title: Circulating N-Linked Glycoprotein Acetyls and Longitudinal Mortality Risk.
abstract: BACKGROUND
  Circulating glycoprotein N-acetyl glucosamine residues have recently been associated with incident cardiovascular disease and diabetes mellitus.
  
  
  OBJECTIVE
  Using a plasma glycan biosignature (GlycA) to identify circulating N-acetyl glycan groups, we examined the longitudinal association between GlycA and mortality among initially healthy individuals.
  
  
  RESULTS
  We quantified GlycA by 400 MHz (1)H nuclear magnetic resonance spectroscopy in 27,524 participants in the Women's Health Study (NCT00000479). The primary outcome was all-cause mortality. We replicated the findings in an independent cohort of 12,527 individuals in the Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial (NCT00239681). We also undertook secondary examination of cardiovascular disease and cancer mortality in the Women's Health Study. In the Women's Health Study, during 524,515 person-years of follow-up (median, 20.5 years), there were 3523 deaths. Risk factor-adjusted multivariable Cox proportional hazard ratio (95% confidence interval) per SD increment in GlycA for all-cause mortality was significantly increased at 5 years (1.21 [1.06-1.40]) and during maximal follow-up (1.14 [1.09-1.16]). Similar risk for all-cause mortality was observed in the replication cohort (1.33 [1.21-1.45]). In the Women's Health Study, risk of cardiovascular disease mortality was increased at 5 years (1.43 [1.05-1.95]) and during maximal follow-up (1.15 [1.04-1.26]) and of cancer mortality at 5 years (1.23 [1.02-1.47]) and during maximal follow-up (1.08 [1.01-1.16]). Examination of correlations and mortality associations adjusted for high-sensitivity C-reactive protein, fibrinogen, and intercellular adhesion molecule-1, suggested that GlycA reflects summative risk related to multiple pathways of systemic inflammation.
  
  
  CONCLUSIONS
  Among initially healthy individuals, elevated baseline circulating glycoprotein N-acetyl methyl groups were associated with longitudinal risk of all-cause, cardiovascular, and cancer mortality.
authors.affiliation: From the Center for Lipid Metabolomics (P.R.L., A.O.A., S.M.), the Cardiovascular Division (P.R.L., P.MR., S.M.) and Division of Preventive Medicine (P.R.L., A.O.A., P.D.C., M.V.M., M.J.V., I.-M.L., R.J.G., P.MR., J.E.B., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Harvard Chan School of Public Health, Boston, MA (P.R.L., I-M.L., R.J.G., P.MR., J.E.B.), and Department of Ophthalmology and Visual Sciences, Center for Translational Medicine, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City (D.A.S.).
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Lawler
authors.affiliation: From the Center for Lipid Metabolomics (P.R.L., A.O.A., S.M.), the Cardiovascular Division (P.R.L., P.MR., S.M.) and Division of Preventive Medicine (P.R.L., A.O.A., P.D.C., M.V.M., M.J.V., I.-M.L., R.J.G., P.MR., J.E.B., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Harvard Chan School of Public Health, Boston, MA (P.R.L., I-M.L., R.J.G., P.MR., J.E.B.), and Department of Ophthalmology and Visual Sciences, Center for Translational Medicine, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City (D.A.S.).
authors.forename: Akintunde O
authors.initials: AO
authors.lastname: Akinkuolie
authors.affiliation: From the Center for Lipid Metabolomics (P.R.L., A.O.A., S.M.), the Cardiovascular Division (P.R.L., P.MR., S.M.) and Division of Preventive Medicine (P.R.L., A.O.A., P.D.C., M.V.M., M.J.V., I.-M.L., R.J.G., P.MR., J.E.B., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Harvard Chan School of Public Health, Boston, MA (P.R.L., I-M.L., R.J.G., P.MR., J.E.B.), and Department of Ophthalmology and Visual Sciences, Center for Translational Medicine, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City (D.A.S.).
authors.forename: Paulette D
authors.initials: PD
authors.lastname: Chandler
authors.affiliation: From the Center for Lipid Metabolomics (P.R.L., A.O.A., S.M.), the Cardiovascular Division (P.R.L., P.MR., S.M.) and Division of Preventive Medicine (P.R.L., A.O.A., P.D.C., M.V.M., M.J.V., I.-M.L., R.J.G., P.MR., J.E.B., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Harvard Chan School of Public Health, Boston, MA (P.R.L., I-M.L., R.J.G., P.MR., J.E.B.), and Department of Ophthalmology and Visual Sciences, Center for Translational Medicine, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City (D.A.S.).
authors.forename: M Vinayaga
authors.initials: MV
authors.lastname: Moorthy
authors.affiliation: From the Center for Lipid Metabolomics (P.R.L., A.O.A., S.M.), the Cardiovascular Division (P.R.L., P.MR., S.M.) and Division of Preventive Medicine (P.R.L., A.O.A., P.D.C., M.V.M., M.J.V., I.-M.L., R.J.G., P.MR., J.E.B., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Harvard Chan School of Public Health, Boston, MA (P.R.L., I-M.L., R.J.G., P.MR., J.E.B.), and Department of Ophthalmology and Visual Sciences, Center for Translational Medicine, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City (D.A.S.).
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Vandenburgh
authors.affiliation: From the Center for Lipid Metabolomics (P.R.L., A.O.A., S.M.), the Cardiovascular Division (P.R.L., P.MR., S.M.) and Division of Preventive Medicine (P.R.L., A.O.A., P.D.C., M.V.M., M.J.V., I.-M.L., R.J.G., P.MR., J.E.B., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Harvard Chan School of Public Health, Boston, MA (P.R.L., I-M.L., R.J.G., P.MR., J.E.B.), and Department of Ophthalmology and Visual Sciences, Center for Translational Medicine, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City (D.A.S.).
authors.forename: Debra A
authors.initials: DA
authors.lastname: Schaumberg
authors.affiliation: From the Center for Lipid Metabolomics (P.R.L., A.O.A., S.M.), the Cardiovascular Division (P.R.L., P.MR., S.M.) and Division of Preventive Medicine (P.R.L., A.O.A., P.D.C., M.V.M., M.J.V., I.-M.L., R.J.G., P.MR., J.E.B., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Harvard Chan School of Public Health, Boston, MA (P.R.L., I-M.L., R.J.G., P.MR., J.E.B.), and Department of Ophthalmology and Visual Sciences, Center for Translational Medicine, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City (D.A.S.).
authors.forename: I-Min
authors.initials: IM
authors.lastname: Lee
authors.affiliation: From the Center for Lipid Metabolomics (P.R.L., A.O.A., S.M.), the Cardiovascular Division (P.R.L., P.MR., S.M.) and Division of Preventive Medicine (P.R.L., A.O.A., P.D.C., M.V.M., M.J.V., I.-M.L., R.J.G., P.MR., J.E.B., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Harvard Chan School of Public Health, Boston, MA (P.R.L., I-M.L., R.J.G., P.MR., J.E.B.), and Department of Ophthalmology and Visual Sciences, Center for Translational Medicine, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City (D.A.S.).
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Glynn
authors.affiliation: From the Center for Lipid Metabolomics (P.R.L., A.O.A., S.M.), the Cardiovascular Division (P.R.L., P.MR., S.M.) and Division of Preventive Medicine (P.R.L., A.O.A., P.D.C., M.V.M., M.J.V., I.-M.L., R.J.G., P.MR., J.E.B., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Harvard Chan School of Public Health, Boston, MA (P.R.L., I-M.L., R.J.G., P.MR., J.E.B.), and Department of Ophthalmology and Visual Sciences, Center for Translational Medicine, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City (D.A.S.).
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.affiliation: From the Center for Lipid Metabolomics (P.R.L., A.O.A., S.M.), the Cardiovascular Division (P.R.L., P.MR., S.M.) and Division of Preventive Medicine (P.R.L., A.O.A., P.D.C., M.V.M., M.J.V., I.-M.L., R.J.G., P.MR., J.E.B., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Harvard Chan School of Public Health, Boston, MA (P.R.L., I-M.L., R.J.G., P.MR., J.E.B.), and Department of Ophthalmology and Visual Sciences, Center for Translational Medicine, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City (D.A.S.).
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.affiliation: From the Center for Lipid Metabolomics (P.R.L., A.O.A., S.M.), the Cardiovascular Division (P.R.L., P.MR., S.M.) and Division of Preventive Medicine (P.R.L., A.O.A., P.D.C., M.V.M., M.J.V., I.-M.L., R.J.G., P.MR., J.E.B., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Harvard Chan School of Public Health, Boston, MA (P.R.L., I-M.L., R.J.G., P.MR., J.E.B.), and Department of Ophthalmology and Visual Sciences, Center for Translational Medicine, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City (D.A.S.). smora@partners.org.
authors.forename: Samia
authors.initials: S
authors.lastname: Mora
mesh_terms: D000116:Acetylgalactosamine / Q000097:blood*; D000117:Acetylglucosamine / Q000097:blood*; D000209:Acute-Phase Proteins / Q000032:analysis; D000368:Aged; D015415:Biomarkers; D001798:Blood Proteins / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000401:mortality; D002423:Cause of Death; D005260:Female; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000097:blood* / Q000737:chemistry; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007249:Inflammation / Q000097:blood; D053208:Kaplan-Meier Estimate; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009369:Neoplasms / Q000401:mortality; D019906:Nuclear Magnetic Resonance, Biomolecular; D011134:Polysaccharides / Q000097:blood*; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012306:Risk
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D001798:Blood Proteins; D006023:Glycoproteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011134:Polysaccharides; D002097:C-Reactive Protein; D000116:Acetylgalactosamine; D000117:Acetylglucosamine
keywords: cardiovascular diseases; glycoproteins; magnetic resonance spectroscopy; metabolomics; mortality; neoplasms; risk factors