title: Skin autofluorescence is associated with 5-year mortality and cardiovascular events in patients with peripheral artery disease.
abstract: OBJECTIVE
  Advanced glycation end products play a pivotal role in atherosclerosis. Recently, we showed that tissue advanced glycation end products deposition, noninvasively assessed by skin autofluorescence (SAF), is increased in patients with peripheral artery disease. The aim of the present study was to establish whether SAF is associated with all-cause mortality and with fatal or nonfatal major adverse cardiovascular events (MACE) in patients with peripheral artery disease.
  
  
  RESULTS
  We performed a single-center prospective cohort study of 252 patients with peripheral artery disease (mean age, 66±11 years), recruited from the outpatient clinic (October 2007 to June 2008) who were followed until June 2013. SAF was measured with the AGE Reader. The primary end point was all-cause mortality, and the secondary end point was fatal or nonfatal MACE, defined as cardiovascular death and nonfatal myocardial infarction or stroke. During a median follow-up of 5.1 (interquartile range, 5.0-5.3) years, 62 (25%) patients died. Fatal or nonfatal MACE occurred in 62 (25%) patients. A higher SAF was associated with increased risk for all-cause mortality (hazard ratio per unit increase, 2.01; 95% confidence interval, 1.40-2.88; P=0.0002) and fatal or nonfatal MACE (hazard ratio, 1.82; 95% confidence interval, 1.28-2.60; P=0.001), also after adjustment for cardiovascular risk factors and the use of lipid-lowering drugs (hazard ratio, 1.63; 95% confidence interval, 1.13-2.34; P=0.009 and hazard ratio, 1.50; 95% confidence interval, 1.04-2.17; P=0.03, for all-cause mortality and fatal and nonfatal MACE, respectively).
  
  
  CONCLUSIONS
  SAF as a measure of advanced glycation end products deposition is independently associated with all-cause mortality and fatal or nonfatal MACE in patients with peripheral artery disease after a 5-year follow-up.
authors: From the Department of Internal Medicine, Division of Vascular Medicine (L.C.d.V., D.J.M., A.J.S., P.W.K., J.D.L.), Division of Endocrinology (R.P.F.D.), and Department of Surgery, Division of Vascular Medicine (C.J.Z.), The Diabetes Centre, Isala, Zwolle (N.K.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; and Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands (W.M.L.).
authors: Lisanne C
authors: LC
authors: de Vos
authors: Douwe J
authors: DJ
authors: Mulder
authors: Andries J
authors: AJ
authors: Smit
authors: Robin P F
authors: RP
authors: Dullaart
authors: Nanne
authors: N
authors: Kleefstra
authors: Willem M
authors: WM
authors: Lijfering
authors: Pieter W
authors: PW
authors: Kamphuisen
authors: Clark J
authors: CJ
authors: Zeebregts
authors: Joop D
authors: JD
authors: Lefrandt
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism / Q000401:mortality; D009426:Netherlands / Q000453:epidemiology; D058729:Peripheral Arterial Disease / Q000378:metabolism* / Q000401:mortality*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D012867:Skin / Q000378:metabolism*; D020521:Stroke / Q000378:metabolism / Q000401:mortality; D013997:Time Factors
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced
keywords: advanced glycation end products; atherosclerosis; cardiovascular diseases; peripheral artery disease