{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T01:43:49Z","timestamp":1792374229167,"version":"4.4.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Genome-wide association studies and preclinical studies demonstrated a role of sortilin in lipid metabolism, inflammation, and vascular calcification\u2014all 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).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              A cohort of community-dwelling men aged \u226550 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 \u226560 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\u20132.20;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). The third and fourth quartiles associated with 3.42-fold (95% confidence interval, 1.61\u20137.25;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.005) and 3.82-fold (95% confidence interval, 1.77\u20138.26;\n              <jats:italic>P<\/jats:italic>\n              &lt;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&gt;5) after adjustment for confounders (odds ratio, 1.43 per SD; 95% confidence interval, 1.10\u20131.85;\n              <jats:italic>P<\/jats:italic>\n              &lt;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.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.116.308932","type":"journal-article","created":{"date-parts":[[2017,3,10]],"date-time":"2017-03-10T02:10:30Z","timestamp":1489111830000},"page":"1005-1011","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":56,"title":["Serum Sortilin Associates With Aortic Calcification and Cardiovascular Risk in Men"],"prefix":"10.1161","volume":"37","author":[{"given":"Claudia","family":"Goettsch","sequence":"first","affiliation":[{"name":"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\u2019s Hospital, Harvard Medical School, Boston, MA; Boston VA Healthcare, Department of Cardiology, MA (C.J.O.); INSERM UMR 1033, University of Lyon, H\u00f4pital Edouard Herriot, Department of Rheumatology and Bone Pathology, France (R.C., P.S.); and Division of Preventive Medicine,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Iwata","sequence":"additional","affiliation":[{"name":"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\u2019s Hospital, Harvard Medical School, Boston, MA; Boston VA Healthcare, Department of Cardiology, MA (C.J.O.); INSERM UMR 1033, University of Lyon, H\u00f4pital Edouard Herriot, Department of Rheumatology and Bone Pathology, France (R.C., P.S.); and Division of Preventive Medicine,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Hutcheson","sequence":"additional","affiliation":[{"name":"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\u2019s Hospital, Harvard Medical School, Boston, MA; Boston VA Healthcare, Department of Cardiology, MA (C.J.O.); INSERM UMR 1033, University of Lyon, H\u00f4pital Edouard Herriot, Department of Rheumatology and Bone Pathology, France (R.C., P.S.); and Division of Preventive Medicine,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"O\u2019Donnell","sequence":"additional","affiliation":[{"name":"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\u2019s Hospital, Harvard Medical School, Boston, MA; Boston VA Healthcare, Department of Cardiology, MA (C.J.O.); INSERM UMR 1033, University of Lyon, H\u00f4pital Edouard Herriot, Department of Rheumatology and Bone Pathology, France (R.C., P.S.); and Division of Preventive Medicine,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Chapurlat","sequence":"additional","affiliation":[{"name":"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\u2019s Hospital, Harvard Medical School, Boston, MA; Boston VA Healthcare, Department of Cardiology, MA (C.J.O.); INSERM UMR 1033, University of Lyon, H\u00f4pital Edouard Herriot, Department of Rheumatology and Bone Pathology, France (R.C., P.S.); and Division of Preventive Medicine,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy R.","family":"Cook","sequence":"additional","affiliation":[{"name":"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\u2019s Hospital, Harvard Medical School, Boston, MA; Boston VA Healthcare, Department of Cardiology, MA (C.J.O.); INSERM UMR 1033, University of Lyon, H\u00f4pital Edouard Herriot, Department of Rheumatology and Bone Pathology, France (R.C., P.S.); and Division of Preventive Medicine,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Aikawa","sequence":"additional","affiliation":[{"name":"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\u2019s Hospital, Harvard Medical School, Boston, MA; Boston VA Healthcare, Department of Cardiology, MA (C.J.O.); INSERM UMR 1033, University of Lyon, H\u00f4pital Edouard Herriot, Department of Rheumatology and Bone Pathology, France (R.C., P.S.); and Division of Preventive Medicine,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel","family":"Szulc","sequence":"additional","affiliation":[{"name":"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\u2019s Hospital, Harvard Medical School, Boston, MA; Boston VA Healthcare, Department of Cardiology, MA (C.J.O.); INSERM UMR 1033, University of Lyon, H\u00f4pital Edouard Herriot, Department of Rheumatology and Bone Pathology, France (R.C., P.S.); and Division of Preventive Medicine,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Aikawa","sequence":"additional","affiliation":[{"name":"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\u2019s Hospital, Harvard Medical School, Boston, MA; Boston VA Healthcare, Department of Cardiology, MA (C.J.O.); INSERM UMR 1033, University of Lyon, H\u00f4pital Edouard Herriot, Department of Rheumatology and Bone Pathology, France (R.C., P.S.); and Division of Preventive Medicine,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.327"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt141"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2009.02.040"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.974899"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.13959"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09266"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.41.26273"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2005.04.004"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI76002"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.305811"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI80851"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2016.03.041"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.291.2.210"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.003625"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.488916"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2007.08.032"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.003144"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.11.1529"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.5551\/jat.33407"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.08.006"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63563"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.303268"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa072100"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.282535"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2015.09.004"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmat4519"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.732867"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8495"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12902-015-0034-1"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1996.03530440051036"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2010.195412"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/pr500659r"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1139\/apnm-2012-0231"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2015.167"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.116.308932","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T23:17:37Z","timestamp":1715555857000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.116.308932"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5]]},"references-count":34,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,5]]}},"alternative-id":["10.1161\/ATVBAHA.116.308932"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.116.308932","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5]]},"assertion":[{"value":"2016-12-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-02-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-03-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}