title: Traditional and non-traditional risk factors for incident peripheral arterial disease among patients with chronic kidney disease.
abstract: The risk of peripheral arterial disease (PAD) is higher in patients with chronic kidney disease (CKD) compared with those without. However, reasons for this increased risk are not fully understood.
  
  
  
  We studied risk factors for incident PAD among 3169 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study. Patients with CKD aged 21-74 years were recruited between 2003 and 2008 and followed for a median of 6.3 years. Incident PAD was defined as a new onset ankle-brachial index (ABI) of <0.9 or confirmed clinical PAD.
  
  
  
  In a multivariate-adjusted model, older age, female sex, non-Hispanic Black, current smoking, diabetes, higher pulse pressure, lower high-density lipoprotein cholesterol, higher low-density lipoprotein cholesterol, and lower estimated glomerular filtration rate were significantly associated with the increased risk of incident PAD. After adjustment for these traditional risk factors as well as use of medications and CRIC Study clinic sites, the following baseline novel risk factors were significantly associated with risk of incident PAD [hazard ratio and 95% confidence interval (CI) for a one standard deviation (SD) higher level]: log[C-reactive protein (CRP)] (1.16, 1.06-1.25, P < 0.001), white blood cell count (1.09, 1.01-1.18, P = 0.03), fibrinogen (1.15, 1.06-1.26, P = 0.002), log(myeloperoxidase) (1.12, 1.03-1.23, P = 0.01), uric acid (0.88, 0.80-0.97, P = 0.01), glycated hemoglobin (1.16, 1.05-1.27, P = 0.003), log(homeostatic model assessment-insulin resistance) (1.21, 1.10-1.32, P < 0.001) and alkaline phosphatase (1.15, 1.07-1.24, P < 0.001).
  
  
  
  Among patients with CKD, inflammation, prothrombotic state, oxidative stress, glycated hemoglobin, insulin resistance and alkaline phosphatase are associated with an increased risk of PAD, independent of traditional risk factors.
authors.affiliation: Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA 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: Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Emile R
authors.initials: ER
authors.lastname: Mohler
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Dawei
authors.initials: D
authors.lastname: Xie
authors.affiliation: Department of Medicine, University of California at San Francisco School of Medicine, San Francisco, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Shlipak
authors.affiliation: Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Townsend
authors.affiliation: Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Appel
authors.affiliation: Department of Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA.
authors.forename: Akinlolu
authors.initials: A
authors.lastname: Ojo
authors.affiliation: Department of Nephrology and Hypertension, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Schreiber
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Nessel
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Medicine, George Washington University School of Medicine, Washington, DC, USA.
authors.forename: Dominic
authors.initials: D
authors.lastname: Raj
authors.affiliation: Department of Medicine, Case Western University, Cleveland, OH, USA.
authors.forename: Louise
authors.initials: L
authors.lastname: Strauss
authors.affiliation: Department of Medicine, University of Illinois College of Medicine, Chicago, IL, USA.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Lora
authors.affiliation: Department of Medicine, Case Western University, Cleveland, OH, USA.
authors.forename: Mahboob
authors.initials: M
authors.lastname: Rahman
authors.affiliation: Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: L Lee
authors.initials: LL
authors.lastname: Hamm
authors.affiliation: Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA 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
mesh_terms: D001741:Black or African American; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D055109:Ankle Brachial Index; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D058729:Peripheral Arterial Disease / Q000097:blood / Q000453:epidemiology* / Q000208:ethnology; D016016:Proportional Hazards Models; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000453:epidemiology* / Q000208:ethnology; D012307:Risk Factors; D017678:Sex Distribution
chemical_list: D000469:Alkaline Phosphatase; D002097:C-Reactive Protein; D006442:Glycated Hemoglobin; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL
keywords: chronic kidney disease; novel risk factors; peripheral arterial disease; traditional risk factors