title: YKL-40 is elevated in patients with peripheral arterial disease and diabetes or pre-diabetes.
abstract: OBJECTIVE
  YKL-40 is secreted by macrophages in atherosclerotic lesions and involved in plaque rupture. YKL-40 is elevated in coronary artery disease, and predicts cardiovascular mortality. Experimental in vivo and in vitro data suggest a role of YKL-40 in tissue remodeling. A disease modulating potency of YKL-40 was not investigated in peripheral arterial disease (PAD).
  
  
  METHODS
  We measured YKL-40 in 460 subjects: 316 PAD: 71 normal glucose metabolism (PAD-NGM), 90 pre-diabetes (PAD-PREDM) and 155 diabetes (PAD-DM); 20 diabetes with atherosclerosis but without PAD (AS-DM); 85 diabetes without macro-vascular complications (DM) and 39 healthy controls (CO).
  
  
  RESULTS
  YKL-40 is higher in PAD vs. CO (median [25-75 percentile]: 103 [69-159] vs. 43 [30-80]ng/ml; p<0.001). In addition, YKL-40 is elevated in DM (p<0.001), PAD-NGM (p=0.001), PAD-PREDM (p<0.001), PAD-DM (p<0.001) and AS-DM (p=0.002) compared to CO. Among PAD, YKL-40 is increased in PAD-PREDM (p=0.001) and PAD-DM (p=0.01) vs. PAD-NGM. By multivariate regression YKL-40 is significantly associated with age (beta=0.272), triglycerides (beta=0.216), aspartate-amino-transferase (beta=0.177) and c-reactive-protein (beta=0.178). Underpinning its role YKL-40 was found to be associated with micro-/macroalbuminuria (p=0.014/p=008)--a strong remodeling inducer. In addition, YKL-40 was elevated in existence of mediasclerosis (p=0.008), a remodeling process.
  
  
  CONCLUSIONS
  We are first to show that YKL-40 is higher in subjects with peripheral arterial disease. YKL-40 was higher in PAD patients with pre-/diabetes. In addition, YKL-40 was associated with the "severity" of generalized atherosclerosis estimated by affected vascular beds. All our findings point towards a role of YKL-40 in the progression/prognosis of patients with PAD and concomitant diabetes.
authors.affiliation: Division of Pediatric Cardiology, University Zurich, Switzerland.
authors.forename: Klaudija
authors.initials: K
authors.lastname: Batinic
authors.forename: Clemens
authors.initials: C
authors.lastname: Höbaus
authors.forename: Milan
authors.initials: M
authors.lastname: Grujicic
authors.forename: Angelika
authors.initials: A
authors.lastname: Steffan
authors.forename: Finka
authors.initials: F
authors.lastname: Jelic
authors.forename: David
authors.initials: D
authors.lastname: Lorant
authors.forename: Thomas
authors.initials: T
authors.lastname: Hörtenhuber
authors.forename: Florian
authors.initials: F
authors.lastname: Hoellerl
authors.forename: Johanna-Maria
authors.initials: JM
authors.lastname: Brix
authors.forename: Guntram
authors.initials: G
authors.lastname: Schernthaner
authors.forename: Renate
authors.initials: R
authors.lastname: Koppensteiner
authors.forename: Gerit-Holger
authors.initials: GH
authors.lastname: Schernthaner
mesh_terms: D054392:Adipokines / Q000097:blood*; D000328:Adult; D000368:Aged; D001317:Austria / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D016009:Chi-Square Distribution; D000071451:Chitinase-3-Like Protein 1; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D006801:Humans; D037102:Lectins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D058729:Peripheral Arterial Disease / Q000097:blood* / Q000453:epidemiology; D011236:Prediabetic State / Q000097:blood* / Q000453:epidemiology; D011379:Prognosis; D012044:Regression Analysis; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D015854:Up-Regulation
chemical_list: D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; D002097:C-Reactive Protein