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北京大学学报（医学版） ›› 2020, Vol. 52 ›› Issue (6): 1040-1047. doi: 10.19723/j.issn.1671-167X.2020.06.009

• 论著 • 上一篇    下一篇

老年发病类风湿关节炎的临床特征及其心血管疾病危险因素分析:一项大样本横断面临床研究

陈家丽,金月波,王一帆,张晓盈,李静,姚海红,何菁,李春()   

  1. 北京大学人民医院风湿免疫科,北京 100044
  • 收稿日期:2020-07-10 出版日期:2020-12-18 发布日期:2020-12-13
  • 通讯作者: 李春 E-mail:13811190098@163.com
  • 基金资助:
    国家自然科学基金(81701598);国家自然科学基金(81801618);北京市自然科学基金(7192211)

Clinical characteristics and risk factors of cardiovascular disease in patients with elderly-onset rheumatoid arthritis: A large cross-sectional clinical study

Jia-li CHEN,Yue-bo JIN,Yi-fan WANG,Xiao-ying ZHANG,Jing LI,Hai-hong YAO,Jing HE,Chun LI()   

  1. Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing 100044, China
  • Received:2020-07-10 Online:2020-12-18 Published:2020-12-13
  • Contact: Chun LI E-mail:13811190098@163.com
  • Supported by:
    National Natural Science Foundation of China(81701598);National Natural Science Foundation of China(81801618);Beijing Natural Science Foundation(7192211)

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摘要：

目的:了解我国老年发病类风湿关节炎(elderly-onset rheumatoid arthritis, EORA)患者的临床特点及其心血管疾病(cardiovascular disease, CVD)发生的危险因素。方法:收集2009年7月至2014年12月于北京大学人民医院就诊的1 116例类风湿关节炎(rheumatoid arthritis, RA)患者的临床资料及CVD(缺血性心脏病、脑及外周血管病)患病情况。根据发病年龄≥60岁和<60岁,分为EORA组(212例)和青壮年发病RA组(younger-onset RA, YORA, 904例),采用Student’s t检验、非参数U检验、 χ2检验比较两组间差异,并通过Logistic回归分析EORA合并CVD的危险因素。结果:EORA和YORA两组的疾病活动度差异无统计学意义。EORA组男性患者比例、肺间质病变比例、畸形关节数显著高于YORA组[(32.1% vs. 18.5%, χ2=19.11, P<0.001; 23.6% vs. 13.6%, χ2=16.50, P<0.001; 6 (2, 12) vs. 3 (2, 7), Z=-3.60, P<0.001)],而合并干燥综合征的比例低于YORA组(13.5% vs. 5.2%, χ2=11.29,P=0.001)。EORA组未用改善病情的抗风湿药(disease-modifying antirheumatic drugs, DMARDs)的比例高于YORA组(35.4% vs. 26.7%, χ2=6.43,P=0.011),羟氯喹(hydroxychloroquine, HCQ)、甲氨蝶呤(methotrexate, MTX)及柳氮磺吡啶(sulfasalazine, SSZ)的使用率显著低于YORA组。EORA组CVD发生率显著高于YORA组(27.8% vs. 11.6%, χ2=40.46, P<0.001),传统心血管危险因素中的吸烟、高血压及高脂血症比例也更高。多因素Logistic回归分析表明,高龄(OR=1.10,95%CI:1.00~1.20)、畸形关节数(OR=3.17,95%CI:1.04~9.68)、类风湿结节(OR=3.56,95%CI:1.03~12.23)、高血压(OR=2.37,95%CI:1.09~5.13)、高脂血症(OR=8.85,95%CI:2.50~31.27)是CVD的危险因素,使用HCQ(OR=0.22,95%CI:0.07~0.70)和MTX(OR=0.32,95%CI:0.14~0.73)是CVD的保护因素。结论:与YORA相比,EORA中男性及肺间质病变的患者更多,易出现关节畸形,可能与治疗欠规范有关。EORA易合并CVD,高龄、畸形关节数、类风湿结节、高血压、高脂血症是危险因素,而HCQ和MTX的使用是保护因素。

关键词: 类风湿关节炎, 老年人, 心血管疾病, 危险因素

Abstract:

Objective: To investigate the clinical characteristics of patients with elderly-onset rheumatoid arthritis (EORA), and the risk factors of EORA complicated with cardiovascular disease (CVD). Methods: A cross-sectional study was conducted in Peking University People’s Hospital from July 2009 to December 2014 and 1 116 patients were recruited. The patients’ characteristics and CVD, including ischemic heart disease, cerebral and peripheral vascular disease, were recorded. The patients were divided into EORA group (n=212) and younger-onset rheumatoid arthritis (YORA) group (n=904) according to the age of onset ≥60 years and <60 years. Then, the differences between the groups were analyzed by Student’s t test, Mann-Whitney U test or χ2test, and risk influencing CVD were analyzed using Logistic regression. Results: There was no significant difference in the disease activity between the EORA and YORA groups. The proportion of male, pulmonary interstitial disease (ILD), and numbers of deformity joint count (DJC) were significantly higher in the EORA group compared with the YORA group [32.1% vs. 18.5%, χ2=19.11, P<0.001; 23.6% vs. 13.6%, χ2=16.50, P<0.001; 6 (2, 12) vs. 3 (2, 7), Z=-3.60, P<0.001], while the prevalence of Sj?gren’s syndrome was lower than that of the YORA group (13.5% vs. 5.2%, χ2=11.29, P=0.001). Moreover, there were lower prevalences in the patients treated with disease-modifying antirheumatic drugs (DMARDs) in EORA group (35.4%) than in YORA group (26.7%) (χ2=6.43, P=0.011), especially in methotrexate (MTX), hydroxychloroquine (HCQ) and sulfasalazine (SSZ). In addition, the patients with EORA had a higher prevalence of CVD (27.8%) than the YORA group (11.6%, χ2=40.46, P<0.001), accompanied with higher prevalence of smoking, hypertension, and hyperlipidemia. Multivariate Logistic regression analysis showed that elder age (OR=1.10, 95%CI: 1.00-1.20), DJC (OR=3.17, 95%CI: 1.04-9.68), rheumatoid nodules (OR=3.56, 95%CI: 1.03-12.23), hypertension (OR=2.37, 95%CI: 1.09-5.13) and hyperlipidemia (OR=8.85, 95%CI: 2.50-31.27) were independent risk factors, while HCQ (OR=0.22, 95%CI: 0.07-0.70) and MTX (OR=0.32, 95%CI: 0.14-0.73) were protective factors of EORA complicated with CVD. Conclusion: Compared with YORA, patients with EORA have higher ratio of male, ILD and DJC, which may be attributed to inappropriate therapies. EORA is more likely to be complicated with CVD than YORA. Elder age, DJC, rheumatoid nodules, hypertension, and hyperlipidemia are independent risk factors, while HCQ and MTX are protective factors of EORA complicated with CVD.

Key words: Rheumatoid arthritis, Aged, Cardiovascular diseases, Risk factors

中图分类号: 

  • R593.22

表1

RA患者临床特征"

Items All patients (n=1 116) EORA (n=212) YORA (n=904) Z/χ2 P value
Male 235 (21.1) 68 (32.1) 167 (18.5) 19.11 <0.001
Age/years 57 (48, 66) 72 (68, 77) 53 (45, 59) -19.84 <0.001
Age of RA onset/years 47 (37, 57) 68 (63, 71) 43 (34, 51) -22.69 <0.001
Disease duration/years 6 (2, 14) 2 (1, 6) 7 (2, 15) -10.31 <0.001
SJCs 3 (1, 9) 4 (1, 10) 3 (1, 9) -1.00 0.319
TJCs 5 (2, 14) 7 (2, 18) 5 (2, 13) -1.41 0.159
DJCs 5 (2, 12) 6 (2, 12) 3 (2, 7) -3.60 <0.001
ESR/(mm/h) 41 (22, 69) 48 (25, 69) 46 (25, 76) -0.42 0.673
CRP/(mg/L) 11.4 (2.6, 39.0) 12.5 (2.3, 46.7) 10.8 (2.6, 38.2) -0.09 0.927
DAS28-ESR 4.53 (3.54, 5.60) 4.57 (3.70, 5.73) 4.53 (3.51, 5.70) -0.30 0.550
≤2.6 98 (8.8) 16 (9.4) 82 (9.1) 0.50 0.481
>2.6, ≤3.2 97 (8.7) 15 (7.1) 82 (9.1) 0.86 0.353
>3.2, ≤5.1 512 (45.9) 104 (47.2) 408 (45.1) 1.07 0.302
>5.1 409 (36.6) 77 (36.3) 332 (36.7) 0.01 0.912
Rheumatoid factor (positive) 799/929 (86.0) 145/170 (85.3) 654/759 (86.2) 0.09 0.767
Rheumatoid factor (positive) 799/929 (86.0) 145/170 (85.3) 654/759 (86.2) 0.09 0.767
Anti-CCP antibody (positive) 506/620 (81.6) 86/107 (80.4) 420/513 (81.9) 0.13 0.716
Extra-articular manifestations
Interstitial lung disease 164 (14.7) 50 (23.6) 114 (12.6) 16.50 <0.001
Pleural effusion 13 (1.2) 3 (1.4) 10 (1.1) 0.14 0.721
Pericardial effusion 2 (0.2) 1 (0.5) 1 (0.1) 1.25 0.344
Rheumatoid nodules 69 (6.2) 13 (6.1) 56 (6.2) 0.00 0.973
Cutaneous vasculitis 8 (0.7) 1 (0.5) 7 (0.8) 0.22 >0.999
Anemia 201 (18.0) 34 (16.0) 167 (18.5) 0.69 0.406
Peri-neuropathy 6 (0.5) 1 (0.5) 5 (0.6) 0.02 >0.999
Sj?gren’s syndrome 133 (11.9) 11 (5.2) 122 (13.5) 11.29 0.001
Medications
Non-DMARDs 316 (28.3) 75 (35.4) 241 (26.7) 6.43 0.011
Methotrexate 306 (27.4) 45 (21.2) 261 (28.9) 5.04 0.025
Hydroxychloroquine 349 (31.3) 39 (18.4) 310 (34.3) 20.19 <0.001
Leflunomide 433 (38.8) 86 (40.6) 347 (38.4) 0.34 0.560
Sulfasalazine 341 (30.6) 49 (23.1) 292 (32.3) 6.83 0.009
Prednisone 252 (22.6) 50 (23.6) 202 (22.3) 0.15 0.698
Celecoxib 28 (2.5) 9 (4.2) 19 (2.1) 3.23 0.072
Biological agents 128 (11.5) 20 (9.4) 108 (11.9) 1.07 0.301

表2

EORA和YORA患者CVD及传统危险因素患病率"

Items All patients (n=1 116) EORA (n=212) YORA (n=904) Z/χ2 P value
CVD 164 (14.7) 59 (27.8) 105 (11.6) 40.46 <0.001
Coronary heart disease 107 (9.6) 38 (17.9) 69 (7.6) 20.21 <0.001
Cerebral arterial disease 76 (6.8) 27 (12.7) 49 (5.4) 13.90 <0.001
Peripheral arterial disease 87 (7.8) 35 (16.5) 52 (5.8) 27.65 <0.001
BMI/(kg/m2) 22.8 (20.3, 25.3) 22.6 (20.2, 24.7) 22.9 (20.4, 25.5) -0.77 0.440
BMI≥24 365/972 (37.6) 69/180 (38.3) 296/792 (37.4) 0.06 0.810
Smoking 180 (16.1) 50 (23.6) 130 (14.4) 10.75 <0.001
Hypertension 294 (26.3) 95 (44.8) 199 (22.0) 45.86 <0.001
Diabetes mellitus 136 (12.2) 47 (22.2) 89 (9.8) 24.31 <0.001
Hyperlipidemia 72 (6.5) 23 (10.8) 49 (5.4) 8.03 0.005

表3

EORA合并CVD与不合并CVD临床特征的差异"

Items CVD (n=59) Without CVD (n=153) Z/χ2 P value
Male 22 (37.3) 46 (30.1) 1.02 0.313
Age/years 74 (70, 78) 70 (67, 75) -3.12 0.002
Disease duration/years 4 (1, 8) 2 (1, 5) -1.83 0.068
SJCs 3 (1, 8) 4 (1, 10) -0.50 0.620
TJCs 6 (2, 15) 6 (2, 17) -0.77 0.444
DJCs 28 (47.5) 51 (33.3) 3.63 0.057
ESR/(mm/h) 47 (30, 65) 43 (23, 71) -0.36 0.716
CRP/(mg/L) 10.4 (2.8, 37.7) 14.0 (1.8, 46.7) -0.77 0.442
DAS28-ESR 4.6 (3.7, 5.7) 4.5 (3.7, 5.8) -0.47 0.636
≤2.6 6 (8.5) 10 (6.5) 0.81 0.369
>2.6, ≤3.2 4 (6.8) 11 (7.2) 0.01 >0.999
>3.2, ≤5.1 29 (49.2) 75 (49.0) 0.00 0.986
>5.1 20 (33.9) 57 (37.3) 0.21 0.649
Rheumatoid factor (positive) 14/49 (28.6) 11/121 (9.1) 10.55 0.001
Anti-CCP antibody (positive) 10/30 (33.3) 13/79 (16.5) 3.72 0.054
Extra-articular manifestations
Interstitial lung disease 16 (27.1) 34 (22.2) 0.57 0.452
Pleural effusion 2 (3.4) 1 (0.6) 2.29 0.188
Pericardial effusion 1 (1.7) 0 (0) 2.606 0.278
Rheumatoid nodules 7 (11.9) 6 (3.9) 4.67 0.050
Cutaneous vasculitis 0 (0) 1 (0.6) 0.387 >0.999
Anemia 10 (16.9) 24 (15.7) 0.050 0.822
Peri-neuropathy 0 (0) 1 (0.6) 0.387 >0.999
Sj?gren’s syndrome 4 (6.8) 7 (4.6) 0.421 0.503
Medications
Non-DMARDs 16 (27.1) 59 (38.6) 2.44 0.118
Methotrexate 9 (15.3) 54 (35.3) 10.09 0.004
Hydroxychloroquine 4 (6.8) 35 (22.9) 7.35 0.007
Leflunomide 25 (42.4) 61 (39.9) 0.11 0.739
Sulfasalazine 9 (15.3) 40 (26.1) 2.84 0.092
Prednisone 18 (3.1) 32 (20.9) 2.17 0.140
Celecoxib 2 (3.3) 7 (4.6) 0.15 0.701
Biological agents 3 (5.1) 17 (11.1) 1.81 0.179

表4

EORA合并CVD与不合并CVD在传统危险因素方面的差异"

Items CVD (n=59) Without CVD (n=153) Z/χ2 P value
BMI (kg/m2) 22.7 (19.9, 25.3) 22.6 (20.7, 24.6) -0.11 0.916
BMI<24 34/53 (64.2) 77/127 (60.6) 0.196 0.658
24≤BMI≤28 18/53 (34.0) 44/127 (34.6) 0.008 0.930
BMI>28 1/53 (1.9) 6/127 (4.7) 0.806 0.675
Smoking 19 (32.2) 31 (20.3) 3.37 0.066
Hypertension 38 (64.4) 57 (37.3) 12.69 <0.001
Diabetes mellitus 18 (30.5) 29 (19.0) 3.29 0.070
Hyperlipidemia 18 (30.5) 5 (3.3) 31.93 <0.001

表5

EORA合并CVD危险因素"

Risk factors OR (95%CI) P value
Male 0.73 (0.27, 1.97) 0.536
Age 1.10 (1.00, 1.20) 0.040
Disease duration 0.99 (0.87, 1.12) 0.819
SJCs 0.91 (0.24, 3.53) 0.894
TJCs 0.90 (0.20, 3.99) 0.889
DJCs 3.17 (1.04, 9.68) 0.043
ESR 1.92 (0.50, 7.39) 0.344
CRP 0.62 (0.21, 1.84) 0.386
Anti-CCP antibody 0.48 (0.14, 1.65) 0.243
DAS28-ESR
>2.6, ≤3.2 0.11 (0.01, 1.50) 0.098
>3.2, ≤5.1 0.59 (0.07, 4.92) 0.629
>5.1 0.67 (0.23, 1.98) 0.473
ILD 0.77 (0.38, 1.57) 0.464
Anemia 1.19 (0.48, 2.93) 0.712
Rheumatoid nodules 3.56 (1.03, 12.23) 0.044
Hydroxychloroquine 0.22 (0.07, 0.70) 0.011
Methotrexate 0.32 (0.14, 0.73) 0.007
Sulfasalazine 0.69 (0.28, 1.75) 0.440
Leflunomide 1.03 (0.46, 2.31) 0.949
Corticosteroid 1.09 (0.46, 2.59) 0.854
Celecoxib 0.66 (0.12, 3.55) 0.628
Biological 0.39 (0.10, 1.58) 0.188
24≤BMI<28 3.41 (0.27, 42.55) 0.341
BMI≥28 3.42 (0.26, 44.26) 0.347
Smoking 1.66 (0.58, 4.80) 0.347
Hypertension 2.37 (1.09, 5.13) 0.029
Diabetes 0.94 (0.37, 2.40) 0.900
Hyperlipemia 8.85 (2.50, 31.27) 0.001
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