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Research ArticleArticle

Carotid Plaque Characteristics and Disease Activity in Rheumatoid Arthritis

Anne G. Semb, Silvia Rollefstad, Sella A. Provan, Tore K. Kvien, Einar Stranden, Inge C. Olsen and Jonny Hisdal
The Journal of Rheumatology April 2013, 40 (4) 359-368; DOI: https://doi.org/10.3899/jrheum.120621
Anne G. Semb
From the Department of Rheumatology, Diakonhjemmet Hospital; Section of Vascular Investigations, Oslo Vascular Centre, Oslo University Hospital Aker; and Faculty of Medicine, University of Oslo, Oslo, Norway.
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  • For correspondence: a-semb{at}diakonsyk.no
Silvia Rollefstad
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Sella A. Provan
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Tore K. Kvien
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Einar Stranden
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Inge C. Olsen
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Jonny Hisdal
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  • Number of carotid plaques in patients with rheumatoid arthritis (RA) and non-RA controls; carotid plaques shown as percentage of total number of patients and controls. Difference between groups: Poisson regression adjusted for age and sex, p < 0.001.
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    Figure 1

    Number of carotid plaques in patients with rheumatoid arthritis (RA) and non-RA controls; carotid plaques shown as percentage of total number of patients and controls. Difference between groups: Poisson regression adjusted for age and sex, p < 0.001.

  • Characteristics of carotid artery plaque according to disease activity in patients with rheumatoid arthritis (RA) and controls. Different methods were used to compare patients and controls and trend within RA disease activity: mixed models with random intercepts were used to analyze plaque area and GSM; Poisson regression analysis was used to compare number of plaques between patients and controls. All data were adjusted for age, sex, smoking, and systolic blood pressure and are presented as least-square means with standard error. Trend analyses were performed by linear contrasts within each model. #RA vs controls; †trend in RA disease activity. CDAI: Clinical Disease Activity Index; SDAI: Simplified Disease Activity Index; DAS28: Disease Activity Score based on 28-joint counts; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; Ctr: controls; Rem: remission; LDA: low disease activity; MDA: moderate disease activity; HDA: high disease activity; GSM: Gray-Scale Median.
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    Figure 2

    Characteristics of carotid artery plaque according to disease activity in patients with rheumatoid arthritis (RA) and controls. Different methods were used to compare patients and controls and trend within RA disease activity: mixed models with random intercepts were used to analyze plaque area and GSM; Poisson regression analysis was used to compare number of plaques between patients and controls. All data were adjusted for age, sex, smoking, and systolic blood pressure and are presented as least-square means with standard error. Trend analyses were performed by linear contrasts within each model. #RA vs controls; †trend in RA disease activity. CDAI: Clinical Disease Activity Index; SDAI: Simplified Disease Activity Index; DAS28: Disease Activity Score based on 28-joint counts; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; Ctr: controls; Rem: remission; LDA: low disease activity; MDA: moderate disease activity; HDA: high disease activity; GSM: Gray-Scale Median.

Tables

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    Table 2

    Characteristics of patients with rheumatoid arthritis according to disease activity measures.

    CDAISDAIDAS28
    RemissionLDAMDA + HDAMDA + HDA vs RemissionRemissionLDAMDA + HDAMDA + HDA vs RemissionRemissionLDAMDA + HDAMDA + HDA vs Remission
    ≤ 2.8> 2.8 and ≤ 10> 10p≤ 3.3> 3.3 and ≤ 11> 11p< 2.6≥ 2.6 and ≤ 3.2> 3.2p
    No. patients437131436834782740
    Age, yrs, median (IQR)64.1 (55.7–72.6)63.5 (54.0–70.9)60.0 (51.0–65.7)0.0761.7 (53.6–69.2)63.5 (54.0–70.9)60.4 (51.7–68.6)0.5362.4 (53.2–70.4)63.5 (54.4–69.8)61.7 (53.6–72.2)0.91
    Sex, female/male30/13 (69.8/30.2)55/17 (76.4/23.6)25/6 (80.6/19.4)0.2931/11 (73.8/26.2)50/18 (73.5/25.5)29/6 (82.9/17.1)0.3455/23 (70.5/29.5)23/5 (82.1/17.9)32/8 (80.0/20.0)0.27
    Cardiovascular risk factors
    Smoking ever-never27 (62.8)50 (69.4)18 (58.1)0.8125 (59.5)48 (70.6)21 (60.0)0.8454 (69.2)17 (60.7)24 (60.0)0.41
    Systolic BP, mm Hg131.3 ± 20.2136.3 ±21.3133.7 ± 18.40.60130.9 ± 20.5134.9 ± 19.8137.1 ± 21.50.20132.1 ± 20.3135.8 ± 18.3137.5 ± 21.80.19
    Diastolic BP, mm Hg79.1 ± 10.080.7 ± 9.681.1 ± 9.30.3879.1 ± 9.780.2 ± 10.181.9 ± 8.60.1879.2 ± 10.282.0 ± 9.381.4 ± 8.50.22
    Diabetes1 (2.3)8 (11.1)4 (12.9)0.081 (2.4)7 (10.3)5 (14.3)0.066 (7.7)1 (3.6)6 (15.0)0.22
    Body mass index, kg/m225.2 ± 3.726.0 ± 5.526.3 ± 4.90.2725.6 ± 4.226.1 ± 5.425.7 ± 4.80.9225.7 ± 4.426.2 ± 6.026.0 ± 5.00.74
    Familial CVD6 (14.0)8 (11.1)4 (12.9)0.985 (11.9)9 (13.2)4 (11.4)0.9910 (12.8)3 (10.7)5 (12.5)0.94
    CVD measures
    CVD3 (7.0)12 (16.7)6 (19.4)0.103 (7.1)11 (16.2)7 (20.0)0.0910 (12.8)2 (7.1)9 (22.5)0.16
    Intima-media thickness, mm0.76 ± 0.160.79 ± 0.200.74 ± 0.180.650.77 ± 0.160.78 ± 0.200.76 ± 0.190.920.77 ± 0.170.76 ± 0.170.78 ± 0.220.80
    Patients with carotid plaques23 (53.5)49 (68.1)14 (45.2)0.4822 (52.4)45 (66.2)18 (51.4)0.9348 (61.5)15 (53.6)23 (57.5)0.67
    No. carotid plaques1.95 ± 0.982.08 ± 0.982.00 ± 1.110.901.86 ± 1.042.04 ± 0.932.17 ± 1.100.381.85 ± 0.902.07 ± 1.032.39 ± 1.080.37
    No. GSM plaques Lipids1.94 ± 1.031.92 ± 0.951.83 ± 0.940.782.00 ± 1.131.82 ± 0.801.94 ± 1.120.881.85 ± 0.911.73 ± 0.902.09 ± 1.060.37
    Total cholesterol6.1 ± 1.35.7 ± 1.25.2 ± 1.10.0016.1 ± 1.25.7 ± 1.35.3 ± 1.10.0065.8 ± 1.45.79 ± 1.15.47 ± 1.10.22
    HDL cholesterol1.8 ± 0.61.8 ± 0.61.7 ± 0.60.381.8 ± 0.61.8 ± 0.61.7 ± 0.50.491.8 ± 0.71.8 ± 0.61.7 ± 0.50.26
    Triglycerides, median (IQR)1.1 (0.8–1.5)1.1 (0.8–1.5)1.1 (0.8–1.7)0.661.1 (0.8–1.5)1.1 (0.8–1.5)1.1 (0.8–1.6)0.821.1 (0.7–1.5)1.1 (0.9 –1.5)1.1 (0.7–1.6)0.69
    LDL cholesterol3.7 ± 1.03.3 ± 1.02.9 ± 1.00.0013.7 ± 1.13.3 ± 1.03.0 ± 1.10.0053.4 ± 1.13.4 ± 1.03.2 ± 1.00.39
    Inflammatory markers
    ESR, mm/h, median (IQR)11.0 (6.0–18.0)13.0 (8.0–26.5)13.0 (5.0–26.0)0.4010.0 (6.8–17.0)13.0 (8.0–25.8)17.0 (6.3–29.0)0.039.0 (6.0–14.0)14.0 (8.0–19.5)26.0 (13.5–34.0)< 0.001
    CRP, mg/dl, median (IQR)2.0 (1.0–4.0)4.0 (2.0–9.0)4.0 (2.0–11.0)0.0032.0 (1.0–3.3)4.0 (2.0–8.0)7.0 (3.0–21.0)< 0.00013.0 (1.0–4.0)3.0 (1.0–8.0)7.5 (3.3–19.0)< 0.001
    • Demographic data are presented as crude data, compared using Student 2-sample T-test, Mann-Whitney U test, and chi-square test as appropriate. Skewed variables were log-transformed. Median values are given as mean ± SD, numbers (%), skewed data as median with interquartile range (IQR). CDAI: Clinical Disease Activity Index; SDAI: Simplified Disease Activity Index; DAS28: Disease Activity Score based on 28-joint counts; LDA: low disease activity; MDA: moderate disease activity; HDA: high disease activity; BP: blood pressure; CVD: cardiovascular disease; GSM: Gray-Scale Median (lipids are mmol/l); HDL: high-density lipoprotein; LDL: low-density lipoprotein; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein.

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    Table 1

    Characteristics of patients with rheumatoid arthritis (RA) and controls.

    CharacteristicRA, n = 152Controls, n = 89p
    Age, yrs, median (IQR)62.7 (53.6, 71.2)55.7 (44.3, 63.1)< 0.001*
    Sex female, n (%)116 (76.3)54 (60.7)0.01
    Cardiovascular risk factors
     Smoking (ever), n (%)97 (63.8)56 (62.9)0.94
     Systolic blood pressure, mm Hg134.5 ± 20.1124.8 ± 18.10.07
     Diastolic blood pressure, mm Hg80.5 ± 9.676.4 ± 10.50.14
     Diabetes, n (%)14 (9.2)2 (2.2)0.12
     Body mass index, kg/m225.9 ± 5.025.4 ± 4.00.25
     Waist circumference, cm88.4 ± 14.186.8 ± 12.70.15
     Familial cardiovascular disease, n (%)19 (12.5)19 (21.3)0.08
    Cardiovascular disease markers
     Intima-media thickness, mm0.8 ± 0.20.7 ± 0.20.39
     Patients with carotid plaque, n (%)90 (59.2)24 (27.0)< 0.001
     No. carotid plaques, median (IQR)1 (0, 2)0 (0, 1)< 0.001
     Area of carotid plaques, mm216.5 ± 8.117.3 + 10.90.77
     Gray-Scale Median value89.3 ± 28.1102.6 + 23.10.12
    Lipids
     Total cholesterol, mmol/l5.7 ± 1.25.8 + 1.00.009
     HDL cholesterol, mmol/l1.8 ± 0.61.7 ± 0.50.11
     Triglycerides, mmol/l, median (IQR)1.1 (0.8, 1.5)1.0 (0.8, 1.5)0.43
     LDL cholesterol, mmol/l3.3 ± 1.13.5 ± 0.90.02
    Inflammatory markers, median (IQR)
     ESR, mm/h13.0 (7.3, 21.8)8.0 (6.0, 15.0)0.21
     CRP, mg/l4.0 (1.0, 8.0)1.0 (1.0, 2.0)< 0.001
    Medication use, n (%)
     Statins27 (17.8)13 (14.6)0.74
     Hypertension medications56 (36.8)18 (20.2)0.40
     DMARD100 (65.85)
     Tumor necrosis factor inhibitors32 (21.1)
     Prednisolone51 (33.6)
     Methotrexate50 (32.9)
    Disease characteristics
     Disease duration, yrs, median (IQR)17 (15, 19)
     Rheumatoid factor-positive, n (%)77 (50.7)
     ACPA-positive, n (%)75 (49.3)
     28 Tender joint count2.3 ± 3.9
     28 Swollen joint count1.9 ± 2.7
     Physician VAS, cm2.5 ± 1.6
     Patient VAS, cm3.3 ± 2.3
     DAS282.6 ± 1.0
     CDAI6.9 ± 6.9
     SDAI7.7 ± 7.3
    • ↵Data are means ± SD unless stated otherwise. P values are adjusted for age and sex using analysis of covariance (continuous variables), logistic regression for dichotomous variables, and Poisson regression for counts. Values for erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and triglycerides were log-transformed for p value calculation. * Mann-Whitney U test (unadjusted). DMARD: disease-modifying antirheumatic drugs; ACPA: anticitrullinated protein antibodies; VAS: visual analog scale for disease activity; DAS:28: Disease Activity Score based on 28-joint count; IQR: interquartile range; HDL: high-density lipoprotein; LDL: low-density lipoprotein; CDAI: Clinical Disease Activity Index; SDAI: Simplified Disease Activity Index.

  • ControlsPatients with RA
    MeasureRemissionLDAMDA + HDAp, RA vs ControlsTrend in RA Disease Activity
    0.39 (0.19)CDAI0.74 (0.17)0.99 (0.13)0.82 (0.20)< 0.00010.65
    0.38 (0.19)SDAI0.75 (0.17)0.95 (0.14)0.88 (0.19)< 0.00010.48
    0.38 (0.19)DAS280.85 (0.13)0.84 (0.20)0.96 (0.17)< 0.00010.47
    0.38 (0.19)CRP0.78 (0.15)0.97 (0.15)0.89 (0.19)< 0.00010.54
    0.38 (0.19)ESR0.91 (0.16)0.70 (0.17)1.01 (0.15)< 0.00010.54
    • CDAI: Clinical Disease Activity Index, SDAI: Simplified Disease Activity Index; DAS28: Disease Activity Score based on 28-joint counts; LDA: low disease activity; MDA: moderate disease activity; HDA: high disease activity; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein.

  • ControlsPatients with RA
    MeasureRemissionLDAMDA + HDAp, RA vs ControlsTrend in RA Disease Activity
    GSM94.69 (6.80)CDAI96.09 (6.31)89.33 (4.52)74.78 (7.44)0.350.03
    94.35 (6.71)SDAI84.71 (6.51)93.74 (4.59)75.78 (6.77)0.33
    94.96 (6.72)DAS2890.84 (4.65)101.82 (7.96)78.91 (5.48)0.09
    95.78 (7.05)CRP84.89 (5.25)88.13 (6.14)93.40 (7.14)0.31
    96.41 (7.18)ESR90.12 (6.96)86.80 (7.26)88.72 (4.89)0.87
    Minimum GSM88.38 (6.64)CDAI89.50 (7.09)78.55 (5.11)65.99 (8.17)0.03
    88.01 (6.64)SDAI78.18 (7.34)84.07 (5.27)66.13 (7.48)0.230.24
    88.11 (6.58)DAS2881.31 (5.23)94.23 (8.73)68.65 (6.22)0.11
    89.33 (7.03)CRP74.50 (6.05)82.94 (6.55)79.13 (8.38)0.63
    89.33 (7.09)ESR81.63 (7.32)79.64 (7.99)77.18 (5.71)0.63
    In area2.82 (0.12)CDAI2.62 (0.11)2.75 (0.08)2.80(0.13)0.27
    2.82 (0.12)SDAI2.74 (0.11)2.67 (0.08)2.85 (0.12)0.530.50
    2.81 (0.12)DAS282.67 (0.08)2.83 (0.14)2.77 (0.09)0.41
    2.78 (0.12)CRP2.85 (0.09)2.59 (0.10)2.68 (0.12)0.23
    2.83 (0.12)ESR2.87 (0.12)(0.12) 2.682.67 (0.08)0.54
    • CDAI: Clinical Disease Activity Index; SDAI: Simplified Disease Activity Index; DAS28: Disease Activity Score based on 28-joint counts; LDA: low disease activity; MDA: moderate disease activity; HDA: high disease activity; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein.

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Carotid Plaque Characteristics and Disease Activity in Rheumatoid Arthritis
Anne G. Semb, Silvia Rollefstad, Sella A. Provan, Tore K. Kvien, Einar Stranden, Inge C. Olsen, Jonny Hisdal
The Journal of Rheumatology Apr 2013, 40 (4) 359-368; DOI: 10.3899/jrheum.120621

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Carotid Plaque Characteristics and Disease Activity in Rheumatoid Arthritis
Anne G. Semb, Silvia Rollefstad, Sella A. Provan, Tore K. Kvien, Einar Stranden, Inge C. Olsen, Jonny Hisdal
The Journal of Rheumatology Apr 2013, 40 (4) 359-368; DOI: 10.3899/jrheum.120621
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Keywords

RHEUMATOID ARTHRITIS
CARDIOVASCULAR DISEASE
ATHEROSCLEROSIS
CAROTID PLAQUE
GRAY-SCALE MEDIAN

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