{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:27:54Z","timestamp":1792272474477,"version":"4.4.0"},"reference-count":43,"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":[[2014,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective\u2014<\/jats:title>\n                    <jats:p>To investigate the relationship between plasma levels of small dense low-density lipoprotein-cholesterol (sdLDL-C) and risk for incident coronary heart disease (CHD) in a prospective study among Atherosclerosis Risk in Communities (ARIC) study participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results\u2014<\/jats:title>\n                    <jats:p>\n                      Plasma sdLDL-C was measured in 11 419 men and women of the biracial ARIC study using a newly developed homogeneous assay. A proportional hazards model was used to examine the relationship among sdLDL-C, vascular risk factors, and risk for CHD events (n=1158) for a period of \u224811 years. Plasma sdLDL-C levels were strongly correlated with an atherogenic lipid profile and were higher in patients with diabetes mellitus than non\u2013diabetes mellitus (49.6 versus 42.3 mg\/dL;\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.0001). In a model that included established risk factors, sdLDL-C was associated with incident CHD with a hazard ratio of 1.51 (95% confidence interval, 1.21\u20131.88) for the highest versus the lowest quartile, respectively. Even in individuals considered to be at low cardiovascular risk based on their LDL-C levels, sdLDL-C predicted risk for incident CHD (hazard ratio, 1.61; 95% confidence interval, 1.04\u20132.49). Genome-wide association analyses identified genetic variants in 8 loci associated with sdLDL-C levels. These loci were in or close to genes previously associated with risk for CHD. We discovered 1 novel locus,\n                      <jats:italic>PCSK7<\/jats:italic>\n                      , for which genetic variation was significantly associated with sdLDL-C and other lipid factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>\n                      sdLDL-C was associated with incident CHD in ARIC study participants. The novel association of genetic variants in\n                      <jats:italic>PCSK7<\/jats:italic>\n                      with sdLDL-C and other lipid traits may provide new insights into the role of this gene in lipid metabolism.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.114.303284","type":"journal-article","created":{"date-parts":[[2014,2,21]],"date-time":"2014-02-21T00:31:52Z","timestamp":1392942712000},"page":"1069-1077","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":471,"title":["Small Dense Low-Density Lipoprotein-Cholesterol Concentrations Predict Risk for Coronary Heart Disease"],"prefix":"10.1161","volume":"34","author":[{"given":"Ron C.","family":"Hoogeveen","sequence":"first","affiliation":[{"name":"From the Department of Medicine, Baylor College of Medicine and Methodist DeBakey Heart and Vascular Center, Houston, TX (R.C.H., J.W.G., W.S., J.J., S.S.V., C.M.B.); Human Genetics Center, University of Texas Health Science Center School of Public Health, Houston (R.C.D., J.R.C., E.B.); Department of Biostatistics, University of North Carolina at Chapel Hill (D.C.); Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.S.V.); Center for Human Genetic Research and Cardiovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Gaubatz","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Baylor College of Medicine and Methodist DeBakey Heart and Vascular Center, Houston, TX (R.C.H., J.W.G., W.S., J.J., S.S.V., C.M.B.); Human Genetics Center, University of Texas Health Science Center School of Public Health, Houston (R.C.D., J.R.C., E.B.); Department of Biostatistics, University of North Carolina at Chapel Hill (D.C.); Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.S.V.); Center for Human Genetic Research and Cardiovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wensheng","family":"Sun","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Baylor College of Medicine and Methodist DeBakey Heart and Vascular Center, Houston, TX (R.C.H., J.W.G., W.S., J.J., S.S.V., C.M.B.); Human Genetics Center, University of Texas Health Science Center School of Public Health, Houston (R.C.D., J.R.C., E.B.); Department of Biostatistics, University of North Carolina at Chapel Hill (D.C.); Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.S.V.); Center for Human Genetic Research and Cardiovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhiannon C.","family":"Dodge","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Baylor College of Medicine and Methodist DeBakey Heart and Vascular Center, Houston, TX (R.C.H., J.W.G., W.S., J.J., S.S.V., C.M.B.); Human Genetics Center, University of Texas Health Science Center School of Public Health, Houston (R.C.D., J.R.C., E.B.); Department of Biostatistics, University of North Carolina at Chapel Hill (D.C.); Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.S.V.); Center for Human Genetic Research and Cardiovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacy R.","family":"Crosby","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Baylor College of Medicine and Methodist DeBakey Heart and Vascular Center, Houston, TX (R.C.H., J.W.G., W.S., J.J., S.S.V., C.M.B.); Human Genetics Center, University of Texas Health Science Center School of Public Health, Houston (R.C.D., J.R.C., E.B.); Department of Biostatistics, University of North Carolina at Chapel Hill (D.C.); Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.S.V.); Center for Human Genetic Research and Cardiovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Jiang","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Baylor College of Medicine and Methodist DeBakey Heart and Vascular Center, Houston, TX (R.C.H., J.W.G., W.S., J.J., S.S.V., C.M.B.); Human Genetics Center, University of Texas Health Science Center School of Public Health, Houston (R.C.D., J.R.C., E.B.); Department of Biostatistics, University of North Carolina at Chapel Hill (D.C.); Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.S.V.); Center for Human Genetic Research and Cardiovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Couper","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Baylor College of Medicine and Methodist DeBakey Heart and Vascular Center, Houston, TX (R.C.H., J.W.G., W.S., J.J., S.S.V., C.M.B.); Human Genetics Center, University of Texas Health Science Center School of Public Health, Houston (R.C.D., J.R.C., E.B.); Department of Biostatistics, University of North Carolina at Chapel Hill (D.C.); Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.S.V.); Center for Human Genetic Research and Cardiovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salim S.","family":"Virani","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Baylor College of Medicine and Methodist DeBakey Heart and Vascular Center, Houston, TX (R.C.H., J.W.G., W.S., J.J., S.S.V., C.M.B.); Human Genetics Center, University of Texas Health Science Center School of Public Health, Houston (R.C.D., J.R.C., E.B.); Department of Biostatistics, University of North Carolina at Chapel Hill (D.C.); Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.S.V.); Center for Human Genetic Research and Cardiovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sekar","family":"Kathiresan","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Baylor College of Medicine and Methodist DeBakey Heart and Vascular Center, Houston, TX (R.C.H., J.W.G., W.S., J.J., S.S.V., C.M.B.); Human Genetics Center, University of Texas Health Science Center School of Public Health, Houston (R.C.D., J.R.C., E.B.); Department of Biostatistics, University of North Carolina at Chapel Hill (D.C.); Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.S.V.); Center for Human Genetic Research and Cardiovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Boerwinkle","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Baylor College of Medicine and Methodist DeBakey Heart and Vascular Center, Houston, TX (R.C.H., J.W.G., W.S., J.J., S.S.V., C.M.B.); Human Genetics Center, University of Texas Health Science Center School of Public Health, Houston (R.C.D., J.R.C., E.B.); Department of Biostatistics, University of North Carolina at Chapel Hill (D.C.); Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.S.V.); Center for Human Genetic Research and Cardiovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christie M.","family":"Ballantyne","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Baylor College of Medicine and Methodist DeBakey Heart and Vascular Center, Houston, TX (R.C.H., J.W.G., W.S., J.J., S.S.V., C.M.B.); Human Genetics Center, University of Texas Health Science Center School of Public Health, Houston (R.C.D., J.R.C., E.B.); Department of Biostatistics, University of North Carolina at Chapel Hill (D.C.); Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.S.V.); Center for Human Genetic Research and Cardiovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000133317.49796.0E"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr158"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)09327-3"},{"key":"e_1_3_5_5_2","article-title":"Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials.","author":"Cholesterol Treatment Trialists Collaboration","unstructured":"Cholesterol Treatment Trialists Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. The Lancet;376:1670\u20131681.","journal-title":"The Lancet;376:1670"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)38178-5"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9150(96)05842-X"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)40756-4"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)42610-0"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.9.2.176"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(98)00037-9"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.82.2.495"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cll.2006.07.006"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1994.tb04204.x"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2003.10.003"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2006.02.015"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1988.03410130125037"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.12.2.187"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)35731-X"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1996.03540110029028"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.95.1.69"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1996.03540110036029"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2010.149559"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.19.2486"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2011.02.001"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2009.137489"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000033222.75187.b9"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2006.05.007"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09270"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000730"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.113.302401"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0609-762c"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2480"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr372"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011690"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200318925"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa054013"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60312-2"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.291"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.115.6.1203"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-7060com"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.306407"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.217638"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.144279"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.114.303284","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T03:25:04Z","timestamp":1738812304000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.114.303284"}},"subtitle":["The Atherosclerosis Risk in Communities (ARIC) Study"],"short-title":[],"issued":{"date-parts":[[2014,5]]},"references-count":43,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2014,5]]}},"alternative-id":["10.1161\/ATVBAHA.114.303284"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.114.303284","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5]]},"assertion":[{"value":"2013-07-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-02-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-02-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}