title: Plasma neutrophil gelatinase-associated lipocalinin in the general population: association with inflammation and prognosis.
abstract: OBJECTIVE
  Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein stored in granules of neutrophil leukocytes participating in inflammatory and atherosclerotic processes and possibly plaque rupture. Despite the putative role of NGAL in atherosclerosis and acute myocardial infarction, human studies of plasma NGAL are still limited.
  
  
  RESULTS
  We prospectively followed 5599 randomly selected men and women from the community in the fourth Copenhagen Heart Study. Plasma NGAL was measured at study entry. Participants were followed for 10 years. During follow-up, 20% died (n=1120) and 15% (n=884) developed a major adverse cardiovascular event. Plasma NGAL associated strongly with all inflammatory markers (high-sensitivity C-reactive protein, total leukocyte count, neutrophil count) and inversely with estimated glomerular filtration rate (all, P<0.001). Multivariate analysis identified neutrophil leukocyte count as the main determinant of plasma NGAL. During follow-up, participants with increasing NGAL had increased risk of all-cause mortality and major adverse cardiovascular event (both, P<0.001). Even after adjustment for confounding risk factors by Cox regression analysis, NGAL remained an independent predictor of both all-cause mortality and major adverse cardiovascular event. When added to the Framingham risk score, NGAL improved c-statistics and correctly reclassified ≈15% into more appropriate risk groups. In comparison with high-sensitivity C-reactive protein, when both markers were added to the Framingham risk score, NGAL conferred 3× to 4× the risk.
  
  
  CONCLUSIONS
  Plasma NGAL is strongly associated with inflammation in the general population. NGAL independently associated with 10-year outcome, and when added to the Framingham risk score, NGAL both improves c-statistics and correctly reclassifies participants into more accurate risk categories.
authors: From the Department of Cardiology P, Gentofte University Hospital, Copenhagen, Denmark (S.L., J.S.J., R.M., S.H.P., S.G.); Copenhagen City Heart Study, Bispebjerg University Hospital, Copenhagen, Denmark (S.L., J.S.J., R.M.); Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark (J.S.J.); The Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark (A.F., N.E.M.); and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark (A.F., N.E.M.). soerenli@hotmail.com.
authors: Søren
authors: S
authors: Lindberg
authors: From the Department of Cardiology P, Gentofte University Hospital, Copenhagen, Denmark (S.L., J.S.J., R.M., S.H.P., S.G.); Copenhagen City Heart Study, Bispebjerg University Hospital, Copenhagen, Denmark (S.L., J.S.J., R.M.); Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark (J.S.J.); The Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark (A.F., N.E.M.); and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark (A.F., N.E.M.).
authors: Jan S
authors: JS
authors: Jensen
authors: From the Department of Cardiology P, Gentofte University Hospital, Copenhagen, Denmark (S.L., J.S.J., R.M., S.H.P., S.G.); Copenhagen City Heart Study, Bispebjerg University Hospital, Copenhagen, Denmark (S.L., J.S.J., R.M.); Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark (J.S.J.); The Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark (A.F., N.E.M.); and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark (A.F., N.E.M.).
authors: Rasmus
authors: R
authors: Mogelvang
authors: From the Department of Cardiology P, Gentofte University Hospital, Copenhagen, Denmark (S.L., J.S.J., R.M., S.H.P., S.G.); Copenhagen City Heart Study, Bispebjerg University Hospital, Copenhagen, Denmark (S.L., J.S.J., R.M.); Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark (J.S.J.); The Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark (A.F., N.E.M.); and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark (A.F., N.E.M.).
authors: Sune H
authors: SH
authors: Pedersen
authors: From the Department of Cardiology P, Gentofte University Hospital, Copenhagen, Denmark (S.L., J.S.J., R.M., S.H.P., S.G.); Copenhagen City Heart Study, Bispebjerg University Hospital, Copenhagen, Denmark (S.L., J.S.J., R.M.); Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark (J.S.J.); The Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark (A.F., N.E.M.); and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark (A.F., N.E.M.).
authors: Søren
authors: S
authors: Galatius
authors: From the Department of Cardiology P, Gentofte University Hospital, Copenhagen, Denmark (S.L., J.S.J., R.M., S.H.P., S.G.); Copenhagen City Heart Study, Bispebjerg University Hospital, Copenhagen, Denmark (S.L., J.S.J., R.M.); Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark (J.S.J.); The Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark (A.F., N.E.M.); and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark (A.F., N.E.M.).
authors: Allan
authors: A
authors: Flyvbjerg
authors: From the Department of Cardiology P, Gentofte University Hospital, Copenhagen, Denmark (S.L., J.S.J., R.M., S.H.P., S.G.); Copenhagen City Heart Study, Bispebjerg University Hospital, Copenhagen, Denmark (S.L., J.S.J., R.M.); Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark (J.S.J.); The Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark (A.F., N.E.M.); and Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark (A.F., N.E.M.).
authors: Nils E
authors: NE
authors: Magnusson
mesh_terms: D000209:Acute-Phase Proteins; D000328:Adult; D000368:Aged; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000453:epidemiology; D015897:Comorbidity; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007249:Inflammation / Q000097:blood*; D018836:Inflammation Mediators / Q000097:blood; D053208:Kaplan-Meier Estimate; D007958:Leukocyte Count; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009504:Neutrophils; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000097:blood*; D018570:Risk Assessment; D012307:Risk Factors; D012494:Sampling Studies
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D018836:Inflammation Mediators; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D002097:C-Reactive Protein
keywords: inflammation