Lupus (2014) 23, 1517–1522 http://lup.sagepub.com
CONCISE REPORT
Carotid subclinical atherosclerosis is associated with disease activity but not vitamin D in Korean systemic lupus erythematosus J-Y Jung, B-R Koh, C-B Bae, H-A Kim and C-H Suh Department of Rheumatology and BK21 Division of Cell Transformation and Restoration, Ajou University School of Medicine, Suwon, Korea
Atherosclerosis develops early in systemic lupus erythematosus (SLE) patients and is an important cause of mortality. Vitamin D deficiency is found to be associated with cardiovascular disease and autoimmunity. We evaluated the extent of carotid subclinical atherosclerosis and analyzed its correlation with vitamin D in SLE. One hundred and two female patients with SLE and 52 normal controls (NCs) were recruited. The mean carotid intima-media thickness (IMT) of SLE patients was 0.41 0.08 mm, which was higher than that of NCs (0.32 0.08 mm, p ¼ 0.012). In addition, carotid plaques were more frequent and the plaque index was higher in SLE patients than in NCs (0.68 1.39 vs. 0.26 0.87, p ¼ 0.026). Carotid IMT was correlated with age, body mass index, SLE disease activity index, and aspirin use in SLE patients. The plaque index was correlated with renal involvement. Vitamin 25(OH)D3 level was not correlated with carotid IMT, plaque index or disease activity markers. In SLE, the risk of cardiovascular disease is higher than that in NCs, which may be derived from systemic inflammation. It may be not suitable to assess vitamin D as a marker of disease activity or subclinical atherosclerosis in SLE patients. Lupus (2014) 23, 1517–1522. Key words: Systemic lupus erythematosus; atherosclerosis; carotid artery; disease activity; vitamin D
Introduction Systemic lupus erythematosus (SLE) is a chronic disease arising from autoimmune dysregulation with diverse manifestations. It is well known that patients with SLE develop cardiovascular disease (CVD) frequently and early, which is a common cause of death.1 This phenomenon might be related to chronic inflammation, existence of autoantibodies, pathologic endothelial activation and prolonged immunosuppressive therapy, as it is not explained by traditional risk factors alone. Measurements of carotid artery intima-media thickness (IMT) and carotid artery plaque by Doppler ultrasound are useful and reliable for predicting CVD risk, and are also used as atherosclerosis prescreening tools.2
Correspondence to: Chang-Hee Suh, Department of Rheumatology and BK21 Division of Cell Transformation and Restoration Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu Suwon, Korea 443-380. Email: [email protected] Received 28 September 2013; accepted 30 June 2014
Vitamin D is synthesized in the skin following ultraviolet B exposure, with approximately 20% of the required vitamin D exogenously acquired from foods or supplements. Although 1,25(OH)2D3 is the main effector molecule, it is useful to check 25(OH)D3, which has a long halflife, to assess the vitamin D status. Currently, immunoradiometric assay is commonly used in estimating level of 25(OH)D3. Vitamin D affects malignancies, autoimmune diseases, infections and CVD.3 In the cardiovascular system, vitamin D deficiency causes endothelial dysfunction resulting in decreased vasodilation, a proinflammatory and prothrombotic state, and increased arterial stiffness.4 In the immune system, 1,25(OH)2D3 interacts and activates immune cells to release cytokines and transfers specific signals as an immune modulator. As vitamin D deficiency is common in SLE patients, vitamin D supplementation is expected to improve immune dysregulation.5 In this study, carotid IMT and carotid plaques were measured in patients with SLE and these factors were assessed in association with traditional risk factors for CVD and disease-related risk factors of SLE. The level of 25(OH)D3 was also
! The Author(s), 2014. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav
Downloaded from lup.sagepub.com at UCSF LIBRARY & CKM on May 13, 2015
10.1177/0961203314544185
Carotid subclinical atherosclerosis and vitamin D in SLE J-Y Jung et al.
1518
checked and evaluated as a marker of disease activity or CVD.
Methods Subject recruitment A total of 102 female SLE patients who visited the rheumatology outpatient clinic of Ajou University Hospital, and 52 age-matched healthy female normal controls (NCs), aged above 18 years, were recruited. All SLE patients met the diagnostic criteria of the American College of Rheumatology (ACR)6 and the patients were excluded if they had CVD, malignancy, chronic renal failure, or were pregnant. The traditional risk factors for CVD, which had been established to be able to predict further cardiovascular events, were assessed by chart review or participant interviews. None of the NC subjects had clinical evidence of myocardial infarction or cerebrovascular disease. Family history was defined as premature CVD before 55 years of age among first-degree male relatives or before 65 years of age among female relatives. Smoking status was defined as present if the subject smoked for more than 20 years despite cessation at the time of recruitment. The body mass index (BMI), calculated by height and weight, and the waist-hip ratio (WHR) of all participants were measured. Comprehensive medication histories, including corticosteroids, immunosuppressants, and anticoagulants, were obtained through patient interviews and chart reviews. All participants provided written informed consent. The study protocol was approved by the institutional review board of our hospital. Laboratory testing and disease activity assessment Laboratory testing included routine chemical analyses, complete blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), lipoprotein (Lp), and complement (C3 and C4). Additionally, autoantibody results were recorded, including those for antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA) antibody, anticardiolipin antibody (aCL) and lupus anticoagulant (LA). Vitamin D (25(OH)D3) levels were detected by immunoradiometric assay using the Bio-Line 25(OH)D3-Ria CT kit (Bio-Line S.A., Brussels, Belgium), according to the manufacturer’s instructions. The levels of 25(OH)D3 were detected around the same time during winter, from December to February. The season of detecting
must be the same because vitamin D synthesized in the skin changes seasonally because of different ultraviolet B (UVB) exposure. Clinical manifestations including arthritis, rash and renal involvement and the drug records of the patients were collected at the time carotid IMT and plaque were measured. Disease activity and disease-related damage were assessed at the time of enrollment using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)6 and Systemic Lupus International Collaborating Clinics/ACR Damage Index (SLICC/ACR DI), respectively. Measurement of carotid IMT and carotid plaque As biomarkers of subclinical atherosclerosis, carotid IMT and carotid plaques were measured using the 11 MHz linear transducer of Logiq P6 Pro (GE, Fairfield, CT, USA). Using B mode scanning the right and left common carotid arteries were scanned longitudinally and the bifurcation of the carotid artery was checked, then the calculated means of three portions were measured at 10 mm intervals from 10 mm upwards. Values from each side were then averaged to produce an overall measurement of the carotid IMT.6 Abnormal IMT was defined as the mean plus two standard deviations of the NC value. Carotid artery plaques were measured and the plaque index (PI) was calculated as previously described.7 The degree of plaque was graded 0 as no observed plaque; 1 as one small plaque (50%) or multiple plaques with medium plaque. The degrees measured at seven divided segments were summed. To minimize inter-observer-related bias, each test was performed by one investigator who was blinded to the clinical data. The intra-observer variability was 2.8%. Statistical analysis Demographic features, carotid IMT, carotid PI and 25(OH)D3 levels in the SLE and the NCs were compared using the Mann-Whitney U-test (non-parametric test). Also, carotid IMT, carotid PI and SLE-related markers between groups that were divided by 25(OH)D3 were compared using the Mann-Whitney U-test. The correlation carotid IMT with cardiovascular risk factors and SLE-related markers were determined using Spearman’s correlation coefficient. Two-sided p values of less than 0.05 were considered statistically significant. Statistical analysis was performed using version 12.0.1 of the Statistical Package for
Lupus Downloaded from lup.sagepub.com at UCSF LIBRARY & CKM on May 13, 2015
Carotid subclinical atherosclerosis and vitamin D in SLE J-Y Jung et al.
1519
the Social Sciences (SPSS; SPSS Inc, Chicago, IL, USA).
Results Characteristics of SLE patients and controls The characteristics and cardiovascular risk factors of the SLE patients and NCs are shown in Tables 1 and 2. In patients with SLE, 44 patients (43.1%) had arthritis, 17 patients (16.7%) had oral ulcers, and 14 patients (13.7 %) had lupus nephritis Table 1 Clinical characteristics and biochemical assessments of patients with SLE (n ¼ 102) Mean SD or n (%) Oral ulcer Malar rash Alopecia Arthritis Photosensitivity Renal disease Hemoglobin, g/dl Leukocyte, /ml Lymphocyte, /ml Platelet, 103/ ml ESR, mm/hour CRP, mg/dl Complement 3, mg/dl Complement 4, mg/dl Vitamin D (25(OH)D3), ng/ml Total cholesterol, mg/dl Triglyceride, mg/dl HDL, mg/dl LDL, mg/dl Dyslipidemia Anti-dsDNA antibody Anticardiolipin antibody Lupus anticoagulant Disease duration, months SLEDAI score Hydroxychloroquine use NSAID use Azathioprine use Cyclophosphamide use Mycophenolate mofetil use Aspirin use Statin use ACEI or ARB use Steroid use Steroid current dose, g Steroid cumulative dose, g
16 (15.7) 15 (14.7) 17 (16.7) 44 (43.1) 6 (5.9) 14 (13.7) 12.4 1.4 5,546 2,037 1,615 788 217 67.4 21.6 18.4 0.14 0.27 99.5 27.3 20.03 8.02 12.7 8.6 157.5 31.5 99.4 65.6 53.7 14.1 83.9 25.3 11 (10.7) 37 (36.3) 24 (23.5) 9 (8.8) 78.0 52.9 4.4 3.0 97 (95.1) 31 (30.4) 10 (9.8) 6 (5.8) 8 (7.8) 16 (15.7) 4 (3.7) 17 (16.7) 75 (73.5) 2.6 3.1 11.3 19
SLE: systemic lupus erythematosus; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; HDL: high-density lipoprotein; LDL: low-density lipoprotein; dsDNA: doublestranded deoxyribonucleic acid; SLEDAI: systemic lupus erythematosus disease activity index; NSAID: non-steroidal anti-inflammatory drugs; ACEI: angiotensin-converting enzyme inhibitor; ARB: angiotensin receptor blocker.
(Table 1). All patients had ANA, 37 patients (36.3%) had anti-dsDNA antibodies, 24 patients (23.5%) had aCL, and nine patients (8.8 %) had LA. The disease duration was 78.0 52.9 months, the SLEDAI value was 4.4 3.0, and only three patients had SLICC/ACR DI score 1. Ninetyseven patients (95.1%) took hydroxychloroquine, 15 patients (14.7%) took aspirin, and 75 patients (73.5%) took corticosteroids. The current corticosteroid dose was 2.6 3.1 mg, and the accumulated corticosteroids dose was 11.3 19.0 g of a prednisone equivalent. The BMI of patients with SLE was 21.1 2.8 (kg/m2) and the WHR was 0.81 0.06, which did not differ from those of NCs (21.8 2.5 kg/m2 and 0.8 0.07, respectively) (Table 2). Correlations between carotid IMT, carotid plaque, cardiovascular risk factors and clinical features The mean carotid IMT of SLE patients was 0.41 0.08 mm, which was higher than that of NCs (0.32 0.08 mm, p ¼ 0.012) (Table 2). And 23 patients (22.5%) showed significantly abnormal carotid IMT, which was more than 0.59 mm. Carotid plaque was more frequently detected in SLE patients than in NCs (26/102 (25.4%) vs. five of 40 (12.5%), p ¼ 0.012). In addition, the carotid PI of SLE patients (0.68 1.39) was higher than that of NCs (0.26 0.87, p ¼ 0.026). Plaques were most frequent in the bulb portion (PI ¼ 0.92) but rare in the proximal portion of the common carotid artery and the distal portion of the external carotid artery. On correlation analysis, age (b ¼ 0.485, p < 0.001), BMI (b ¼ 0.237, p ¼ 0.003), WHR (b ¼ 0.218, p ¼ 0.007), SLEDAI (b ¼ 0.239,
Table 2 Cardiovascular risk factors and carotid intima-media thickness between patients with SLE and normal controls
Age, years Body mass index, kg/m2 Waist-hip ratio Smoker, n (%) Hypertension, n (%) Diabetes mellitus, n (%) Family history of CVD, n (%) Postmenopausal, n (%) Carotid IMT, mm Carotid plaque index Vitamin D (25(OH)D3), ng/ml
SLE (n ¼ 102)
NC (n ¼ 52)
p value
38.8 7.0 21.1 2.8 0.81 0.06 3 (2.94) 4 (3.92) 0 22 (21.56) 10 (9.8) 0.41 0.08 0.68 1.39 12.1 7.4
38.1 8.7 21.8 2.5 0.8 0.07 0 2 (3.8) 0 16 (30.7) 6 (11.5) 0.32 0.08 0.26 0.87 11.0 3.1
0.058 0.865 0.364 0.213 0.510 NS 0.163 0.073 0.012 0.026 0.841
SLE: systemic lupus erythematosus; NC: normal controls; CVD: cardiovascular disease; NS: not significant; IMT: intima media thickness. Lupus
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Carotid subclinical atherosclerosis and vitamin D in SLE J-Y Jung et al.
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Table 3 Correlation with carotid intima-media thickness in SLE patients
Age, years Body mass index, kg/m2 Waist-hip ratio Total cholesterol, mg/dl LDL cholesterol, mg/dl HDL cholesterol, mg/dl Triglyceride, mg/dl ESR, mm/hour CRP, mg/dl Complement 3, mg/dl Complement 4, mg/dl Anti-dsDNA antibody, (þ) Anticardiolipin antibody, (þ) Lupus anticoagulant, (þ) Disease duration, months SLEDAI Arthritis Renal involvement Taking aspirin Accumulated steroid dose, g Statin use Vitamin D (25(OH)D3), ng/ml
Correlation coefficient
p
0.485 0.237 0.218 0.037 0.116 0.142 0.076 0.002 0.095 0.03 0.053 0.017 0.017 0.033 0.042 0.239 0.124 0.033 0.244 0.101 0.08 0.073
CONCISE REPORT
Carotid subclinical atherosclerosis is associated with disease activity but not vitamin D in Korean systemic lupus erythematosus J-Y Jung, B-R Koh, C-B Bae, H-A Kim and C-H Suh Department of Rheumatology and BK21 Division of Cell Transformation and Restoration, Ajou University School of Medicine, Suwon, Korea
Atherosclerosis develops early in systemic lupus erythematosus (SLE) patients and is an important cause of mortality. Vitamin D deficiency is found to be associated with cardiovascular disease and autoimmunity. We evaluated the extent of carotid subclinical atherosclerosis and analyzed its correlation with vitamin D in SLE. One hundred and two female patients with SLE and 52 normal controls (NCs) were recruited. The mean carotid intima-media thickness (IMT) of SLE patients was 0.41 0.08 mm, which was higher than that of NCs (0.32 0.08 mm, p ¼ 0.012). In addition, carotid plaques were more frequent and the plaque index was higher in SLE patients than in NCs (0.68 1.39 vs. 0.26 0.87, p ¼ 0.026). Carotid IMT was correlated with age, body mass index, SLE disease activity index, and aspirin use in SLE patients. The plaque index was correlated with renal involvement. Vitamin 25(OH)D3 level was not correlated with carotid IMT, plaque index or disease activity markers. In SLE, the risk of cardiovascular disease is higher than that in NCs, which may be derived from systemic inflammation. It may be not suitable to assess vitamin D as a marker of disease activity or subclinical atherosclerosis in SLE patients. Lupus (2014) 23, 1517–1522. Key words: Systemic lupus erythematosus; atherosclerosis; carotid artery; disease activity; vitamin D
Introduction Systemic lupus erythematosus (SLE) is a chronic disease arising from autoimmune dysregulation with diverse manifestations. It is well known that patients with SLE develop cardiovascular disease (CVD) frequently and early, which is a common cause of death.1 This phenomenon might be related to chronic inflammation, existence of autoantibodies, pathologic endothelial activation and prolonged immunosuppressive therapy, as it is not explained by traditional risk factors alone. Measurements of carotid artery intima-media thickness (IMT) and carotid artery plaque by Doppler ultrasound are useful and reliable for predicting CVD risk, and are also used as atherosclerosis prescreening tools.2
Correspondence to: Chang-Hee Suh, Department of Rheumatology and BK21 Division of Cell Transformation and Restoration Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu Suwon, Korea 443-380. Email: [email protected] Received 28 September 2013; accepted 30 June 2014
Vitamin D is synthesized in the skin following ultraviolet B exposure, with approximately 20% of the required vitamin D exogenously acquired from foods or supplements. Although 1,25(OH)2D3 is the main effector molecule, it is useful to check 25(OH)D3, which has a long halflife, to assess the vitamin D status. Currently, immunoradiometric assay is commonly used in estimating level of 25(OH)D3. Vitamin D affects malignancies, autoimmune diseases, infections and CVD.3 In the cardiovascular system, vitamin D deficiency causes endothelial dysfunction resulting in decreased vasodilation, a proinflammatory and prothrombotic state, and increased arterial stiffness.4 In the immune system, 1,25(OH)2D3 interacts and activates immune cells to release cytokines and transfers specific signals as an immune modulator. As vitamin D deficiency is common in SLE patients, vitamin D supplementation is expected to improve immune dysregulation.5 In this study, carotid IMT and carotid plaques were measured in patients with SLE and these factors were assessed in association with traditional risk factors for CVD and disease-related risk factors of SLE. The level of 25(OH)D3 was also
! The Author(s), 2014. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav
Downloaded from lup.sagepub.com at UCSF LIBRARY & CKM on May 13, 2015
10.1177/0961203314544185
Carotid subclinical atherosclerosis and vitamin D in SLE J-Y Jung et al.
1518
checked and evaluated as a marker of disease activity or CVD.
Methods Subject recruitment A total of 102 female SLE patients who visited the rheumatology outpatient clinic of Ajou University Hospital, and 52 age-matched healthy female normal controls (NCs), aged above 18 years, were recruited. All SLE patients met the diagnostic criteria of the American College of Rheumatology (ACR)6 and the patients were excluded if they had CVD, malignancy, chronic renal failure, or were pregnant. The traditional risk factors for CVD, which had been established to be able to predict further cardiovascular events, were assessed by chart review or participant interviews. None of the NC subjects had clinical evidence of myocardial infarction or cerebrovascular disease. Family history was defined as premature CVD before 55 years of age among first-degree male relatives or before 65 years of age among female relatives. Smoking status was defined as present if the subject smoked for more than 20 years despite cessation at the time of recruitment. The body mass index (BMI), calculated by height and weight, and the waist-hip ratio (WHR) of all participants were measured. Comprehensive medication histories, including corticosteroids, immunosuppressants, and anticoagulants, were obtained through patient interviews and chart reviews. All participants provided written informed consent. The study protocol was approved by the institutional review board of our hospital. Laboratory testing and disease activity assessment Laboratory testing included routine chemical analyses, complete blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), lipoprotein (Lp), and complement (C3 and C4). Additionally, autoantibody results were recorded, including those for antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA) antibody, anticardiolipin antibody (aCL) and lupus anticoagulant (LA). Vitamin D (25(OH)D3) levels were detected by immunoradiometric assay using the Bio-Line 25(OH)D3-Ria CT kit (Bio-Line S.A., Brussels, Belgium), according to the manufacturer’s instructions. The levels of 25(OH)D3 were detected around the same time during winter, from December to February. The season of detecting
must be the same because vitamin D synthesized in the skin changes seasonally because of different ultraviolet B (UVB) exposure. Clinical manifestations including arthritis, rash and renal involvement and the drug records of the patients were collected at the time carotid IMT and plaque were measured. Disease activity and disease-related damage were assessed at the time of enrollment using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)6 and Systemic Lupus International Collaborating Clinics/ACR Damage Index (SLICC/ACR DI), respectively. Measurement of carotid IMT and carotid plaque As biomarkers of subclinical atherosclerosis, carotid IMT and carotid plaques were measured using the 11 MHz linear transducer of Logiq P6 Pro (GE, Fairfield, CT, USA). Using B mode scanning the right and left common carotid arteries were scanned longitudinally and the bifurcation of the carotid artery was checked, then the calculated means of three portions were measured at 10 mm intervals from 10 mm upwards. Values from each side were then averaged to produce an overall measurement of the carotid IMT.6 Abnormal IMT was defined as the mean plus two standard deviations of the NC value. Carotid artery plaques were measured and the plaque index (PI) was calculated as previously described.7 The degree of plaque was graded 0 as no observed plaque; 1 as one small plaque (50%) or multiple plaques with medium plaque. The degrees measured at seven divided segments were summed. To minimize inter-observer-related bias, each test was performed by one investigator who was blinded to the clinical data. The intra-observer variability was 2.8%. Statistical analysis Demographic features, carotid IMT, carotid PI and 25(OH)D3 levels in the SLE and the NCs were compared using the Mann-Whitney U-test (non-parametric test). Also, carotid IMT, carotid PI and SLE-related markers between groups that were divided by 25(OH)D3 were compared using the Mann-Whitney U-test. The correlation carotid IMT with cardiovascular risk factors and SLE-related markers were determined using Spearman’s correlation coefficient. Two-sided p values of less than 0.05 were considered statistically significant. Statistical analysis was performed using version 12.0.1 of the Statistical Package for
Lupus Downloaded from lup.sagepub.com at UCSF LIBRARY & CKM on May 13, 2015
Carotid subclinical atherosclerosis and vitamin D in SLE J-Y Jung et al.
1519
the Social Sciences (SPSS; SPSS Inc, Chicago, IL, USA).
Results Characteristics of SLE patients and controls The characteristics and cardiovascular risk factors of the SLE patients and NCs are shown in Tables 1 and 2. In patients with SLE, 44 patients (43.1%) had arthritis, 17 patients (16.7%) had oral ulcers, and 14 patients (13.7 %) had lupus nephritis Table 1 Clinical characteristics and biochemical assessments of patients with SLE (n ¼ 102) Mean SD or n (%) Oral ulcer Malar rash Alopecia Arthritis Photosensitivity Renal disease Hemoglobin, g/dl Leukocyte, /ml Lymphocyte, /ml Platelet, 103/ ml ESR, mm/hour CRP, mg/dl Complement 3, mg/dl Complement 4, mg/dl Vitamin D (25(OH)D3), ng/ml Total cholesterol, mg/dl Triglyceride, mg/dl HDL, mg/dl LDL, mg/dl Dyslipidemia Anti-dsDNA antibody Anticardiolipin antibody Lupus anticoagulant Disease duration, months SLEDAI score Hydroxychloroquine use NSAID use Azathioprine use Cyclophosphamide use Mycophenolate mofetil use Aspirin use Statin use ACEI or ARB use Steroid use Steroid current dose, g Steroid cumulative dose, g
16 (15.7) 15 (14.7) 17 (16.7) 44 (43.1) 6 (5.9) 14 (13.7) 12.4 1.4 5,546 2,037 1,615 788 217 67.4 21.6 18.4 0.14 0.27 99.5 27.3 20.03 8.02 12.7 8.6 157.5 31.5 99.4 65.6 53.7 14.1 83.9 25.3 11 (10.7) 37 (36.3) 24 (23.5) 9 (8.8) 78.0 52.9 4.4 3.0 97 (95.1) 31 (30.4) 10 (9.8) 6 (5.8) 8 (7.8) 16 (15.7) 4 (3.7) 17 (16.7) 75 (73.5) 2.6 3.1 11.3 19
SLE: systemic lupus erythematosus; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; HDL: high-density lipoprotein; LDL: low-density lipoprotein; dsDNA: doublestranded deoxyribonucleic acid; SLEDAI: systemic lupus erythematosus disease activity index; NSAID: non-steroidal anti-inflammatory drugs; ACEI: angiotensin-converting enzyme inhibitor; ARB: angiotensin receptor blocker.
(Table 1). All patients had ANA, 37 patients (36.3%) had anti-dsDNA antibodies, 24 patients (23.5%) had aCL, and nine patients (8.8 %) had LA. The disease duration was 78.0 52.9 months, the SLEDAI value was 4.4 3.0, and only three patients had SLICC/ACR DI score 1. Ninetyseven patients (95.1%) took hydroxychloroquine, 15 patients (14.7%) took aspirin, and 75 patients (73.5%) took corticosteroids. The current corticosteroid dose was 2.6 3.1 mg, and the accumulated corticosteroids dose was 11.3 19.0 g of a prednisone equivalent. The BMI of patients with SLE was 21.1 2.8 (kg/m2) and the WHR was 0.81 0.06, which did not differ from those of NCs (21.8 2.5 kg/m2 and 0.8 0.07, respectively) (Table 2). Correlations between carotid IMT, carotid plaque, cardiovascular risk factors and clinical features The mean carotid IMT of SLE patients was 0.41 0.08 mm, which was higher than that of NCs (0.32 0.08 mm, p ¼ 0.012) (Table 2). And 23 patients (22.5%) showed significantly abnormal carotid IMT, which was more than 0.59 mm. Carotid plaque was more frequently detected in SLE patients than in NCs (26/102 (25.4%) vs. five of 40 (12.5%), p ¼ 0.012). In addition, the carotid PI of SLE patients (0.68 1.39) was higher than that of NCs (0.26 0.87, p ¼ 0.026). Plaques were most frequent in the bulb portion (PI ¼ 0.92) but rare in the proximal portion of the common carotid artery and the distal portion of the external carotid artery. On correlation analysis, age (b ¼ 0.485, p < 0.001), BMI (b ¼ 0.237, p ¼ 0.003), WHR (b ¼ 0.218, p ¼ 0.007), SLEDAI (b ¼ 0.239,
Table 2 Cardiovascular risk factors and carotid intima-media thickness between patients with SLE and normal controls
Age, years Body mass index, kg/m2 Waist-hip ratio Smoker, n (%) Hypertension, n (%) Diabetes mellitus, n (%) Family history of CVD, n (%) Postmenopausal, n (%) Carotid IMT, mm Carotid plaque index Vitamin D (25(OH)D3), ng/ml
SLE (n ¼ 102)
NC (n ¼ 52)
p value
38.8 7.0 21.1 2.8 0.81 0.06 3 (2.94) 4 (3.92) 0 22 (21.56) 10 (9.8) 0.41 0.08 0.68 1.39 12.1 7.4
38.1 8.7 21.8 2.5 0.8 0.07 0 2 (3.8) 0 16 (30.7) 6 (11.5) 0.32 0.08 0.26 0.87 11.0 3.1
0.058 0.865 0.364 0.213 0.510 NS 0.163 0.073 0.012 0.026 0.841
SLE: systemic lupus erythematosus; NC: normal controls; CVD: cardiovascular disease; NS: not significant; IMT: intima media thickness. Lupus
Downloaded from lup.sagepub.com at UCSF LIBRARY & CKM on May 13, 2015
Carotid subclinical atherosclerosis and vitamin D in SLE J-Y Jung et al.
1520
Table 3 Correlation with carotid intima-media thickness in SLE patients
Age, years Body mass index, kg/m2 Waist-hip ratio Total cholesterol, mg/dl LDL cholesterol, mg/dl HDL cholesterol, mg/dl Triglyceride, mg/dl ESR, mm/hour CRP, mg/dl Complement 3, mg/dl Complement 4, mg/dl Anti-dsDNA antibody, (þ) Anticardiolipin antibody, (þ) Lupus anticoagulant, (þ) Disease duration, months SLEDAI Arthritis Renal involvement Taking aspirin Accumulated steroid dose, g Statin use Vitamin D (25(OH)D3), ng/ml
Correlation coefficient
p
0.485 0.237 0.218 0.037 0.116 0.142 0.076 0.002 0.095 0.03 0.053 0.017 0.017 0.033 0.042 0.239 0.124 0.033 0.244 0.101 0.08 0.073
