title: Elevated plasma YKL-40, lipids and lipoproteins, and ischemic vascular disease in the general population.
abstract: OBJECTIVE
  We tested the hypothesis that observationally and genetically elevated YKL-40 is associated with elevated lipids and lipoproteins and with increased risk of ischemic vascular disease.
  
  
  METHODS
  We conducted cohort and Mendelian randomization studies in 96 110 individuals from the Danish general population, with measured plasma levels of YKL-40 (n=21 647), plasma lipids and lipoproteins (n=94 461), and CHI3L1 rs4950928 genotype (n=94 579).
  
  
  RESULTS
  From 1977 to 2013, 3256 individuals developed ischemic stroke, 5629 ischemic cerebrovascular disease, 4183 myocardial infarction, and 10 271 developed ischemic heart disease. The 91% to 100% versus 0% to 33% YKL-40 percentile category was associated with a 34% increase in triglycerides, but only with minor changes in other lipids and lipoproteins. For these categories, the multifactorially adjusted hazard ratio was 1.99 (95% confidence interval, 1.49-2.67) for ischemic stroke, 1.85 (1.44-2.37) for ischemic cerebrovascular disease, 1.28 (0.95-1.73) for myocardial infarction, and 1.23 (1.01-1.51) for ischemic heart disease. When compared with rs4950928 CC homozygosity, the presence of G-allele was associated with a doubling (GC) or tripling (GG) in YKL-40 levels, but not with triglyceride levels or with risk of ischemic vascular disease. A doubling in YKL-40 was associated with a multifactorially adjusted observational hazard ratio for ischemic stroke of 1.18 (1.11-1.27), and a genetic odds ratio of 1.04 (0.95-1.15). Corresponding risk estimates were 1.15 (1.09-1.22) observationally and 1.06 (0.99-1.14) genetically for ischemic cerebrovascular disease, 1.08 (1.00-1.15) observationally and 1.04 (0.96-1.13) genetically for myocardial infarction, and 1.07 (1.02-1.12) observationally and 1.01 (0.96-1.07) genetically for ischemic heart disease.
  
  
  CONCLUSIONS
  Elevated YKL-40 was associated with a 34% increase in triglyceride levels and with a 2-fold increased risk of ischemic stroke, whereas genetically elevated YKL-40 were not.
authors.affiliation: From the Copenhagen General Population Study, Department of Clinical Biochemistry (A.D.K., S.E.B., B.G.N.), and Department of Medicine and Oncology (J.S.J.), Herlev University Hospital, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (A.D.K., J.S.J., S.E.B., B.G.N.); and The Copenhagen City Heart Study, Frederiksberg University Hospital, Frederiksberg, Denmark (S.E.B., B.G.N.).
authors.forename: Alisa D
authors.initials: AD
authors.lastname: Kjaergaard
authors.affiliation: From the Copenhagen General Population Study, Department of Clinical Biochemistry (A.D.K., S.E.B., B.G.N.), and Department of Medicine and Oncology (J.S.J.), Herlev University Hospital, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (A.D.K., J.S.J., S.E.B., B.G.N.); and The Copenhagen City Heart Study, Frederiksberg University Hospital, Frederiksberg, Denmark (S.E.B., B.G.N.).
authors.forename: Julia S
authors.initials: JS
authors.lastname: Johansen
authors.affiliation: From the Copenhagen General Population Study, Department of Clinical Biochemistry (A.D.K., S.E.B., B.G.N.), and Department of Medicine and Oncology (J.S.J.), Herlev University Hospital, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (A.D.K., J.S.J., S.E.B., B.G.N.); and The Copenhagen City Heart Study, Frederiksberg University Hospital, Frederiksberg, Denmark (S.E.B., B.G.N.).
authors.forename: Stig E
authors.initials: SE
authors.lastname: Bojesen
authors.affiliation: From the Copenhagen General Population Study, Department of Clinical Biochemistry (A.D.K., S.E.B., B.G.N.), and Department of Medicine and Oncology (J.S.J.), Herlev University Hospital, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (A.D.K., J.S.J., S.E.B., B.G.N.); and The Copenhagen City Heart Study, Frederiksberg University Hospital, Frederiksberg, Denmark (S.E.B., B.G.N.). boerge.nordestgaard@regionh.dk.
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
mesh_terms: D054392:Adipokines / Q000097:blood*; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002561:Cerebrovascular Disorders / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology; D000071451:Chitinase-3-Like Protein 1; D015331:Cohort Studies; D005260:Female; D006801:Humans; D037102:Lectins / Q000097:blood*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction; D017202:Myocardial Ischemia / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D011159:Population Surveillance; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D014280:Triglycerides / Q000097:blood*; D014652:Vascular Diseases / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology
chemical_list: D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; D008055:Lipids; D008074:Lipoproteins; D014280:Triglycerides
keywords: YKL-40 protein, human; brain ischemia; molecular epidemiology; myocardial ischemia; triglycerides