title: Higher plasma CXCL12 levels predict incident myocardial infarction and death in chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort study.
abstract: OBJECTIVE
  Genome-wide association studies revealed an association between a locus at 10q11, downstream from CXCL12, and myocardial infarction (MI). However, the relationship among plasma CXCL12, cardiovascular disease (CVD) risk factors, incident MI, and death is unknown.
  
  
  RESULTS
  We analysed study-entry plasma CXCL12 levels in 3687 participants of the Chronic Renal Insufficiency Cohort (CRIC) Study, a prospective study of cardiovascular and kidney outcomes in chronic kidney disease (CKD) patients. Mean follow-up was 6 years for incident MI or death. Plasma CXCL12 levels were positively associated with several cardiovascular risk factors (age, hypertension, diabetes, hypercholesterolaemia), lower estimated glomerular filtration rate (eGFR), and higher inflammatory cytokine levels (P < 0.05). In fully adjusted models, higher study-entry CXCL12 was associated with increased odds of prevalent CVD (OR 1.23; 95% confidence interval 1.14, 1.33, P < 0.001) for one standard deviation (SD) increase in CXCL12. Similarly, one SD higher CXCL12 increased the hazard of incident MI (1.26; 1.09,1.45, P < 0.001), death (1.20; 1.09,1.33, P < 0.001), and combined MI/death (1.23; 1.13-1.34, P < 0.001) adjusting for demographic factors, known CVD risk factors, and inflammatory markers and remained significant for MI (1.19; 1.03,1.39, P = 0.01) and the combined MI/death (1.13; 1.03,1.24, P = 0.01) after further controlling for eGFR and urinary albumin:creatinine ratio.
  
  
  CONCLUSIONS
  In CKD, higher plasma CXCL12 was associated with CVD risk factors and prevalent CVD as well as the hazard of incident MI and death. Further studies are required to establish if plasma CXCL12 reflect causal actions at the vessel wall and is a tool for genomic and therapeutic trials.
authors.affiliation: National Heart, Lung and Blood Institute, Bethesda, MD, USA nehal.mehta@nih.gov muredach@mail.med.upenn.edu.
authors.forename: Nehal N
authors.initials: NN
authors.lastname: Mehta
authors.affiliation: School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Matthews
authors.affiliation: Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Parasuram
authors.initials: P
authors.lastname: Krishnamoorthy
authors.affiliation: Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Rhia
authors.initials: R
authors.lastname: Shah
authors.affiliation: Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: McLaughlin
authors.affiliation: Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Parth
authors.initials: P
authors.lastname: Patel
authors.affiliation: Los Angeles Biomedical Research Institute, Torrancem, CA, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Budoff
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Wolman
authors.affiliation: Division of Research, Kaiser Permanente of Northern California, Oakland, CA, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Go
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kanetsky
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Master
authors.affiliation: Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
authors.affiliation: The George Washington University, Washington, DC, USA.
authors.forename: Dominic
authors.initials: D
authors.lastname: Raj
authors.affiliation: Department of Medicine, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Crystal A
authors.initials: CA
authors.lastname: Gadegbeku
authors.affiliation: Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Rachana
authors.initials: R
authors.lastname: Shah
authors.affiliation: Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: Marty
authors.initials: M
authors.lastname: Schreiber
authors.affiliation: Department of Medicine, Jesse Brown VA Medical Center and University of Hospital and Health Sciences System, Chicago, IL, USA Center for Management of Complex Chronic Care, Edward Hines Jr., VA Hospital, Hines, IL, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Fischer
authors.affiliation: Renal Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Townsend
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, MD, USA.
authors.forename: John
authors.initials: J
authors.lastname: Kusek
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA Renal Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Harold I
authors.initials: HI
authors.lastname: Feldman
authors.affiliation: School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA, USA.
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Foulkes
authors.affiliation: Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA nehal.mehta@nih.gov muredach@mail.med.upenn.edu.
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D033162:Incidental Findings; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000175:diagnosis*; D011379:Prognosis; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000401:mortality*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D054377:Chemokine CXCL12
keywords: Atherosclerosis; CXCL12; Chemokines; Myocardial infarction