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Original Article
Effect of Rheumatoid Factor on Vascular Stiffness in General Population without Joint Symptoms
Ji Hyun Lee1, Hee Sang Tag2, Geun Tae Kim2, Min Jeong Kim3, Seung Geun Lee4, Eun Kyung Park4, Dong Wa Koo4
Kosin Medical Journal 2017;32(1):25-35.
DOI: https://doi.org/10.7180/kmj.2017.32.1.25
Published online: January 19, 2017

1Division of Rheumatology, Department of Internal Medicine, Maryknoll Medical Center, Busan, Korea

2Division of Rheumatology, Department of Internal Medicine, College of Medicine, Kosin University, Busan, Korea

3Department of Neurology, College of Medicine, Kosin University, Busan, Korea

4Division of Rheumatology, Department of Internal Medicine, Pusan National University Hospital, Busan, Korea

Corresponding Author: Geun Tae Kim, Division of Rheumatology, Department of Internal Medicine, College of Medicine, Kosin University, 262, Gamcheon-ro, Seo-gu, Busan 49267, Korea Tel: +82-51-990-6415 Fax: +82-51-990-3010 E-mail: gtah@hanmail.net
• Received: July 9, 2015   • Accepted: September 21, 2015

Copyright © 2017 Kosin University School of Medicine Proceedings

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Objectives
    The role of rheumatoid factor (RF) in vascular stiffness and cardiovascular risk in subjects without joint symptoms remains unclear. We investigated vascular stiffness in subjects without joint symptoms using pulse wave velocity (PWV), calculated Framingham risk scores (FRS), an estimator of cardiovascular risk, and analyzed whether vascular stiffness and FRS were affected by RF.
  • Methods
    Two hundred forty-two subjects were included in this population-based study. RF was quantified with turbid immunometry using a cut-off of RF > 15 IU/ml to denote RF positivity. Information was then obtained on joint symptoms. Brachial-ankle PWV (baPWV) was measured using an automated device.
  • Results
    Of the 242 subjects, 15 were RF-positive. RF-positive subjects without joint symptoms had a higher baPWV and FRS than RF-negative subjects without joint symptoms, but the difference did not reach statistical significance. However, when we stratified the subjects into two groups (group A – high RF: RF ≥ 40 IU/ml; group B – low RF: RF < 40 IU/ml), group A showed significantly higher baPWV (1640.7 ± 179.6 ㎝/s vs. 1405.7 ± 225.7 ㎝/s, P= 0.008) and FRS (25.7 ± 4.87 vs. 11.8 ± 9.6, P< 0.001). Multiple regression analysis was used to examine potential confounders, and RF exhibited significant but modest effects on baPWV (adjusted R-squared = 0.038, P= 0.030).
  • Conclusions
    In a sample of the general population without joint symptoms, higher levels of RF were associated with increased vascular stiffness, suggesting a pathophysiologic link between RF and endothelial dysfunction.
Fig. 1.
Study population flowchart.
kmj-32-25f1.jpg
Table 1.
Subjects’ characteristics
Men (n = 164) Women (n = 78) P
Age (years) 51.85±7.18 50.76±9.20 0.31
Smoking (n, %) 51 (31.1%) 3 (3.8%) < 0.001
Diabetes mellitus (n, %) 13 (7.9%) 3 (3.8%) 0.28
Hypertension (n, %) 24 (14.6%) 11 (14.1%) 0.99
SBP (mmHg) 126.7±15.07 124.8±14.61 0.35
DBP (mmHg) 80.3±11.89 76.1±10.56 0.008
Total cholesterol (mmol/l) 198.1±33.42 196.8±34.18 0.78
HDL (mmol/l) 49.2±11.58 61.6±17.52 < 0.001
LDL (mmol/l) 123.2±30.8 116.3±28.43 0.09
Triglyceride (mmol/l) 155.3±104.86 101.6±54.03 < 0.001
BMI (kg/㎡) 24.5±2.67 23.2±2.78 < 0.001
ABI 1.1±0.06 1.09±.062 0.25
BaPWV (㎝/s) 1424.4±225.21 1387.6±232.29 0.24
Uric acid 6.04±1.25 4.2±1.12 < 0.001
FRS 15.5±10.07 5.2±3.95 < 0.001
RF (IU/mL) 8.7±14.09 7.0±3.84 0.14

Data are presented as number (%) or mean SD unless otherwise indicated. P< 0.05 was considered statistically significant. SBP, Systolic blood pressure; DBP, Diastolic blood pressure; HDL, high density lipoprotein; LDL, low density lipoprotein; BMI, body mass index; ABI, ankle brachial index; baPWV, brachial ankle pulse wave velocity; FRS, Framingham risk score; RF, rheumatoid factor

Table 2.
Baseline characteristics of RF-negative and RF-positive subjects. RF-positive subjects without joint symptoms had higher baPWV and FRS than RF-negative subjects, but neither comparison reached statistical significance
RF-negative (n = 227) RF-positive (n = 15) P
Mean (SD) age (years) 53.40±7.20 51.38±7.94 0.123
Female sex (n, %) 74 (32.6%) 4 (26.7%) 0.780
Smoking (n, %) 2 (13.3%) 52 (22.9%) 0.532
Diabetes mellitus (n, %) 0 (0.0%) 16 (7.0%) 0.607
HBP (n, %) 3 (20.0%) 32 (14.1%) 0.461
Systolic blood pressure (mmHg) 124.73±14.94 126.20±14.95 0.560
Diastolic blood pressure (mmHg) 78.73±8.75 79.01±11.81 0.499
Total cholesterol (mmol/l) 187.93±21.11 198.37±34.21 0.144
HDL (mmol/l) 52.47±23.62 53.32±14.22 0.299
LDL (mmol/l) 121.60±24.20 120.94±30.62 0.843
Triglyceride (mmol/l) 137.20±57.93 138.11±96.93 0.379
BMI (㎏/㎡) 24.11±2.74 24.13±2.78 0.927
ABI 1.10±0.07 1.10±0.06 0.533
Mean baPWV (㎝/s) 1408.60±226.10 1472.60±251.03 0.312
Uric acid 5.50±1.42 5.47±1.48 0.742
Framingham 11.99±9.78 16.23±10.25 0.097

Data are presented as number (%) or mean SD unless otherwise indicated. P< 0.05 was considered statistically significant. SBP, Systolic blood pressure; DBP, Diastolic blood pressure; HDL, high density lipoprotein; LDL, low density lipoprotein; BMI, body mass index; ABI, ankle brachial index; baPWV, brachial ankle pulse wave velocity; FRS, Framingham risk score

Table 3.
Comparison between high (≥ 40 IU/mL) and low (< 40 IU/mL) RF group. Significantly higher baPWV and FRS values were noted in group A when compared with those of group B
Group A (n = 7) Group B (n = 235) P
Mean (SD) age (years) 58.00±3.00 51.31±7.91 0.003
Female sex (n, %) 0 (0.0%) 78 (33.2%) 0.100
Smoking (n, %) 1 (14.3%) 53 (22.6%) > 0.99
Diabetes mellitus (n, %) 0 (0.0%) 16 (6.8%) > 0.99
HBP (n, %) 1 (14.3%) 34 (14.5%) > 0.99
Systolic blood pressure (mmHg) 133.14±15.96 125.90±14.88 0.238
Diastolic blood pressure (mmHg) 83.29±9.48 78.86±11.68 0.466
Total cholesterol (mmol/l) 186.86±14.95 198.05±33.97 0.315
HDL (mmol/l) 45.86±7.71 53.49±15.02 0.204
LDL (mmol/l) 123.43±18.36 120.91±30.53 0.765
Triglyceride (mmol/l) 136.14±23.03 138.11±96.231 0.270
BMI (㎏/㎡) 23.87±1.52 24.13±2.80 0.822
ABI 1.13±0.09 1.10±0.06 0.622
Mean baPWV (㎝/s) 1640.71±179.64 1405.77±225.75 0.008
Uric acid 6.26±0.77 5.44±1.48 0.086
Framingham 25.77±4.87 11.85±9.67 < 0.001

Data are presented as number (%) or mean SD unless otherwise indicated. P< 0.05 was considered statistically significant. SBP, Systolic blood pressure; DBP, Diastolic blood pressure; HDL, high density lipoprotein; LDL, low density lipoprotein; BMI, body mass index; ABI, ankle brachial index; baPWV, brachial ankle pulse wave velocity; FRS, Framingham risk score.

Table 4.
Multiple regression analysis between baPWV and clinical parameters. Age, SBP, and RF were identified as significant contributors to increased baPWV in multiple regression analysis
Univariate analysis Multivariate analysis
Coefficient (β) 95% CI P R2 Coefficient (β) P
Age 11.897 8.555-15.238 < 0.001 0.170 8.367 < 0.001
SBP (mmHg) 9.516 8.000-11.031 < 0.001 0.389 7.720 < 0.001
DBP (mmHg) 8.066 5.797-10.335 < 0.001 0.170 1.771 0.122
Total cholesterol (mmol/L) 0.442 -0.417-1.302 0.312 0.004 -0.593 0.421
HDL (mmol/L) -1.061 -2.999-0.877 0.282 0.005 -0.859 0.338
LDL (mmol/L) 0.287 -0.670-1.245 0.555 0.001 1.106 0.148
Triglyceride (mmol/L) 0.262 -0.042-0.565 0.091 0.012 -0.096 0.518
BMI (㎏/㎡) 4.100 -6.322-14.522 0.775 0.002 -7.128 0.081
RF (IU/mL) 3.743 1.341-6.145 0.002 0.038 1.194 0.030
baPWV(R2 = 0.497, adjusted R2 = 0.477 in multivariate analysis)

Data are presented as number (%) or mean SD unless otherwise indicated. P< 0.05 was considered statistically significant. SBP, Systolic blood pressure; DBP, Diastolic blood pressure; HDL, high density lipoprotein; LDL, low density lipoprotein; BMI, body mass index; RF, rheumatoid factor.

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