title: Skin autofluorescence, a non-invasive marker for AGE accumulation, is associated with the degree of atherosclerosis.
abstract: BACKGROUND
  Advanced glycation endproducts (AGEs) may be involved in the development of atherosclerosis, beyond diabetes and renal disease. Skin autofluorescence (AF) is a non-invasive marker for AGEs. We examined whether skin AF is increased in (subclinical) atherosclerosis and associated with the degree of atherosclerosis independent of diabetes and renal function.
  
  
  METHODS
  A cross-sectional study of 223 patients referred for primary (n = 163) or secondary (n = 60) prevention between 2006 and 2012 was performed. Skin AF was measured using the AGE-Reader. Ultrasonography was used to assess plaques in carotid and femoral arteries and computed tomography for the calculation of the coronary artery calcium score (CACS; in primary prevention only). Primary prevention patients were divided into a group with subclinical atherosclerosis defined as >1 plaque or CACS>100 (n = 67; age 53 year [interquartile range 48-56]; 49% male) and without (controls; 96; 43 [38-51]; 55%). Secondary prevention were patients with peripheral arterial disease (60; 64 [58-70]; 73%).
  
  
  RESULTS
  Skin AF was higher in subclinical and clinical atherosclerosis compared with controls (skin AF 2.11 [interquartile range 1.83-2.46] and 2.71 [2.15-3.27] vs. 1.87 [1.68-2.12] respectively; P = 0.005 and <0.001). In a multivariate analysis, the association of skin AF with the atherosclerosis categories was independent of age, sex, diabetes, presence of the metabolic syndrome, Framingham Risk Score, and renal function. Skin AF correlated with most cardiovascular risk factors, Framingham risk score, and IMT and CACS.
  
  
  CONCLUSIONS
  Skin AF is increased in documented subclinical and clinical atherosclerosis, independent of known risk factors such as diabetes and renal disease. These data suggest that AGEs may be associated with the burden of atherosclerosis and warrant a prospective study to investigate its clinical usability as a risk assessment tool for primary prevention.
authors.affiliation: Center for Medical Imaging - North East Netherlands, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands ; Department of Radiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Martijn A M
authors.initials: MA
authors.lastname: den Dekker
authors.affiliation: Department of Internal Medicine, Division of Vascular Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Marjan
authors.initials: M
authors.lastname: Zwiers
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Edwin R
authors.initials: ER
authors.lastname: van den Heuvel
authors.affiliation: Department of Internal Medicine, Division of Vascular Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Lisanne C
authors.initials: LC
authors.lastname: de Vos
authors.affiliation: Department of Internal Medicine, Division of Vascular Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Andries J
authors.initials: AJ
authors.lastname: Smit
authors.affiliation: Department of Surgery, Division of Vascular Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Clark J
authors.initials: CJ
authors.lastname: Zeebregts
authors.affiliation: Center for Medical Imaging - North East Netherlands, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Oudkerk
authors.affiliation: Center for Medical Imaging - North East Netherlands, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands ; Department of Radiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Rozemarijn
authors.initials: R
authors.lastname: Vliegenthart
authors.affiliation: Department of Internal Medicine, Division of Vascular Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Joop D
authors.initials: JD
authors.lastname: Lefrandt
authors.affiliation: Department of Internal Medicine, Division of Vascular Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Douwe J
authors.initials: DJ
authors.lastname: Mulder
mesh_terms: D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D003920:Diabetes Mellitus / Q000378:metabolism / Q000473:pathology; D005260:Female; D017127:Glycation End Products, Advanced / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D061848:Optical Imaging; D058226:Plaque, Atherosclerotic / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D051437:Renal Insufficiency / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D012867:Skin / Q000737:chemistry* / Q000378:metabolism; D014463:Ultrasonography
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced