Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.
Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.
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DOI：
10.1053/j.ajkd.2015.01.021
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发表时间：
2015-08
期刊：
影响因子：
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通讯作者：
CRIC Study Investigators
中科院分区：
文献类型：
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作者：
Shah R;Matthews GJ;Shah RY;McLaughlin C;Chen J;Wolman M;Master SR;Chai B;Xie D;Rader DJ;Raj DS;Mehta NN;Budoff M;Fischer MJ;Go AS;Townsend RR;He J;Kusek JW;Feldman HI;Foulkes AS;Reilly MP;CRIC Study Investigators
心脏代谢疾病是慢性肾病（CKD）患者发病和死亡的主要原因。Fractalkine（CX 3CL 1）是动脉粥样硬化和代谢性疾病的潜在介质。缺乏关于CX 3CL 1与CVD事件风险和代谢特征关系的研究，特别是在CKD的高风险环境中。横向和纵向观察分析。来自参与慢性肾功能不全队列（CRIC）研究的7家美国研究中心的成人CKD患者。基线时血浆CX 3CL 1水平的四分位数。根据基于肌酐和胱抑素C的方程估计的基线肾小球滤过率（eGFR）、现患和偶发CVD、糖尿病、代谢综合征及其标准、胰岛素抵抗的稳态模型评估、血红蛋白A1 C、心肌梗死、全因死亡率和心肌梗死/全因死亡率的复合结局。在3687例受试者中，基线CX 3CL 1水平与几种CVD风险因素和代谢特征、较低eGFR和较高水平的炎性细胞因子以及普遍CVD呈正相关（OR，1.09; 95%CI，1.01-1.19; p=0.03）。在调整后的模型中，较高的CX 3CL 1也与糖尿病患病率相关（OR，1.26; 95%CI，1.16-1.38; p<0.001）。在平均6年的随访中，有352例死亡，176例心肌梗死，484例复合结局。在完全校正模型中，CX 3CL 1升高1-SD增加全因死亡率（1.11; 95% CI，1.00-1.22; p=0.02）和复合结局（1.09; 95% CI，1.00-1.19; p=0.04）的风险。研究设计不允许评价随时间的变化、与表型进展的相关性或确定效应的因果关系。在CKD队列中，循环CX 3CL 1可能导致动脉粥样硬化CVD和糖尿病。需要进一步的研究来建立CX 3CL 1影响动脉粥样硬化和糖尿病发病机制的机制。
Cardiometabolic disease is a major cause of morbidity and mortality in persons with chronic kidney disease (CKD). Fractalkine (CX3CL1) is a potential mediator of both atherosclerosis and metabolic disease. Studies on the relationship of CX3CL1 with risk of CVD events and metabolic traits are lacking, particularly in the high-risk setting of CKD. Cross-sectional and longitudinal observational analysis. Adults with CKD from 7 US sites participating in the Chronic Renal Insufficiency Cohort (CRIC) Study. Quartiles of plasma CX3CL1 levels at baseline. Baseline estimated glomerular filtration rate (eGFR) from a creatinine- and cystatin C–based equation, prevalent and incident CVD, diabetes, metabolic syndrome and its criteria, homeostatic model assessment of insulin resistance, hemoglobin A1C, myocardial infarction, all-cause mortality, and the composite outcome of myocardial infarction/all-cause mortality. Among 3687 participants, baseline CX3CL1 levels were positively associated with several CVD risk factors and metabolic traits, lower eGFR, and higher levels of inflammatory cytokines as well as prevalent CVD (OR, 1.09; 95% CI, 1.01–1.19; p=0.03). Higher CX3CL1 was also associated with prevalent diabetes (OR, 1.26; 95% CI, 1.16–1.38; p<0.001) in adjusted models. During a mean follow up of 6 years, there were 352 deaths, 176 myocardial infarctions, and 484 with composite outcomes. In fully-adjusted models, 1-SD higher CX3CL1 increased the hazard for all-cause mortality (1.11; 95% CI, 1.00–1.22; p=0.02) and the composite outcome (1.09; 95% CI, 1.00–1.19; p=0.04). Study design did not allow evaluation of changes over time, correlation with progression of phenotypes, or determination of causality of effect. Circulating CX3CL1 may contribute to both atherosclerotic CVD and diabetes in a CKD cohort. Further studies are required to establish mechanisms through which CX3CL1 affects pathogenesis of atherosclerosis and diabetes.