]. The study was approved by the local ethics committee and conforms to the standards currently applied in Cairo University Teaching Hospitals. The included patients all gave their consent to be enrolled in the study.
Statistical analysis The clinical, laboratory and radiological data were recorded on an investigative report form. These data were transferred to IBM card using IBM PC with the SPSS for windows version 6.21 statistical program (SPSS Inc., Chicago, IL, USA) in order to obtain the means, standard deviations and ranges (minimum–maximum). Comparisons were performed using the student’s All authors approved the entirety of the submitted material and contributed actively to the study. Zeitschrift für Rheumatologie 2014
| 1
Originalien Tab. 1 Comparison between patients with significant and nonsignificant sonographic find-
ings Mean ± SD Age (years) Duration (years) Max. steroid (mg/d) Current steroid dose (mg/d) Systolic BP (mmHg) Diastolic BP (mmHg) ESR (mm/h) Urinary protein (g/24 h) TG (mg/dl) Cholesterol (mg/dl) LDL (mg/dl) HDL (mg/dl) C3 (mg/dl) SLEDAI SLICC IMT
Positive ultrasound (thickened intima) 29.9±8.09 4.15±4.46 47.66±12.56 23.66±10.56 146.3±20.78 95.46±21.45 65.82±25.87 1.43±1.89 235.23±79.8 257.37±57.21 150.29±34.94 31.39±11.42 71.38±23.12 21.44±3.31 1.78±1.21 1.08±0.14
Negative ultrasound (normal intima) 26.24±8.54 3.18±3.85 32.18±3.5 18.8±11.84 131.54±17.04 87.03±11.14 39.52±23.56 0.53±0.71 145.32±76.2 205.81±61 134.91±50.23 43.2±9.27 75.94±26.78 8.93±4.73 1.3±0.60 0.76±0.09
P-value 0.03* 0.28 0.0009** 0.12 0.01* 0.059 0.0027** 0.01* 0.0007** 0.0045** 0.14 0.002** 0.26
