{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:05:52Z","timestamp":1792551952669,"version":"4.5.0"},"reference-count":82,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,8,21]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Osteoprotegerin is a cytokine involved in bone metabolism as well as vascular calcification and atherogenesis. Although circulating osteoprotegerin levels are robustly associated with incident cardiovascular disease (\n              <jats:styled-content style=\"fixed-case\">CVD<\/jats:styled-content>\n              ) in the general population, its relevance as a biomarker among populations at high\n              <jats:styled-content style=\"fixed-case\">CVD<\/jats:styled-content>\n              risk is less clear.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Three independent reviewers systematically searched PubMed,\n              <jats:styled-content style=\"fixed-case\">EMBASE<\/jats:styled-content>\n              , and Web of Science to identify prospective studies that had recruited participants on the basis of having conditions related to high\n              <jats:styled-content style=\"fixed-case\">CVD<\/jats:styled-content>\n              risk. A total of 19 studies were eligible for inclusion, reporting on 27\u00a0450 patients with diabetes mellitus (2 studies), kidney disease (7 studies), preexisting heart disease (5 studies), or recent acute coronary syndromes (5 studies) at baseline. Over a mean follow\u2010up of 4.2\u00a0years, 4066\n              <jats:styled-content style=\"fixed-case\">CVD<\/jats:styled-content>\n              events were recorded. In a random\u2010effects meta\u2010analysis, the pooled risk ratio for\n              <jats:styled-content style=\"fixed-case\">CVD<\/jats:styled-content>\n              events comparing people in the top versus the bottom tertile of osteoprotegerin concentration was 1.30 (95% confidence interval, 1.12\u20131.50;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001; I\n              <jats:sup>2<\/jats:sup>\n              =68.3%). There was evidence for presence of publication bias (\n              <jats:italic>P<\/jats:italic>\n              value from Egger's test=0.013). Correction for publication bias using the trim\u2010and\u2010fill method reduced the risk ratio to 1.21 (95% confidence interval, 1.03\u20131.42;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). The risk ratios did not vary significantly by population type, geographical region, statistical adjustment, sample or assay type, age, sex, or length of follow\u2010up.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In populations at high\n              <jats:styled-content style=\"fixed-case\">CVD<\/jats:styled-content>\n              risk, elevated circulating osteoprotegerin levels are associated with a higher risk for future\n              <jats:styled-content style=\"fixed-case\">CVD<\/jats:styled-content>\n              events. The magnitude of association appears weaker than in the general population.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.118.009012","type":"journal-article","created":{"date-parts":[[2018,9,14]],"date-time":"2018-09-14T20:16:46Z","timestamp":1536956206000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["Osteoprotegerin and Cardiovascular Events in High\u2010Risk Populations: Meta\u2010Analysis of 19 Prospective Studies Involving 27\u00a0450 Participants"],"prefix":"10.1161","volume":"7","author":[{"given":"Lena","family":"Tschiderer","sequence":"first","affiliation":[{"name":"Department of Neurology Medical University of Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Klingenschmid","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajini","family":"Nagrani","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann","family":"Willeit","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jari A.","family":"Laukkanen","sequence":"additional","affiliation":[{"name":"Institute of Public Health and Clinical Nutrition University of Eastern Finland Kuopio Finland"},{"name":"Central Finland Central Hospital Jyv\u00e4skyl\u00e4 Finland"},{"name":"Faculty of Sport and Health Sciences University of Jyv\u00e4skyl\u00e4 Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Schett","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 3 University of Erlangen\u2010Nuremberg Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kiechl","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Willeit","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Innsbruck Austria"},{"name":"Department of Public Health and Primary Care University of Cambridge United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80209-3"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81569-X"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.5.997"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.23.14363"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01658"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1586\/14779072.4.6.801"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031432"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/hq1201.100229"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000133194.94939.42"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2009.07.001"},{"key":"e_1_3_1_12_2","first-page":"4574","article-title":"RANK\/RANKL\/OPG pathway: genetic association with history of ischemic stroke in Italian population","volume":"20","author":"Biscetti F","year":"2016","unstructured":"Biscetti F, Giovannini S, Straface G, Bertucci F, Angelini F, Porreca C, Landolfi R, Flex A. 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