Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; NIHR Manchester Musculoskeletal Biomedical Research Unit, University of Manchester, Manchester, UK.
Biomedical Imaging Institute, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
Lancet. 2015 Feb 26;385 Suppl 1:S91. doi: 10.1016/S0140-6736(15)60406-8.
Rheumatoid arthritis is associated with a 50% increased risk in cardiovascular mortality. Inflammation is thought to accelerate atherosclerosis and might also lead to an inflammatory rupture-prone plaque phenotype. We tested the hypothesis that patients with active rheumatoid arthritis also have carotid plaque inflammation and that plaque inflammation correlates with clinical and serological markers of inflammation.
Patients with active rheumatoid arthritis, defined as the Disease Activity Score in 28 joints (DAS28) score of more than 3·2, were recruited to a single centre study in the UK. Patients with carotid plaque on ultrasound underwent carotid MRI followed by (18)F-fluorodeoxyglucose ((18)F-FDG) PET-CT. Scans were co-registered and analysed by a physicist, masked to clinical information. The maximum standardised uptake values (SUV(max)) were measured in the plaque area. The association of SUV with DAS28, C-reactive protein, and CD4+CD28- T-cell frequency was tested with non-parametric statistics. Ethics approval and informed consent were obtained.
Scans were done in 13 patients, nine of whom were women. Median age was 60 years (IQR 57-65), disease duration was 11 years (6-25), and DAS28 score was 4·52 (4·32-5·13). None had a history or symptoms of clinical cardiovascular disease or took statins. All plaques caused less than 70% stenosis, and tracer uptake in plaque was seen on PET in all 13 patients. Median SUV(max) was 2·18 (IQR 2·00-2·65), and all cases had an SUV(max) greater than 1·6 (the threshold for defining carotid plaque inflammation). There was a significant association with SUV(max) and C-reactive protein (r=0·58, p=0·04) and quartiles of CD4+CD28- T-cell frequency (p=0·045), but not with low-density lipoprotein concentrations (r=-0·49, p=0·09) or DAS28 score (r=0·38, p=0·20). No association was found with age (r=0·13, p=0·69) or sex (p=0·64).
In this small pilot study, plaque inflammation was seen in all patients and correlated with C-reactive protein. Whether this finding represents simultaneous joint and plaque inflammation, which might improve on treatment of joint disease, remains to be determined. CD4+CD28- T-cells are known to predict cardiovascular events in patients with angina. Their association with plaque inflammation in this study suggests a possible role in cardiovascular risk prediction in rheumatoid arthritis. Larger studies are warranted to investigate these findings further.
North West England MRC Clinical Pharmacology and Therapeutics Clinical Research Fellowship, National Institute for Health Research, AstraZeneca-University of Manchester Strategic Alliance Fund.
类风湿关节炎与心血管死亡率增加 50%相关。炎症被认为会加速动脉粥样硬化，并且可能导致易发生炎症破裂的斑块表型。我们检验了这样一种假设，即患有活动期类风湿关节炎的患者颈动脉斑块也存在炎症，且斑块炎症与炎症的临床和血清学标志物相关。
在英国的一个单一中心研究中，招募了符合以下条件的活动期类风湿关节炎患者：28 关节疾病活动度评分（DAS28）超过 3.2。对颈动脉超声显示斑块的患者进行颈动脉 MRI 检查，随后进行（18）F-氟脱氧葡萄糖（（18）F-FDG）PET-CT。扫描由物理学家进行配准和分析，对临床信息进行盲法处理。在斑块区域测量最大标准化摄取值（SUV(max))。使用非参数统计学方法检验 SUV 与 DAS28、C 反应蛋白和 CD4+CD28-T 细胞频率的相关性。本研究获得了伦理批准并获得了知情同意。
对 13 名患者进行了扫描，其中 9 名为女性。中位年龄为 60 岁（IQR 57-65），疾病持续时间为 11 年（6-25），DAS28 评分为 4.52（4.32-5.13）。患者均无心血管疾病的临床病史或症状，也未服用他汀类药物。所有斑块造成的狭窄程度均低于 70%，并且在 13 名患者中均在 PET 上观察到斑块摄取示踪剂。SUV(max)的中位数为 2.18（IQR 2.00-2.65），所有患者的 SUV(max)均大于 1.6（定义颈动脉斑块炎症的阈值）。SUV(max)与 C 反应蛋白呈显著相关（r=0.58，p=0.04），与 CD4+CD28-T 细胞频率的四分位数也呈显著相关（p=0.045），但与低密度脂蛋白浓度（r=-0.49，p=0.09）或 DAS28 评分（r=0.38，p=0.20）无关。年龄（r=0.13，p=0.69）和性别（p=0.64）与 SUV(max)均无相关性。
在这项小型试点研究中，所有患者均存在斑块炎症，且与 C 反应蛋白相关。这种发现是否代表关节和斑块同时存在炎症，而这种炎症可能会改善关节疾病的治疗效果，还有待确定。已知 CD4+CD28-T 细胞可预测心绞痛患者的心血管事件。在本研究中，它们与斑块炎症相关，提示其可能在类风湿关节炎的心血管风险预测中发挥作用。需要进行更大规模的研究来进一步探讨这些发现。
英国西北英格兰 MRC 临床药理学和治疗学临床研究奖学金、英国国家卫生研究院、阿斯利康-曼彻斯特大学战略联盟基金。
