Løgstrup Brian B, Deibjerg Lone K, Hedemann-Andersen Agnete, Ellingsen Torkell
Diagnostic Centre Region Hospital Silkeborg, Denmark ; Department of Cardiology, Aarhus University Hospital Skejby, Denmark.
Diagnostic Centre Region Hospital Silkeborg, Denmark.
Am J Cardiovasc Dis. 2014 Jun 28;4(2):79-86. eCollection 2014.
The role of inflammation and anti-cyclic citrullinated peptide antibodies (anti-CCP) in the pathogenesis of cardiovascular disease in early rheumatoid arthritis (RA) remains unclear. Previous studies have suggested that both disease activity and disease duration are associated with atherosclerosis and a higher mortality rate caused primarily by coronary artery disease.
We investigated how disease activity, anti-CCP status and coronary calcium score in treatment-naive early RA impacts left ventricular (LV) systolic function.
Fifty-tree patients (30 women) with mean age 58.3±1.3 years and steroid- and disease-modifying antirheumatic drug (DMARD)-naive early RA were included. Disease activity was scored by the use of the Danish national DANBIO registry (number of swollen joints (NSJ (28)), number of tender joints (NTJ (28)), C-reactive protein (CRP) and Health Assessment Questionnaire (HAQ)). Pain, fatigue, patient and physician global assessment and a composite disease activity score (DAS28-CRP) were assessed by visual analog scales (VAS) 0-100. IgM rheumafactor (IgM-RF) and anti-CCP titers were evaluated by standardized techniques. Coronary calcium score was estimated by computed tomography by calculating the Agaston score. One experienced senior rheumatologist and one experienced cardiologist performed all the clinical assessments as well as all the transthoracic echocardiography (TTE) and coronary CT analysis.
Disease activity scores before treatment at baseline were: NSJ (28) 7.1±2.7, NTJ (28) 8.5±3.5, CRP 11.7±12.9 mmol/l, HAQ 0.71±0.6, pain VAS 51.1±23.7, fatigue VAS 49.3±24.9, physician global assessment 54.2±15.0 and DAS28-CRP 4.8±0.7. Twenty-three (43%) patients were IgM-RF positive and 33 (62%) were anti-CCP positive. We found LV systolic function by conventional ejection fraction (EF) to be 54.1±9.2% and to be non-significant correlated to disease activity (CRP: r=0.07, p=0.64; baseline NSJ: r=-0.13, p=0.33; NTJ: r=-0.08, p=0.58; HAQ: r=0.23, p=0.1; pain VAS: r=-0.05, p=0.74; fatigue VAS: r=0.03, p=0,83; physician global assessment: r=-0.09, p=0.54 and DAS28: r=-0.03, p=0.84). However, using a more sensitive measurement of the LV function by global longitudinal systolic strain (GLS), we found a significant correlation: HAQ (r=0.29; p=0.037), patient global assessment by VAS (r=0.35; p=0.011), patient fatigue assessment by VAS (r=0.3; p=0.03) and DAS28-CRP (r=0.28; p=0.043); all corrected for relevant confounders (age, gender, pulse and blood pressure). Furthermore, anti-CCP was highly significantly correlated with GLS (r=-0.44; p=0.001) in univariate analysis. In multivariate analysis, it still remained significantly correlated (p=0.018), after correction for age, gender, pulse, and blood pressure. Using strain analysis of LV function, we found a significant difference in GLS in patients with high values of anti-CCP (titers ≥340) compared to patients with anti-CCP (titers <340); (-19.9±2.1% vs. -16.4±2.8%; p=0.0001). For patients with high IgM-RF, results were non-significant.
We observed a significant correlation between increased disease activity and cardiac function in treatment-naive early RA.
炎症和抗环瓜氨酸肽抗体(抗CCP)在早期类风湿关节炎(RA)心血管疾病发病机制中的作用尚不清楚。先前的研究表明,疾病活动度和病程均与动脉粥样硬化以及主要由冠状动脉疾病导致的较高死亡率相关。
我们研究了初治早期类风湿关节炎患者的疾病活动度、抗CCP状态和冠状动脉钙化评分如何影响左心室(LV)收缩功能。
纳入53例(30例女性)平均年龄为58.3±1.3岁、未使用过类固醇和改善病情抗风湿药物(DMARD)的早期类风湿关节炎患者。采用丹麦国家DANBIO登记系统对疾病活动度进行评分(肿胀关节数(NSJ(28))、压痛关节数(NTJ(28))、C反应蛋白(CRP)和健康评估问卷(HAQ))。通过0-100视觉模拟量表(VAS)评估疼痛、疲劳、患者和医生整体评估以及综合疾病活动评分(DAS28-CRP)。采用标准化技术评估IgM类风湿因子(IgM-RF)和抗CCP滴度。通过计算机断层扫描计算阿加斯顿评分来估计冠状动脉钙化评分。由一位经验丰富的资深风湿病学家和一位经验丰富的心脏病学家进行所有临床评估以及所有经胸超声心动图(TTE)和冠状动脉CT分析。
基线治疗前的疾病活动度评分如下:NSJ(28)7.1±2.7,NTJ(28)8.5±3.5,CRP 11.7±12.9 mmol/l,HAQ 0.71±0.6,疼痛VAS 51.1±23.7,疲劳VAS 49.3±24.9,医生整体评估54.2±15.0,DAS28-CRP 4.8±0.7。23例(43%)患者IgM-RF阳性,33例(62%)患者抗CCP阳性。我们发现,通过传统射血分数(EF)测得的左心室收缩功能为54.1±9.2%,与疾病活动度无显著相关性(CRP:r=0.07,p=0.64;基线NSJ:r=-0.13,p=0.33;NTJ:r=-0.08,p=0.58;HAQ:r=0.23,p=0.1;疼痛VAS:r=-0.05,p=0.74;疲劳VAS:r=0.03,p=0.83;医生整体评估:r=-0.09,p=0.54;DAS28:r=-0.03,p=0.84)。然而,使用更敏感的整体纵向收缩应变(GLS)测量左心室功能时,我们发现存在显著相关性:HAQ(r=0.29;p=0.037)、患者VAS整体评估(r=0.35;p=0.011)、患者VAS疲劳评估(r=0.3;p=0.03)和DAS28-CRP(r=0.28;p=0.043);所有均校正了相关混杂因素(年龄、性别、脉搏和血压)。此外,在单因素分析中抗CCP与GLS高度显著相关(r=-0.44;p=0.001)。在多因素分析中,校正年龄、性别、脉搏和血压后,仍保持显著相关性(p=0.018)。使用左心室功能应变分析,我们发现抗CCP值高(滴度≥340)的患者与抗CCP(滴度<340)的患者相比,GLS存在显著差异;(-19.9±2.1%对-16.4±2.8%;p=0.0001)。对于IgM-RF高的患者,结果无统计学意义。
我们观察到初治早期类风湿关节炎患者疾病活动度增加与心脏功能之间存在显著相关性。