Background
Methods
Study participants
Data collection
Lipids and cholesterol efflux assessments
Carotid ultrasound assessment
Statistical analysis
Control subjects (n = 223) | Patients with RA (n = 178) |
p Value | |
---|---|---|---|
Age, years | 59 ± 9 | 55 ± 11 |
0.000
|
Female sex, n (%) | 155 (70) | 140 (79) | 0.063 |
Body mass index, kg/m2
| 28 ± 5 | 28 ± 5 | 0.74 |
Abdominal circumference, cm | 93 ± 14 | 97 ± 13 |
0.006
|
Systolic blood pressure, mmHg | 133 ± 15 | 137 ± 19 |
0.018
|
Diastolic blood pressure, mmHg | 82 ± 10 | 83 ± 12 | 0.36 |
Cardiovascular comorbidity | |||
Smoking, n (%) | 45 (20) | 29 (16) | 0.29 |
Diabetes, n (%) | 10 (4) | 27 (15) |
0.000
|
Hypertension, n (%) | 64 (29) | 62 (35) | 0.22 |
Dyslipidemia, n (%) | 41 (18) | 71 (40) |
0.000
|
Antihypertensive treatment, n (%) | 38 (17) | 63 (35) |
0.000
|
Statins, n (%) | 22 (10) | 60 (34) |
0.000
|
Hormone replacement therapy, n (%) | 7 (3) | 0 (0) |
0.018
|
Laboratory examinations, including lipid profile | |||
ESR, mm/h | 10 ± 8 | 35 ± 22 |
0.000
|
CRP, mg/dl | 1.0 (1.0–3.0) | 3.3 (1.6–6.1) | 0.34 |
Cholesterol, mg/dl | 218 ± 39 | 206 ± 37 |
0.001
|
Triglycerides, mg/dl | 105 ± 52 | 151 ± 92 |
0.000
|
HDL cholesterol, mg/dl | 63 ± 17 | 56 ± 16 |
0.000
|
LDL cholesterol, mg/dl | 134 ± 36 | 120 ± 33 |
0.000
|
Lipoprotein A, mg/dl | 16 (9–35) | 33 (10–121) |
0.000
|
Apolipoprotein A, mg/dl | 191 ± 35 | 170 ± 28 |
0.000
|
Apolipoprotein B, mg/dl | 102 ± 24 | 109 ± 59 | 0.13 |
ApoB/ApoA ratio | 0.55 ± 0.16 | 0.65 ± 0.29 |
0.000
|
Atherogenic index | 3.72 ± 1.14 | 4.02 ± 1.51 |
0.036
|
Cholesterol efflux capacity, % | 16.9 ± 10.4 | 18.9 ± 9.0 | 0.11 |
Rheumatoid arthritis-related data | |||
Disease duration, years | 7 (4–15) | ||
Age at onset, years | 45 ± 13 | ||
DAS28 | 3.74 ± 1.19 | ||
Remission, n (%) | 38 (21) | ||
Low activity, n (%) | 29 (16) | ||
Moderate activity, n (%) | 84 (47) | ||
High activity, n (%) | 27 (15) | ||
DAS28-CRP | 2.94 ± 0.99 | ||
SDAI | 14 (8–21) | ||
CDAI | 82 (40–112) | ||
Rheumatoid factor, n (%) | 119 (67) | ||
ACPA, n (%) | 98 (55) | ||
Prednisone intake, n (%) | 62 (35) | ||
Prednisone dose, mg/day | 5 (3–6) | ||
NSAIDs, n (%) | 78 (44) | ||
DMARDs, n (%) | 153 (86) | ||
Methotrexate, n (%) | 135 (76) | ||
Leflunomide, n (%) | 19 (11) | ||
Biologic therapy, n (%) | 41 (23) | ||
Anti-TNF-α therapy, n (%) | 23 (13) | ||
Tocilizumab, n (%) | 11 (6) | ||
Rituximab, n (%) | 5 (3) | ||
Abatacept, n (%) | 2 (1) | ||
Carotid assessments | |||
CIMT, mm | 0.671 ± 0.143 | ||
Carotid plaque, n (%) | 66 (37) |
Results
Demographic, laboratory, and disease-related data
Relationship of CEC with demographic, traditional cardiovascular risk factors, and disease-related data in patients and control subjects
Control subjects | Patients with RA | |||
---|---|---|---|---|
Percent efflux β coefficient (95% CI) |
p Value | Percent efflux β coefficient (95% CI) |
p Value | |
Age, years | −0.9 (−0.4 to 0.2) | 0.50 | −0.2 (−0.2 to 0.1) | 0.78 |
Male sex | −0.9 (−4.6 to 2.8) | 0.62 | −6.1 (−9.4 to 2.8) |
0.000
|
Body mass index | −0.2 (−0.6 to 0.1) | 0.20 | 0.2 (−0.1 to 0.5) | 0.21 |
Abdominal circumference | −0.1 (−0.2 to 0.0) | 0.058 | 0.0 (−0.1 to 0.2) | 0.42 |
Systolic blood pressure |
−0.1 (−0.2 to 0.0)
|
0.025
| 0.1 (−0.0 to 0.2) | 0.11 |
Diastolic blood pressure | −0.0 (-0.1 to 0.0) | 0.29 | 0.01 (−0.0 to 0.2) | 0.15 |
Cardiovascular comorbidities | ||||
Smoking | 1.8 (−2.4 to 6.0) | 0.40 | −0.3 (−4.5 to 3.9) | 0.89 |
Diabetes | 1.2 (−5.9 to 8.3) | 0.74 | 2.9 (−1.3 to 7.2) | 0.17 |
Hypertension | −2.4 (−6.0 to 1.1) | 0.17 | 0.1 (−3.0 to 3.2) | 0.95 |
Dyslipidemia | −1.1 (−5.2 to 3.1) | 0.61 | −0.3 (−3.4 to 2.8) | 0.85 |
Antihypertensive treatment | 0.7 (−3.6 to 5.0) | 0.75 | 0.4 (−2.7 to 3.5) | 0.80 |
Statins | −2.1 (−7.4 to 3.2) | 0.44 | 0.6 (−2.6 to 3.8) | 0.70 |
Laboratory examinations, including lipid profile | ||||
ESR | −0.2 (−0.1 to 0.1) | 0.23 | −0.1 (−0.1 to 0.0) | 0.12 |
CRP | −0.3 (−0.6 to 0.0) | 0.092 | −0.0 (−0.1 to 0.1) | 0.83 |
Cholesterol | 0.0 (−0.0 to 0.1) | 0.11 | 0.00 (−0.0 to 0.00) | 0.69 |
Triglycerides | −0.0 (−0.1 to 0.0) | 0.19 | 0.0 (−0.0 to 0.0) | 0.30 |
HDL cholesterol | 0.1 (−0.0 to 0.2) | 0.092 | 0.0 (−0.1 to 0.1) | 0.48 |
LDL cholesterol | 0.0 (−0.0 to 0.1) | 0.32 | −0.0 (−0.1 to 0.0) | 0.62 |
Lipoprotein A | 0.1 (−0.0 to 0.1) | 0.059 | −0.0 (−0.0 to 0.0) | 0.35 |
Apolipoprotein A | 0.0 (−0.0 to 0.1) | 0.089 | −0.0 (−0.1 to 0.0) | 0.84 |
Apolipoprotein B | 0.0 (−0.1 to 0.1) | 0.77 | 0.00 (−0.0 to 0.0) | 0.99 |
ApoB/ApoA ratio | −5.8 (−16.8 to 5.4) | 0.31 | 0.8 (−4.1 to 5.7) | 0.76 |
Atherogenic index | 0.7 (−2.4 to 1.0) | 0.41 | 0.0 (−1 to 1) | 0.99 |
Rheumatoid arthritis-related data | ||||
Disease duration | 0.1 (−0.0 to 0.3) | 0.12 | ||
DAS28 | −1.1 (−2.3 to 0.2) | 0.086 | ||
Remission | – | |||
Low disease activity |
−5.2 (−10.0 to 0.3)
|
0.039
| ||
Moderate disease activity |
−4.6 (−8.5 to 0.7)
|
0.020
| ||
High disease activity | −3.2 (−8.1 to 1.7) | 0.19 | ||
Moderate and high disease activity | −4.2 (−7.9 to 0.6)
|
0.024
| ||
DAS28-CRP | −1.1 (−2.7 to 0.4) | 0.14 | ||
SDAI | −0.0 (−0.1 to 0.1) | 0.54 | ||
CDAI | −0.0 (−0.0 to 0.0) | 0.31 | ||
Rheumatoid factor | −0.4 (−3.8 to 2.9) | 0.81 | ||
ACPA | 0.4 (−2.7 to 3.6) | 0.78 | ||
Prednisone intake | −0.3 (−3.4 to 2.9) | 0.88 | ||
Prednisone dose | −0.3 (−3.4 to 2.9) | 0.88 | ||
NSAIDs |
4.6 (1.5 to 7.6)
|
0.004
| ||
DMARDs | −0.2 (−4.6 to 4.2) | 0.93 | ||
Methotrexate | 0.5 (−2.9 to 4.0) | 0.77 | ||
Leflunomide | −1.3 (−5.9 to 3.3) | 0.58 | ||
Biologic therapy | 3.57 (−0.0 to 7.2) | 0.052 | ||
Anti-TNF-α therapy | 0.7 (−4.0 to 5.5) | 0.76 | ||
Tocilizumab |
8.0 (2.3 to 13.7)
|
0.007
| ||
Rituximab | 1.3 (−9.1 to 11.7) | 0.81 | ||
Abatacept | −1.4 (−14.1 to 11.4) | 0.83 |
Relationship of RA patient characteristics with CIMT and carotid plaques
Carotid plaque | CIMT (×10 mm) | |||
---|---|---|---|---|
Patients with RA (n = 178) | OR (95% CI) |
p Value | β Coefficient (95% CI) |
p Value |
Age | 1.15 (1.10–1.20) |
0.000
| 0.08 (0.01–0.01) |
0.000
|
Male sex | 3.00 (1.44–6.26) |
0.003
| 1.1 (0.6–1.6) |
0.000
|
Body mass index | 1.00 (0.95–1.06) | 0.92 | 0.03 (0.02–0.07) | 0.23 |
Abdominal circumference | 1.01 (0.99–1.04) | 0.31 | 0.02 (0.00–0.03) |
0.021
|
Systolic blood pressure | 1.04 (1.02–1.06) |
0.000
| 0.04 (0.03–0.05) |
0.000
|
Diastolic blood pressure | 1.02 (0.997–1.05) | 0.078 | 0.02 (0.01–0.04) |
0.009
|
Cardiovascular comorbidity | ||||
Smoking | 1.04 (0.46–2.37) | 0.92 | −0.1 (0.7 to 0.4) | 0.63 |
Diabetes | 3.54 (1.51–8.30) |
0.004
| 1.0 (0.04 to 1.6) |
0.001
|
Hypertension | 2.57 (1.36–4.87) |
0.004
| 0.6 (0.2 to 1.1) |
0.005
|
Dyslipidemia | 3.61 (1.91–6.84) |
0.000
| 0.4 (−0.01 to 0.8) | 0.082 |
Antihypertensive treatment | 2.73 (1.44–5.18) |
0.002
| 0.7 (0.2 to 1.1) |
0.002
|
Statins | 3.93 (2.04–7.58) |
0.000
| 0.5 (0.0 to 0.9) |
0.036
|
Laboratory including lipid profile | ||||
ESR | 1.02 (1.01–1.04) |
0.003
| 0.01 (0.00 to 0.02) |
0.041
|
CRP | 0.45 (0.96–1.02) | 0.45 | 0.00 (−0.01 to 0.01) | 0.947 |
Cholesterol | 1.00 (0.99–1.01) | 0.83 | 0.00 (0.00 to 0.01) | 0.16 |
Triglycerides | 1.00 (0.99–1.01) | 0.13 | 0.00 (0.00 to 0.00) |
0.034
|
HDL cholesterol | 0.99 (0.98–1.01) | 0.51 | −0.01 (−0.03 to 0.00) |
0.034
|
LDL cholesterol | 0.99 (0.99–1.01) | 0.77 | 0.00 (0.00 to 0.01) | 0.14 |
Lipoprotein A | 1.00 (1.00–1.01) |
0.043
| 0.00 (0.00 to 0.00) | 0.76 |
Apolipoprotein A | 1.01 (0.99–1.02) | 0.37 | 0.00 (−0.01 to 0.01) | 0.80 |
Apolipoprotein B | 0.99 (0.99–1.01) | 0.73 | 0.00 (0.00 to 0.00) | 0.48 |
ApoB/ApoA ratio | 0.70 (0.21–2.33) | 0.56 | 0.4 (0.4 to 1.1) | 0.36 |
Atherogenic index | 1.06 (0.87–1.29) | 0.57 | 0.2 (0.0 to 0.3) |
0.029
|
Rheumatoid arthritis-related data | ||||
Disease duration | 1.02 (0.99–1.06) | 0.17 | 0.01 (−0.01 to 0.03) | 0.41 |
DAS28 | 1.36 (1.05–1.77) |
0.022
| 0.12 (−0.06 to 0.30) | 0.18 |
DAS28-CRP | 1.19 (0.88–1.63) | 0.26 | 0.08 (−0.14 to 0.29) | 0.47 |
SDAI | 0.99 (0.98–1.02) | 0.85 | 0.00 (−0.01 to 0.01) | 0.76 |
CDAI | 1.01 (1.00–1.01) |
0.055
| 0.00 (0.00 to 0.01) | 0.16 |
Rheumatoid factor | 0.87 (0.45–1.71) | 0.69 | −0.5 (−1.0 to 0.0) |
0.043
|
ACPA | 0.87 (0.46–1.63) | 0.66 | −0.3 (−0.8 to 0.1) | 0.14 |
Prednisone intake | 1.11 (0.59–2.10) | 0.74 | 0.0 (−0.4 to 0.5) | 0.90 |
Prednisone doses | 0.99 (0.89–1.09) | 0.81 | −0.04 (−0.1 to 0.2) | 0.20 |
NSAIDs | 0.40 (0.21–0.76) |
0.005
| −0.6 (−1.0 to 0.2) |
0.005
|
DMARDs | 2.04 (0.77–5.41) | 0.15 | 0.3 (−0.4 to 0.9) | 0.43 |
Methotrexate | 0.77 (0.38–1.54) | 0.46 | −0.3 (−0.8 to 0.2) | 0.25 |
Leflunomide | 2.04 (0.78–5.32) | 0.14 | 0.9 (0.2 to 1.6) |
0.010
|
Biologic therapy | 0.51 (0.23–1.13) | 0.098 | −0.2 (−0.8 to 0.3) | 0.35 |
Anti-TNF-α therapy | 0.89 (0.36–2.23) | 0.81 | 0.4 (−0.3 to 1.0) | 0.23 |
Tocilizumab | 0.16 (0.02–1.26) | 0.081 | −0.7 (−1.6 to 0.1) | 0.085 |
Rituximab | 0.42 (0.05–3.80) | 0.44 | −1.1 (−2.4 to 0.1) | 0.81 |
Abatacept | 1.71 (0.11–27.8) | 0.71 | 0.6 (−1.4 to 2.6) | 0.55 |
CEC’s association with carotid subclinical atherosclerosis in patients with RA
Carotid plaque | CIMT (×10 mm) | |||
---|---|---|---|---|
Cholesterol efflux capacity | OR (95% CI) |
p
| β Coefficient (95% CI) |
p
|
Unadjusted |
0.95 (0.92–0.99)
|
0.023
| 0.01 (−0.02 to 0.03) | 0.67 |
Adjusted |
0.94 (0.89–0.98)
|
0.015
| 0.01 (−0.02 to 0.03) | 0.54 |