{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T10:31:59Z","timestamp":1781173919351,"version":"3.54.1"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,3]]},"abstract":"\n Background<\/jats:title>\n \n Family history of coronary heart disease (\n CHD<\/jats:styled-content>\n ) as well as genetic predisposition to\n CHD<\/jats:styled-content>\n assessed by a genetic risk score (\n GRS<\/jats:styled-content>\n ) are predictors of\n CHD<\/jats:styled-content>\n risk. It is, however, uncertain to what extent these risk predictors are mediated by major metabolic pathways.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Total effects of self\u2010reported family history and a 50\u2010variant\n GRS<\/jats:styled-content>\n (\n GRS<\/jats:styled-content>\n 50), as well as effects mediated by apolipoprotein B and A\u2010I (apoB, apoA\u2010I), blood pressure, and diabetes mellitus, on incidence of\n CHD<\/jats:styled-content>\n were estimated in 23\u00a0595 participants of the Malm\u00f6 Diet and Cancer study (a prospective, population\u2010based study). During a median follow\u2010up of 14.4\u00a0years, 2213 participants experienced a first\n CHD<\/jats:styled-content>\n event. Family history of\n CHD<\/jats:styled-content>\n and\n GRS<\/jats:styled-content>\n 50 (highest versus other quintiles) were associated with incident\n CHD<\/jats:styled-content>\n , with hazard ratios of 1.52 (95%\n CI<\/jats:styled-content>\n : 1.39\u20131.65) and 1.53 (95%\n CI<\/jats:styled-content>\n : 1.39\u20131.68), respectively, after adjusting for age, sex, and smoking status. Small proportions of the family history effect were mediated by metabolic risk factors: 8.3% (95%\n CI<\/jats:styled-content>\n : 5.8\u201311.7%) by the apoB pathway, 1.7% (95%\n CI<\/jats:styled-content>\n : 0.2\u20133.4%) by apoA\u2010I, 8.5% (95%\n CI<\/jats:styled-content>\n : 5.9\u201312.0%) by blood pressure, and 1.5% (95%\n CI<\/jats:styled-content>\n : \u22120.8% to 3.8%) by diabetes mellitus. Similarly, small proportions of\n GRS<\/jats:styled-content>\n 50 were mediated: 8.1% (95%\n CI<\/jats:styled-content>\n : 5.5\u201311.8%) by apoB, 1.2% (95%\n CI<\/jats:styled-content>\n : 0.5\u20133.0%) by apoA\u2010I, 4.2% (95%\n CI<\/jats:styled-content>\n : 1.3\u20137.5%) by blood pressure, and \u22120.9% (95%\n CI<\/jats:styled-content>\n : \u22123.7% to 1.6%) by diabetes mellitus.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n A fraction of the\n CHD<\/jats:styled-content>\n risk associated with family history or with\n GRS<\/jats:styled-content>\n 50 is mediated through elevated blood lipids and hypertension, but not through diabetes mellitus. However, a major part (\u226580%) of the genetic effect operates independently of established metabolic risk factor pathways.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.116.005254","type":"journal-article","created":{"date-parts":[[2017,3,21]],"date-time":"2017-03-21T00:10:37Z","timestamp":1490055037000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Metabolic Mediators of the Effects of Family History and Genetic Risk Score on Coronary Heart Disease\u2014Findings From the Malm\u00f6 Diet and Cancer Study"],"prefix":"10.1161","volume":"6","author":[{"given":"Josef","family":"Fritz","sequence":"first","affiliation":[{"name":"Department of Medical Statistics, Informatics and Health Economics Medical University of Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dov","family":"Shiffman","sequence":"additional","affiliation":[{"name":"Quest Diagnostics San Juan Capistrano CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olle","family":"Melander","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund University Malm\u00f6 Sweden"},{"name":"Department of Internal Medicine Sk\u00e5ne University Hospital Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayato","family":"Tada","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Internal Medicine Kanazawa University Graduate School of Medicine Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanno","family":"Ulmer","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, Informatics and Health Economics Medical University of Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/hc2901.093115"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs475"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2014.11.017"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61267-6"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.113.301218"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61730-X"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.001"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.69.6.1065"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(84)80408-8"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a114223"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(91)90163-F"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0895-4356(95)00581-1"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.291.18.2204"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr225"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2480"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwr525"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwt270"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.1993.tb00647.x"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-009-9404-1"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.153981"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv462"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2458-11-450"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e31821c680c"},{"key":"e_1_3_1_25_2","unstructured":"Pearl J. 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