背景:临床前类风湿性关节炎(Pre-RA)被定义为临床RA发展之前的早期阶段。虽然恶病质是RA的一种众所周知的潜在可改变的并发症,不知道这种关联是否也存在于RA前阶段。为了调查这样的问题,我们的目的是比较RA前期参与者与配对对照的肌肉组成和肥胖的纵向变化.
方法:在这项观察性队列研究中,骨关节炎倡议(OAI)参与者被分为RA前期和倾向评分(PS)匹配的对照组.RA前期的回顾性定义为从基线到第2年没有RA,在随访的第3-8年之间进展为医生诊断的临床RA。使用经过验证的深度学习算法,我们在基线和队列第2年随访时测量了大腿肌肉和肥胖的MRI生物标志物.结果是前RA组和对照组在大腿肌肉组成[横截面积(CSA)和肌内脂肪组织(Intra-MAT)]和肥胖[肌间脂肪组织(Inter-MAT)和皮下脂肪组织(SAT)]的2年变化率方面的差异。使用线性混合效应回归模型进行比较。
结果:在对混杂变量进行1:3PS匹配后(人口统计,危险因素,合并症,和膝关节骨关节炎状态),包括322名参与者的408条大腿(102条RA前和306条对照)(年龄平均值±SD:61.7±8.9岁;女性/男性:1.8)。在两年的时间里,RA前期与大腿总肌肉CSA下降幅度较大相关[估计,95%置信区间(CI):-180.13mm2/2年,-252.80至-107.47,P值<0.001]。大腿肌肉组成的进一步检查表明,在股四头肌中,Pre-RA的存在与超过2年的肌肉CSA的较大减少有关。屈肌,和缝匠肌群(P值<0.05)。总脂肪组织变化的比较显示,Pre-RA和对照参与者之间没有差异(估计,95%CI:48.48mm2/2年,-213.51至310.47,P值=0.691)。然而,在大腿肥胖的详细分析中,RA前的存在与MAT间的较大增加相关(估计,95%CI:150.55mm2/2年,95.58至205.51,P值<0.001)。
结论:临床前类风湿性关节炎与肌肉横截面积的减少和肌肉间脂肪组织的增加有关,类似于临床类风湿关节炎的类风湿性关节炎恶病质。这些发现表明在类风湿性关节炎的临床前期存在恶病质。鉴于恶病质,这会加剧健康结果,可能是可修改的,这项研究强调了在临床前阶段早期识别患者的重要性.
BACKGROUND: Preclinical rheumatoid arthritis (Pre-RA) is defined as the early stage before the development of clinical RA. While cachexia is a well-known and potentially modifiable complication of RA, it is not known if such an association exists also in the Pre-RA stage. To investigate such issue, we aimed to compare the longitudinal alterations in the muscle composition and adiposity of participants with Pre-RA with the matched controls.
METHODS: In this observational cohort study, the Osteoarthritis Initiative (OAI) participants were categorized into Pre-RA and propensity score (PS)-matched control groups. Pre-RA was retrospectively defined as the absence of RA from baseline to year-2, with progression to physician-diagnosed clinical RA between years 3-8 of the follow-up period. Using a validated deep learning algorithm, we measured MRI biomarkers of thigh muscles and adiposity at baseline and year-2 follow-ups of the cohort. The outcomes were the differences between Pre-RA and control groups in the 2-year rate of change for thigh muscle composition [cross-sectional area (CSA) and intramuscular adipose tissue (Intra-MAT)] and adiposity [intermuscular adipose tissue (Inter-MAT) and subcutaneous adipose tissue (SAT)]. Linear mixed-effect regression models were used for comparison.
RESULTS: After 1:3 PS-matching of the groups for confounding variables (demographics, risk factors, co-morbidities, and knee osteoarthritis status), 408 thighs (102 Pre-RA and 306 control) of 322 participants were included (age mean ± SD: 61.7 ± 8.9 years; female/male: 1.8). Over a 2-year period, Pre-RA was associated with a larger decrease in total thigh muscle CSA [estimate, 95% confidence interval (CI): -180.13 mm2/2-year, -252.80 to -107.47, P-value < 0.001]. Further examination of thigh muscle composition showed that the association of the presence of Pre-RA with a larger decrease in muscle CSA over 2 years was noticeable in the quadriceps, flexors, and sartorius muscle groups (P-values < 0.05). Comparison of changes in total adipose tissue showed no difference between Pre-RA and control participants (estimate, 95% CI: 48.48 mm2/2-year, -213.51 to 310.47, P-value = 0.691). However, in the detailed analysis of thigh adiposity, Pre-RA presence was associated with a larger increase in Inter-MAT (estimate, 95% CI: 150.55 mm2/2-year, 95.58 to 205.51, P-value < 0.001).
CONCLUSIONS: Preclinical rheumatoid arthritis is associated with a decrease in muscle cross-sectional area and an increase in intermuscular adipose tissue, similar to rheumatoid cachexia in clinical rheumatoid arthritis. These findings suggest the presence of cachexia in the preclinical phase of rheumatoid arthritis. Given that cachexia, which can exacerbate health outcomes, is potentially modifiable, this study emphasizes the importance of early identification of patients in their preclinical phase.