title: Serum Sortilin Associates With Aortic Calcification and Cardiovascular Risk in Men.
abstract: Genome-wide association studies and preclinical studies demonstrated a role of sortilin in lipid metabolism, inflammation, and vascular calcification-all cardiovascular risk factors. We evaluated the association of serum sortilin levels with the risk of major adverse cerebrovascular and cardiovascular events (MACCE) and the severity of abdominal aortic calcification (AAC).
  
  
  
  A cohort of community-dwelling men aged ≥50 years (n=830) was assessed. At baseline, sortilin levels were measured by ELISA, and AAC was assessed on lateral spine scans obtained by dual-energy X-ray absorptiometry. Men aged ≥60 years (n=745) were followed up prospectively for the incidence of MACCE. During the median follow-up of 7.9 years, 76 MACCE occurred. The unadjusted incidence of MACCE across increasing sortilin quartiles was 8.0, 7.4, 19.8, and 20.3 per 1000 person-years. In multivariate-adjusted analysis, sortilin associated with increased risk of MACCE (hazard ratio, 1.70 per SD; 95% confidence interval, 1.30-2.20;P<0.001). The third and fourth quartiles associated with 3.42-fold (95% confidence interval, 1.61-7.25;P<0.005) and 3.82-fold (95% confidence interval, 1.77-8.26;P<0.001) higher risk of MACCE compared with the first quartile. High sortilin also predicted MACCE independent of traditional Framingham risk factors. Higher sortilin associated with higher odds of severe AAC (score>5) after adjustment for confounders (odds ratio, 1.43 per SD; 95% confidence interval, 1.10-1.85;P<0.01). The highest sortilin quartile associated with 2-fold higher odds of severe AAC (versus 3 lower quartiles combined). After adjustment for low-density lipoprotein cholesterol, the odds of severe AAC remained significant.
  
  
  
  In older men, higher serum sortilin levels associated with higher MACCE risk and severe AAC independently of relevant confounders, including C-reactive protein and low-density lipoprotein cholesterol. This finding, however, needs to be validated in other cohorts.
authors.affiliation: From the Center for Interdisciplinary Cardiovascular Sciences (C.G., H.I., J.D.H., M.A., E.A.) and Center for Excellence in Vascular Biology (M.A., E.A.), Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Boston VA Healthcare, Department of Cardiology, MA (C.J.O.); INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Department of Rheumatology and Bone Pathology, France (R.C., P.S.); and Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (N.R.C.).
authors.forename: Claudia
authors.initials: C
authors.lastname: Goettsch
authors.affiliation: From the Center for Interdisciplinary Cardiovascular Sciences (C.G., H.I., J.D.H., M.A., E.A.) and Center for Excellence in Vascular Biology (M.A., E.A.), Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Boston VA Healthcare, Department of Cardiology, MA (C.J.O.); INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Department of Rheumatology and Bone Pathology, France (R.C., P.S.); and Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (N.R.C.).
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwata
authors.affiliation: From the Center for Interdisciplinary Cardiovascular Sciences (C.G., H.I., J.D.H., M.A., E.A.) and Center for Excellence in Vascular Biology (M.A., E.A.), Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Boston VA Healthcare, Department of Cardiology, MA (C.J.O.); INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Department of Rheumatology and Bone Pathology, France (R.C., P.S.); and Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (N.R.C.).
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Hutcheson
authors.affiliation: From the Center for Interdisciplinary Cardiovascular Sciences (C.G., H.I., J.D.H., M.A., E.A.) and Center for Excellence in Vascular Biology (M.A., E.A.), Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Boston VA Healthcare, Department of Cardiology, MA (C.J.O.); INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Department of Rheumatology and Bone Pathology, France (R.C., P.S.); and Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (N.R.C.).
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.affiliation: From the Center for Interdisciplinary Cardiovascular Sciences (C.G., H.I., J.D.H., M.A., E.A.) and Center for Excellence in Vascular Biology (M.A., E.A.), Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Boston VA Healthcare, Department of Cardiology, MA (C.J.O.); INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Department of Rheumatology and Bone Pathology, France (R.C., P.S.); and Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (N.R.C.).
authors.forename: Roland
authors.initials: R
authors.lastname: Chapurlat
authors.affiliation: From the Center for Interdisciplinary Cardiovascular Sciences (C.G., H.I., J.D.H., M.A., E.A.) and Center for Excellence in Vascular Biology (M.A., E.A.), Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Boston VA Healthcare, Department of Cardiology, MA (C.J.O.); INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Department of Rheumatology and Bone Pathology, France (R.C., P.S.); and Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (N.R.C.).
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Cook
authors.affiliation: From the Center for Interdisciplinary Cardiovascular Sciences (C.G., H.I., J.D.H., M.A., E.A.) and Center for Excellence in Vascular Biology (M.A., E.A.), Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Boston VA Healthcare, Department of Cardiology, MA (C.J.O.); INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Department of Rheumatology and Bone Pathology, France (R.C., P.S.); and Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (N.R.C.).
authors.forename: Masanori
authors.initials: M
authors.lastname: Aikawa
authors.affiliation: From the Center for Interdisciplinary Cardiovascular Sciences (C.G., H.I., J.D.H., M.A., E.A.) and Center for Excellence in Vascular Biology (M.A., E.A.), Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Boston VA Healthcare, Department of Cardiology, MA (C.J.O.); INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Department of Rheumatology and Bone Pathology, France (R.C., P.S.); and Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (N.R.C.).
authors.forename: Pawel
authors.initials: P
authors.lastname: Szulc
authors.affiliation: From the Center for Interdisciplinary Cardiovascular Sciences (C.G., H.I., J.D.H., M.A., E.A.) and Center for Excellence in Vascular Biology (M.A., E.A.), Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Boston VA Healthcare, Department of Cardiology, MA (C.J.O.); INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Department of Rheumatology and Bone Pathology, France (R.C., P.S.); and Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (N.R.C.). eaikawa@partners.org.
authors.forename: Elena
authors.initials: E
authors.lastname: Aikawa
mesh_terms: D015502:Absorptiometry, Photon; D033942:Adaptor Proteins, Vesicular Transport / Q000097:blood*; D000368:Aged; D000369:Aged, 80 and over; D001012:Aorta, Abdominal / Q000000981:diagnostic imaging; D001018:Aortic Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002561:Cerebrovascular Disorders / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D016009:Chi-Square Distribution; D008078:Cholesterol, LDL / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005602:France / Q000453:epidemiology; D006331:Heart Diseases / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors; D013997:Time Factors; D015854:Up-Regulation; D061205:Vascular Calcification / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D015415:Biomarkers; D002097:C-Reactive Protein; D008078:Cholesterol, LDL; D000099183:Sortilin
keywords: cardiovascular calcification; cardiovascular disease; low-density lipoprotein; risk factors; sortilin