Philadelphia VA Medical Center.
Perelman School of Medicine.
Rheumatology (Oxford). 2022 Nov 28;61(12):4924-4934. doi: 10.1093/rheumatology/keac191.
This study assessed whether circulating levels of adiponectin and leptin are associated with higher mortality in patients with RA.
Participants were adults from the Veterans Affairs RA Registry. Adipokines and inflammatory cytokines were measured as part of a multi-analyte panel on banked serum at enrolment. Dates and causes of death were derived from the Corporate Data Warehouse and the National Death Index. Covariates were derived from medical record, biorepository and registry databases. Multivariable Cox proportional hazard models evaluated associations between biomarkers and all-cause and cause-specific mortality.
A total of 2583 participants were included. Higher adiponectin levels were associated with older age, male sex, white race, lower BMI, autoantibody seropositivity, radiographic damage, longer disease duration, prednisone use and osteoporosis. Higher adiponectin concentrations were also associated with higher levels of inflammatory cytokines but not higher disease activity at enrolment. Leptin was primarily associated with greater BMI and comorbidity. The highest quartile of adiponectin (vs lowest quartile) was associated with higher all-cause mortality [hazard ratio (HR): 1.46 (95% CI: 1.11, 1.93), P = 0.009] and higher cardiovascular mortality [HR: 1.85 (95% CI: 1.24, 2.75), P = 0.003], after accounting for covariates. Higher leptin levels were also associated with greater all-cause and cancer mortality.
Elevations in adipokines are associated with age, BMI, comorbidity and severe disease features in RA and independently predict early death. Associations between adiponectin and inflammatory cytokines support the hypothesis that chronic subclinical inflammation promotes metabolic changes that drive elevations in adipokines and yield adverse health outcomes.
本研究旨在评估循环脂联素和瘦素水平与 RA 患者更高死亡率之间的关系。
参与者来自退伍军人事务部 RA 登记处的成年人。脂联素和炎症细胞因子作为纳入时银行储存血清多分析物检测的一部分进行测量。死亡日期和原因来自公司数据仓库和国家死亡索引。协变量来自病历、生物库和登记数据库。多变量 Cox 比例风险模型评估了生物标志物与全因和特定原因死亡率之间的关联。
共纳入 2583 名参与者。较高的脂联素水平与年龄较大、男性、白种人、较低的 BMI、自身抗体阳性、放射学损伤、疾病持续时间较长、使用泼尼松和骨质疏松症有关。较高的脂联素浓度也与更高水平的炎症细胞因子相关，但与纳入时的疾病活动度无关。瘦素主要与更大的 BMI 和合并症相关。脂联素最高四分位数（与最低四分位数相比）与全因死亡率较高相关[风险比 (HR)：1.46（95% CI：1.11，1.93），P=0.009]和心血管死亡率较高[HR：1.85（95% CI：1.24，2.75），P=0.003]，在考虑了协变量后。较高的瘦素水平也与全因和癌症死亡率增加相关。
脂联素水平升高与 RA 中的年龄、BMI、合并症和严重疾病特征相关，并独立预测早期死亡。脂联素与炎症细胞因子之间的关联支持慢性亚临床炎症促进代谢变化的假说，这种变化导致脂联素水平升高并产生不良健康后果。
