Small Dense Low-Density Lipoprotein-Cholesterol Concentrations Predict Risk for Coronary Heart Disease: The Atherosclerosis Risk in Communities (ARIC) Study
OBJECTIVE—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. APPROACH AND RESULTS—Plasma sdLD...
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| Veröffentlicht in: | Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2014-05, Vol.34 (5), p.1069-1077 |
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| creator | Hoogeveen, Ron C Gaubatz, John W Sun, Wensheng Dodge, Rhiannon C Crosby, Jacy R Jiang, Jennifer Couper, David Virani, Salim S Kathiresan, Sekar Boerwinkle, Eric Ballantyne, Christie M |
| description | OBJECTIVE—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.
APPROACH AND RESULTS—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 ≈11 years. Plasma sdLDL-C levels were strongly correlated with an atherogenic lipid profile and were higher in patients with diabetes mellitus than non–diabetes mellitus (49.6 versus 42.3 mg/dL; P |
| doi_str_mv | 10.1161/ATVBAHA.114.303284 |
| format | Article |
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APPROACH AND RESULTS—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 ≈11 years. Plasma sdLDL-C levels were strongly correlated with an atherogenic lipid profile and were higher in patients with diabetes mellitus than non–diabetes mellitus (49.6 versus 42.3 mg/dL; P<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, 1.21–1.88) 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, 1.04–2.49). 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, PCSK7, for which genetic variation was significantly associated with sdLDL-C and other lipid factors.
CONCLUSIONS—sdLDL-C was associated with incident CHD in ARIC study participants. The novel association of genetic variants in PCSK7 with sdLDL-C and other lipid traits may provide new insights into the role of this gene in lipid metabolism.</description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/ATVBAHA.114.303284</identifier><identifier>PMID: 24558110</identifier><language>eng</language><publisher>United States: American Heart Association, Inc</publisher><subject>Aged ; Atherosclerosis - blood ; Atherosclerosis - diagnosis ; Atherosclerosis - epidemiology ; Atherosclerosis - genetics ; Biomarkers - blood ; Cholesterol, LDL - blood ; Coronary Disease - blood ; Coronary Disease - diagnosis ; Coronary Disease - epidemiology ; Coronary Disease - genetics ; Female ; Genetic Predisposition to Disease ; Genetic Variation ; Genome-Wide Association Study ; Humans ; Incidence ; Linear Models ; Logistic Models ; Male ; Middle Aged ; Particle Size ; Phenotype ; Predictive Value of Tests ; Prevalence ; Prognosis ; Proportional Hazards Models ; Prospective Studies ; Risk Assessment ; Risk Factors ; Subtilisins - genetics ; Time Factors ; United States - epidemiology</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 2014-05, Vol.34 (5), p.1069-1077</ispartof><rights>2014 American Heart Association, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3504-306ed48aa49c2de146adef8cc1361ce1b950c0497c4bebcc74a914392a15da163</citedby><cites>FETCH-LOGICAL-c3504-306ed48aa49c2de146adef8cc1361ce1b950c0497c4bebcc74a914392a15da163</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24558110$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hoogeveen, Ron C</creatorcontrib><creatorcontrib>Gaubatz, John W</creatorcontrib><creatorcontrib>Sun, Wensheng</creatorcontrib><creatorcontrib>Dodge, Rhiannon C</creatorcontrib><creatorcontrib>Crosby, Jacy R</creatorcontrib><creatorcontrib>Jiang, Jennifer</creatorcontrib><creatorcontrib>Couper, David</creatorcontrib><creatorcontrib>Virani, Salim S</creatorcontrib><creatorcontrib>Kathiresan, Sekar</creatorcontrib><creatorcontrib>Boerwinkle, Eric</creatorcontrib><creatorcontrib>Ballantyne, Christie M</creatorcontrib><title>Small Dense Low-Density Lipoprotein-Cholesterol Concentrations Predict Risk for Coronary Heart Disease: The Atherosclerosis Risk in Communities (ARIC) Study</title><title>Arteriosclerosis, thrombosis, and vascular biology</title><addtitle>Arterioscler Thromb Vasc Biol</addtitle><description>OBJECTIVE—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.
APPROACH AND RESULTS—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 ≈11 years. Plasma sdLDL-C levels were strongly correlated with an atherogenic lipid profile and were higher in patients with diabetes mellitus than non–diabetes mellitus (49.6 versus 42.3 mg/dL; P<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, 1.21–1.88) 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, 1.04–2.49). 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, PCSK7, for which genetic variation was significantly associated with sdLDL-C and other lipid factors.
CONCLUSIONS—sdLDL-C was associated with incident CHD in ARIC study participants. The novel association of genetic variants in PCSK7 with sdLDL-C and other lipid traits may provide new insights into the role of this gene in lipid metabolism.</description><subject>Aged</subject><subject>Atherosclerosis - blood</subject><subject>Atherosclerosis - diagnosis</subject><subject>Atherosclerosis - epidemiology</subject><subject>Atherosclerosis - genetics</subject><subject>Biomarkers - blood</subject><subject>Cholesterol, LDL - blood</subject><subject>Coronary Disease - blood</subject><subject>Coronary Disease - diagnosis</subject><subject>Coronary Disease - epidemiology</subject><subject>Coronary Disease - genetics</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic Variation</subject><subject>Genome-Wide Association Study</subject><subject>Humans</subject><subject>Incidence</subject><subject>Linear Models</subject><subject>Logistic Models</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Particle Size</subject><subject>Phenotype</subject><subject>Predictive Value of Tests</subject><subject>Prevalence</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>Prospective Studies</subject><subject>Risk Assessment</subject><subject>Risk Factors</subject><subject>Subtilisins - genetics</subject><subject>Time Factors</subject><subject>United States - epidemiology</subject><issn>1079-5642</issn><issn>1524-4636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU1v1DAUtBCIlsIf4IB8LIcU27GdhFtIga20EqhduEZe561i6thb29Fq_ws_Fq-ycOTyPvRmRpo3CL2l5IZSST-0m5-f2lWbF35TkpLV_Bm6pILxgstSPs8zqZpCSM4u0KsYfxFCOGPkJbpgXIiaUnKJfj9Mylp8Cy4CXvtDcZpMOuK12ft98AmMK7rRW4gJgre4806DS0El413E3wMMRid8b-Ij3vmQ78E7FY54BSokfGsiqAgf8WYE3KYxa0RtT9XEhWRc5kzT7EwyEPF1e3_XvccPaR6Or9GLnbIR3pz7Ffrx5fOmWxXrb1_vunZd6FIQXpREwsBrpXij2QCUSzXArtaalpJqoNtGEE14U2m-ha3WFVcN5WXDFBWDorK8QteLbjb8NGen_WSiBmuVAz_Hngpa1VUlCMlQtkB1thAD7Pp9MFP221PSn1Lpz6nkhfdLKpn07qw_bycY_lH-xpABcgEcvM1vjo92PkDoR1A2jf9T_gPSuZvr</recordid><startdate>201405</startdate><enddate>201405</enddate><creator>Hoogeveen, Ron C</creator><creator>Gaubatz, John W</creator><creator>Sun, Wensheng</creator><creator>Dodge, Rhiannon C</creator><creator>Crosby, Jacy R</creator><creator>Jiang, Jennifer</creator><creator>Couper, David</creator><creator>Virani, Salim S</creator><creator>Kathiresan, Sekar</creator><creator>Boerwinkle, Eric</creator><creator>Ballantyne, Christie M</creator><general>American Heart Association, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201405</creationdate><title>Small Dense Low-Density Lipoprotein-Cholesterol Concentrations Predict Risk for Coronary Heart Disease: The Atherosclerosis Risk in Communities (ARIC) Study</title><author>Hoogeveen, Ron C ; Gaubatz, John W ; Sun, Wensheng ; Dodge, Rhiannon C ; Crosby, Jacy R ; Jiang, Jennifer ; Couper, David ; Virani, Salim S ; Kathiresan, Sekar ; Boerwinkle, Eric ; Ballantyne, Christie M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3504-306ed48aa49c2de146adef8cc1361ce1b950c0497c4bebcc74a914392a15da163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Aged</topic><topic>Atherosclerosis - blood</topic><topic>Atherosclerosis - diagnosis</topic><topic>Atherosclerosis - epidemiology</topic><topic>Atherosclerosis - genetics</topic><topic>Biomarkers - blood</topic><topic>Cholesterol, LDL - blood</topic><topic>Coronary Disease - blood</topic><topic>Coronary Disease - diagnosis</topic><topic>Coronary Disease - epidemiology</topic><topic>Coronary Disease - genetics</topic><topic>Female</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic Variation</topic><topic>Genome-Wide Association Study</topic><topic>Humans</topic><topic>Incidence</topic><topic>Linear Models</topic><topic>Logistic Models</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Particle Size</topic><topic>Phenotype</topic><topic>Predictive Value of Tests</topic><topic>Prevalence</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>Prospective Studies</topic><topic>Risk Assessment</topic><topic>Risk Factors</topic><topic>Subtilisins - genetics</topic><topic>Time Factors</topic><topic>United States - epidemiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hoogeveen, Ron C</creatorcontrib><creatorcontrib>Gaubatz, John W</creatorcontrib><creatorcontrib>Sun, Wensheng</creatorcontrib><creatorcontrib>Dodge, Rhiannon C</creatorcontrib><creatorcontrib>Crosby, Jacy R</creatorcontrib><creatorcontrib>Jiang, Jennifer</creatorcontrib><creatorcontrib>Couper, David</creatorcontrib><creatorcontrib>Virani, Salim S</creatorcontrib><creatorcontrib>Kathiresan, Sekar</creatorcontrib><creatorcontrib>Boerwinkle, Eric</creatorcontrib><creatorcontrib>Ballantyne, Christie M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hoogeveen, Ron C</au><au>Gaubatz, John W</au><au>Sun, Wensheng</au><au>Dodge, Rhiannon C</au><au>Crosby, Jacy R</au><au>Jiang, Jennifer</au><au>Couper, David</au><au>Virani, Salim S</au><au>Kathiresan, Sekar</au><au>Boerwinkle, Eric</au><au>Ballantyne, Christie M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Small Dense Low-Density Lipoprotein-Cholesterol Concentrations Predict Risk for Coronary Heart Disease: The Atherosclerosis Risk in Communities (ARIC) Study</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>2014-05</date><risdate>2014</risdate><volume>34</volume><issue>5</issue><spage>1069</spage><epage>1077</epage><pages>1069-1077</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><abstract>OBJECTIVE—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.
APPROACH AND RESULTS—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 ≈11 years. Plasma sdLDL-C levels were strongly correlated with an atherogenic lipid profile and were higher in patients with diabetes mellitus than non–diabetes mellitus (49.6 versus 42.3 mg/dL; P<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, 1.21–1.88) 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, 1.04–2.49). 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, PCSK7, for which genetic variation was significantly associated with sdLDL-C and other lipid factors.
CONCLUSIONS—sdLDL-C was associated with incident CHD in ARIC study participants. The novel association of genetic variants in PCSK7 with sdLDL-C and other lipid traits may provide new insights into the role of this gene in lipid metabolism.</abstract><cop>United States</cop><pub>American Heart Association, Inc</pub><pmid>24558110</pmid><doi>10.1161/ATVBAHA.114.303284</doi><tpages>9</tpages></addata></record> |
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| subjects | Aged Atherosclerosis - blood Atherosclerosis - diagnosis Atherosclerosis - epidemiology Atherosclerosis - genetics Biomarkers - blood Cholesterol, LDL - blood Coronary Disease - blood Coronary Disease - diagnosis Coronary Disease - epidemiology Coronary Disease - genetics Female Genetic Predisposition to Disease Genetic Variation Genome-Wide Association Study Humans Incidence Linear Models Logistic Models Male Middle Aged Particle Size Phenotype Predictive Value of Tests Prevalence Prognosis Proportional Hazards Models Prospective Studies Risk Assessment Risk Factors Subtilisins - genetics Time Factors United States - epidemiology |
| title | Small Dense Low-Density Lipoprotein-Cholesterol Concentrations Predict Risk for Coronary Heart Disease: The Atherosclerosis Risk in Communities (ARIC) Study |
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