Nehal N Mehta1, Gregory J Matthews2, Parasuram Krishnamoorthy3, Rhia Shah3, Catherine McLaughlin3, Parth Patel3, Matthew Budoff4, Jing Chen5, Melanie Wolman6, Alan Go7, Jiang He5, Peter A Kanetsky6, Stephen R Master8, Daniel J Rader3, Dominic Raj9, Crystal A Gadegbeku10, Rachana Shah11, Marty Schreiber12, Michael J Fischer13, Raymond R Townsend14, John Kusek15, Harold I Feldman16, Andrea S Foulkes2, Muredach P Reilly17. 1. National Heart, Lung and Blood Institute, Bethesda, MD, USA nehal.mehta@nih.gov muredach@mail.med.upenn.edu. 2. School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA, USA. 3. Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 4. Los Angeles Biomedical Research Institute, Torrancem, CA, USA. 5. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA. 6. Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 7. Division of Research, Kaiser Permanente of Northern California, Oakland, CA, USA. 8. Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 9. The George Washington University, Washington, DC, USA. 10. Department of Medicine, Temple University School of Medicine, Philadelphia, PA, USA. 11. Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA, USA. 12. Cleveland Clinic Foundation, Cleveland, OH, USA. 13. 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. 14. Renal Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 15. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, MD, USA. 16. 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. 17. Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA nehal.mehta@nih.gov muredach@mail.med.upenn.edu.
Abstract
AIMS: 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. METHODS AND 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. Published by Oxford University Press on behalf of the European Society of Cardiology 2013. This work is written by (a) US Government employee(s) and is in the public domain in the US.
AIMS: 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. METHODS AND 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. Published by Oxford University Press on behalf of the European Society of Cardiology 2013. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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