title: Skin Autofluorescence and Pentosidine Are Associated With Aortic Stiffening: The Maastricht Study.
abstract: Arterial stiffening, as characterized by an increase in carotid-femoral pulse-wave velocity or pulse pressure, increases the risk of cardiovascular disease, especially among individuals with type 2 diabetes mellitus. Advanced glycation end products are hypothesized to play a role in the development of arterial stiffness. Therefore, we investigated the association between skin autofluorescence, an estimate of tissue advanced glycation end products, and plasma advanced glycation end products on the one hand and arterial stiffening on the other in 862 participants of The Maastricht Study (mean age of 60 years; 45% women) with normal glucose metabolism (n=469), impaired glucose metabolism (n=140), or type 2 diabetes (n=253). Associations were analyzed with linear regression analysis and adjusted for potential confounders. We found that higher skin autofluorescence as measured by the AGE Reader and plasma pentosidine were independently associated with higher carotid-femoral pulse-wave velocity (sβ 0.10; 95% confidence interval, 0.03-0.17 and 0.10; 0.04-0.16, respectively) and central pulse pressure (sβ 0.08; 95% confidence interval 0.01-0.15 and 0.07; 0.01-0.13, respectively). The associations between skin autofluorescence and pentosidine, and carotid-femoral pulse-wave velocity were more pronounced in individuals with type 2 diabetes mellitus (P-interaction<0.10). These results support the hypothesis that accumulation of advanced glycation end products is involved in arterial stiffening and may explain part of the increased risk of cardiovascular disease in individuals with type 2 diabetes mellitus.
authors.affiliation: From the Department of Internal Medicine (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); Department of Epidemiology (P.C.D.); Department of Social Medicine (A.K.); Cardiovascular Research Institute Maastricht (CARIM) (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., P.C.D., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands (P.C.D., A.K., N.S., C.D.A.S.); and Department of Internal Medicine, Division of Vascular Medicine, University Medical Center Groningen, University of Groningen, The Netherlands (A.J.S.).
authors.forename: Marcelle G A
authors.initials: MG
authors.lastname: van Eupen
authors.affiliation: From the Department of Internal Medicine (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); Department of Epidemiology (P.C.D.); Department of Social Medicine (A.K.); Cardiovascular Research Institute Maastricht (CARIM) (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., P.C.D., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands (P.C.D., A.K., N.S., C.D.A.S.); and Department of Internal Medicine, Division of Vascular Medicine, University Medical Center Groningen, University of Groningen, The Netherlands (A.J.S.).
authors.forename: Miranda T
authors.initials: MT
authors.lastname: Schram
authors.affiliation: From the Department of Internal Medicine (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); Department of Epidemiology (P.C.D.); Department of Social Medicine (A.K.); Cardiovascular Research Institute Maastricht (CARIM) (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., P.C.D., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands (P.C.D., A.K., N.S., C.D.A.S.); and Department of Internal Medicine, Division of Vascular Medicine, University Medical Center Groningen, University of Groningen, The Netherlands (A.J.S.).
authors.forename: Thomas T
authors.initials: TT
authors.lastname: van Sloten
authors.affiliation: From the Department of Internal Medicine (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); Department of Epidemiology (P.C.D.); Department of Social Medicine (A.K.); Cardiovascular Research Institute Maastricht (CARIM) (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., P.C.D., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands (P.C.D., A.K., N.S., C.D.A.S.); and Department of Internal Medicine, Division of Vascular Medicine, University Medical Center Groningen, University of Groningen, The Netherlands (A.J.S.).
authors.forename: Jean
authors.initials: J
authors.lastname: Scheijen
authors.affiliation: From the Department of Internal Medicine (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); Department of Epidemiology (P.C.D.); Department of Social Medicine (A.K.); Cardiovascular Research Institute Maastricht (CARIM) (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., P.C.D., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands (P.C.D., A.K., N.S., C.D.A.S.); and Department of Internal Medicine, Division of Vascular Medicine, University Medical Center Groningen, University of Groningen, The Netherlands (A.J.S.).
authors.forename: Simone J S
authors.initials: SJ
authors.lastname: Sep
authors.affiliation: From the Department of Internal Medicine (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); Department of Epidemiology (P.C.D.); Department of Social Medicine (A.K.); Cardiovascular Research Institute Maastricht (CARIM) (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., P.C.D., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands (P.C.D., A.K., N.S., C.D.A.S.); and Department of Internal Medicine, Division of Vascular Medicine, University Medical Center Groningen, University of Groningen, The Netherlands (A.J.S.).
authors.forename: Carla J
authors.initials: CJ
authors.lastname: van der Kallen
authors.affiliation: From the Department of Internal Medicine (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); Department of Epidemiology (P.C.D.); Department of Social Medicine (A.K.); Cardiovascular Research Institute Maastricht (CARIM) (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., P.C.D., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands (P.C.D., A.K., N.S., C.D.A.S.); and Department of Internal Medicine, Division of Vascular Medicine, University Medical Center Groningen, University of Groningen, The Netherlands (A.J.S.).
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dagnelie
authors.affiliation: From the Department of Internal Medicine (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); Department of Epidemiology (P.C.D.); Department of Social Medicine (A.K.); Cardiovascular Research Institute Maastricht (CARIM) (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., P.C.D., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands (P.C.D., A.K., N.S., C.D.A.S.); and Department of Internal Medicine, Division of Vascular Medicine, University Medical Center Groningen, University of Groningen, The Netherlands (A.J.S.).
authors.forename: Annemarie
authors.initials: A
authors.lastname: Koster
authors.affiliation: From the Department of Internal Medicine (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); Department of Epidemiology (P.C.D.); Department of Social Medicine (A.K.); Cardiovascular Research Institute Maastricht (CARIM) (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., P.C.D., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands (P.C.D., A.K., N.S., C.D.A.S.); and Department of Internal Medicine, Division of Vascular Medicine, University Medical Center Groningen, University of Groningen, The Netherlands (A.J.S.).
authors.forename: Nicolaas
authors.initials: N
authors.lastname: Schaper
authors.affiliation: From the Department of Internal Medicine (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); Department of Epidemiology (P.C.D.); Department of Social Medicine (A.K.); Cardiovascular Research Institute Maastricht (CARIM) (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., P.C.D., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands (P.C.D., A.K., N.S., C.D.A.S.); and Department of Internal Medicine, Division of Vascular Medicine, University Medical Center Groningen, University of Groningen, The Netherlands (A.J.S.).
authors.forename: Ronald M A
authors.initials: RM
authors.lastname: Henry
authors.affiliation: From the Department of Internal Medicine (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); Department of Epidemiology (P.C.D.); Department of Social Medicine (A.K.); Cardiovascular Research Institute Maastricht (CARIM) (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., P.C.D., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands (P.C.D., A.K., N.S., C.D.A.S.); and Department of Internal Medicine, Division of Vascular Medicine, University Medical Center Groningen, University of Groningen, The Netherlands (A.J.S.).
authors.forename: Abraham A
authors.initials: AA
authors.lastname: Kroon
authors.affiliation: From the Department of Internal Medicine (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); Department of Epidemiology (P.C.D.); Department of Social Medicine (A.K.); Cardiovascular Research Institute Maastricht (CARIM) (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., P.C.D., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands (P.C.D., A.K., N.S., C.D.A.S.); and Department of Internal Medicine, Division of Vascular Medicine, University Medical Center Groningen, University of Groningen, The Netherlands (A.J.S.).
authors.forename: Andries J
authors.initials: AJ
authors.lastname: Smit
authors.affiliation: From the Department of Internal Medicine (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); Department of Epidemiology (P.C.D.); Department of Social Medicine (A.K.); Cardiovascular Research Institute Maastricht (CARIM) (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., P.C.D., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands (P.C.D., A.K., N.S., C.D.A.S.); and Department of Internal Medicine, Division of Vascular Medicine, University Medical Center Groningen, University of Groningen, The Netherlands (A.J.S.).
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
authors.affiliation: From the Department of Internal Medicine (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); Department of Epidemiology (P.C.D.); Department of Social Medicine (A.K.); Cardiovascular Research Institute Maastricht (CARIM) (M.G.A.v.E., M.T.S., T.T.v.S., J.S., S.J.S.S., C.J.v.d.K., P.C.D., N.S., R.M.A.H., A.A.K., C.D.A.S., C.G.S.); School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands (P.C.D., A.K., N.S., C.D.A.S.); and Department of Internal Medicine, Division of Vascular Medicine, University Medical Center Groningen, University of Groningen, The Netherlands (A.J.S.). c.schalkwijk@maastrichtuniversity.nl.
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000503:physiopathology; D016009:Chi-Square Distribution; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D016014:Linear Models; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008875:Middle Aged; D061848:Optical Imaging / Q000379:methods; D011446:Prospective Studies; D063177:Pulse Wave Analysis; D012867:Skin / Q000098:blood supply / Q000378:metabolism*; D059289:Vascular Stiffness / Q000187:drug effects* / Q000502:physiology
chemical_list: D001120:Arginine; D005947:Glucose; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D008239:Lysine; C062187:pentosidine
keywords: advanced glycation end products; arterial stiffness autofluorescence imaging; blood pressure; pentosidine