TY - JOUR
T1 - Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes
T2 - Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study
AU - Shah, Rachana
AU - Matthews, Gregory J.
AU - Shah, Rhia Y.
AU - McLaughlin, Catherine
AU - Chen, Jing
AU - Wolman, Melanie
AU - Master, Stephen R.
AU - Chai, Boyang
AU - Xie, Dawei
AU - Rader, Daniel J.
AU - Raj, Dominic S.
AU - Mehta, Nehal N.
AU - Budoff, Matthew
AU - Fischer, Michael J.
AU - Go, Alan S.
AU - Townsend, Raymond R.
AU - He, Jiang
AU - Kusek, John W.
AU - Feldman, Harold I.
AU - Foulkes, Andrea S.
AU - Reilly, Muredach P.
AU - Appel, Lawrence J.
AU - Lash, James P.
AU - Ojo, Akinlolu
AU - Rahman, Mahboob
N1 - Publisher Copyright:
© 2015 National Kidney Foundation, Inc.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - Background 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 of the relationship of CX3CL1 with risk of cardiovascular disease (CVD) events and metabolic traits are lacking, particularly in the high-risk setting of CKD. Study Design Cross-sectional and longitudinal observational analysis. Setting & Participants Adults with CKD from 7 US sites participating in the Chronic Renal Insufficiency Cohort (CRIC) Study. Predictor Quartiles of plasma CX3CL1 levels at baseline. Outcomes Baseline estimated glomerular filtration rate 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 level, myocardial infarction, all-cause mortality, and the composite outcome of myocardial infarction/all-cause mortality. Results Among 3,687 participants, baseline CX3CL1 levels were associated positively with several CVD risk factors and metabolic traits, lower estimated glomerular filtration rate, 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 level also was 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 composite outcomes. In fully adjusted models, 1-SD higher CX3CL1 level 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). Limitations Study design did not allow evaluation of changes over time, correlation with progression of phenotypes, or determination of causality of effect. Conclusions Circulating CX3CL1 level may contribute to both atherosclerotic CVD and diabetes in a CKD cohort. Further studies are required to establish mechanisms through which CX3CL1 affects the pathogenesis of atherosclerosis and diabetes.
AB - Background 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 of the relationship of CX3CL1 with risk of cardiovascular disease (CVD) events and metabolic traits are lacking, particularly in the high-risk setting of CKD. Study Design Cross-sectional and longitudinal observational analysis. Setting & Participants Adults with CKD from 7 US sites participating in the Chronic Renal Insufficiency Cohort (CRIC) Study. Predictor Quartiles of plasma CX3CL1 levels at baseline. Outcomes Baseline estimated glomerular filtration rate 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 level, myocardial infarction, all-cause mortality, and the composite outcome of myocardial infarction/all-cause mortality. Results Among 3,687 participants, baseline CX3CL1 levels were associated positively with several CVD risk factors and metabolic traits, lower estimated glomerular filtration rate, 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 level also was 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 composite outcomes. In fully adjusted models, 1-SD higher CX3CL1 level 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). Limitations Study design did not allow evaluation of changes over time, correlation with progression of phenotypes, or determination of causality of effect. Conclusions Circulating CX3CL1 level may contribute to both atherosclerotic CVD and diabetes in a CKD cohort. Further studies are required to establish mechanisms through which CX3CL1 affects the pathogenesis of atherosclerosis and diabetes.
KW - Chronic Renal Insufficiency Cohort
KW - Index Words Cardiometabolic disease
KW - atherosclerosis
KW - cardiovascular disease (CVD)
KW - chronic kidney disease (CKD)
KW - diabetes
KW - fractalkine (CX3CL1)
KW - metabolic syndrome
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U2 - 10.1053/j.ajkd.2015.01.021
DO - 10.1053/j.ajkd.2015.01.021
M3 - Article
C2 - 25795074
AN - SCOPUS:84937967994
SN - 0272-6386
VL - 66
SP - 266
EP - 273
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 2
ER -