Extreme Lipoprotein(a) Levels and Improved Cardiovascular Risk Prediction
Objectives The study tested whether extreme lipoprotein(a) levels and/or corresponding LPA risk genotypes improve myocardial infarction (MI) and coronary heart disease (CHD) risk prediction beyond conventional risk factors. Background Elevated lipoprotein(a) levels cause MI and CHD. Levels are prima...
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| Veröffentlicht in: | Journal of the American College of Cardiology 2013-03, Vol.61 (11), p.1146-1156 |
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| creator | Kamstrup, Pia R., MD, PhD Tybjærg-Hansen, Anne, MD, DMSc Nordestgaard, Børge G., MD, DMSc |
| description | Objectives The study tested whether extreme lipoprotein(a) levels and/or corresponding LPA risk genotypes improve myocardial infarction (MI) and coronary heart disease (CHD) risk prediction beyond conventional risk factors. Background Elevated lipoprotein(a) levels cause MI and CHD. Levels are primarily determined by variation in the LPA gene. Methods We followed 8,720 Danish participants in a general population study from 1991 to 1994 through 2011 without losses to follow-up. During this period, 730 and 1,683 first-time MI and CHD events occurred. Using predefined cutpoints for extreme lipoprotein(a) levels and/or corresponding LPA risk genotypes (kringle IV type 2 [KIV-2]) repeat polymorphism, rs3798220, and rs10455872 single nucleotide polymorphisms), we calculated net reclassification indices from |
| doi_str_mv | 10.1016/j.jacc.2012.12.023 |
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| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1317858281</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0735109713000430</els_id><sourcerecordid>3556891761</sourcerecordid><originalsourceid>FETCH-LOGICAL-c513t-d85c17522eb1b031b19b9dd3aff90219845e01c2aad5cf68e774d375508976233</originalsourceid><addsrcrecordid>eNp9kluLFDEQRoMo7rj6B3yQBhHWhx5TyaSTgAgyrDowoHh5DumkGtLblzHpHtx_b9oZXdgHIRAIp6pOPoqQ50DXQKF6065b69yaUWDrfCjjD8gKhFAlF1o-JCsquSiBanlBnqTUUkorBfoxuWCcS6E5XZHd9a8pYo_FPhzGQxwnDMOVfV3s8YhdKuzgi12f34_oi62NPoxHm9zc2Vh8Demm-BLRBzeFcXhKHjW2S_jsfF-SHx-uv28_lfvPH3fb9_vSCeBT6ZVwIAVjWENNOdSga-09t02jKQOtNgIpOGatF66pFEq58dlWUKVllcUvydWpb7b6OWOaTB-Sw66zA45zMsBBKqGYgoy-vIe24xyHbGeg2gjQUkiWKXaiXBxTitiYQwy9jbcGqFmCNq1ZgjZL0CYf-sfixbn1XPfo_5X8TTYDr85Azst2TbSDC-mOy6OhAp25tycux43HgNEkF3BwOdaIbjJ-DP_3eHev3HVhCHniDd5iuvuvSbnAfFtWYtkI4HkbNtnzN0oprh8</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1645197572</pqid></control><display><type>article</type><title>Extreme Lipoprotein(a) Levels and Improved Cardiovascular Risk Prediction</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Kamstrup, Pia R., MD, PhD ; Tybjærg-Hansen, Anne, MD, DMSc ; Nordestgaard, Børge G., MD, DMSc</creator><creatorcontrib>Kamstrup, Pia R., MD, PhD ; Tybjærg-Hansen, Anne, MD, DMSc ; Nordestgaard, Børge G., MD, DMSc</creatorcontrib><description>Objectives The study tested whether extreme lipoprotein(a) levels and/or corresponding LPA risk genotypes improve myocardial infarction (MI) and coronary heart disease (CHD) risk prediction beyond conventional risk factors. Background Elevated lipoprotein(a) levels cause MI and CHD. Levels are primarily determined by variation in the LPA gene. Methods We followed 8,720 Danish participants in a general population study from 1991 to 1994 through 2011 without losses to follow-up. During this period, 730 and 1,683 first-time MI and CHD events occurred. Using predefined cutpoints for extreme lipoprotein(a) levels and/or corresponding LPA risk genotypes (kringle IV type 2 [KIV-2]) repeat polymorphism, rs3798220, and rs10455872 single nucleotide polymorphisms), we calculated net reclassification indices from <10% to 10% to 19.9% to ≥20% absolute 10-year MI and CHD risk. Results For individuals with lipoprotein(a) levels ≥80th percentile (≥47 mg/dl), 23% (p < 0.001) of MI events and 12% (p < 0.001) of CHD events were reclassified correctly, while no events were reclassified incorrectly for either endpoint. As some incorrect reclassification of individuals with no events occurred, addition of lipoprotein(a) levels ≥80th percentile overall yielded net reclassification indices of +16% (95% confidence interval: 8% to 24%) and +3% (−1% to 8%) for MI and CHD, respectively. Corresponding net reclassification indices for number of KIV-2 repeats ≤21st percentile were +12% (5% to 19%) and +4% (0% to 8%), for rs3798220 carrier status +15% (−14% to 44%) and +10% (−10% to 30%), and for rs10455872 carrier status +16% (6% to 26%) and +2% (−1% to 6%). Considering only individuals at 10% to 19.9% absolute 10-year MI and CHD risk, addition of extreme lipoprotein(a) levels or corresponding LPA risk genotypes improved risk prediction even further. Conclusions Extreme lipoprotein(a) levels or corresponding LPA KIV-2/rs10455872 risk genotypes substantially improved MI and CHD risk prediction.</description><identifier>ISSN: 0735-1097</identifier><identifier>EISSN: 1558-3597</identifier><identifier>DOI: 10.1016/j.jacc.2012.12.023</identifier><identifier>PMID: 23375930</identifier><identifier>CODEN: JACCDI</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adult ; Aged ; Apolipoproteins ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology ; Cardiology. Vascular system ; Cardiovascular ; Cardiovascular disease ; Cholesterol ; Confidence intervals ; Coronary Disease - blood ; Coronary Disease - genetics ; coronary heart disease ; Diabetes ; Female ; Genotype ; Heart ; Hospitals ; Humans ; Internal Medicine ; lipoprotein(a) ; Lipoprotein(a) - blood ; Lipoprotein(a) - genetics ; Lipoproteins ; Male ; Medical sciences ; Middle Aged ; Myocardial Infarction - blood ; Myocardial Infarction - genetics ; Plasma ; Prognosis ; Risk Assessment - methods ; risk prediction ; Studies</subject><ispartof>Journal of the American College of Cardiology, 2013-03, Vol.61 (11), p.1146-1156</ispartof><rights>American College of Cardiology Foundation</rights><rights>2013 American College of Cardiology Foundation</rights><rights>2014 INIST-CNRS</rights><rights>Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Mar 19, 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c513t-d85c17522eb1b031b19b9dd3aff90219845e01c2aad5cf68e774d375508976233</citedby><cites>FETCH-LOGICAL-c513t-d85c17522eb1b031b19b9dd3aff90219845e01c2aad5cf68e774d375508976233</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0735109713000430$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27571619$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23375930$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kamstrup, Pia R., MD, PhD</creatorcontrib><creatorcontrib>Tybjærg-Hansen, Anne, MD, DMSc</creatorcontrib><creatorcontrib>Nordestgaard, Børge G., MD, DMSc</creatorcontrib><title>Extreme Lipoprotein(a) Levels and Improved Cardiovascular Risk Prediction</title><title>Journal of the American College of Cardiology</title><addtitle>J Am Coll Cardiol</addtitle><description>Objectives The study tested whether extreme lipoprotein(a) levels and/or corresponding LPA risk genotypes improve myocardial infarction (MI) and coronary heart disease (CHD) risk prediction beyond conventional risk factors. Background Elevated lipoprotein(a) levels cause MI and CHD. Levels are primarily determined by variation in the LPA gene. Methods We followed 8,720 Danish participants in a general population study from 1991 to 1994 through 2011 without losses to follow-up. During this period, 730 and 1,683 first-time MI and CHD events occurred. Using predefined cutpoints for extreme lipoprotein(a) levels and/or corresponding LPA risk genotypes (kringle IV type 2 [KIV-2]) repeat polymorphism, rs3798220, and rs10455872 single nucleotide polymorphisms), we calculated net reclassification indices from <10% to 10% to 19.9% to ≥20% absolute 10-year MI and CHD risk. Results For individuals with lipoprotein(a) levels ≥80th percentile (≥47 mg/dl), 23% (p < 0.001) of MI events and 12% (p < 0.001) of CHD events were reclassified correctly, while no events were reclassified incorrectly for either endpoint. As some incorrect reclassification of individuals with no events occurred, addition of lipoprotein(a) levels ≥80th percentile overall yielded net reclassification indices of +16% (95% confidence interval: 8% to 24%) and +3% (−1% to 8%) for MI and CHD, respectively. Corresponding net reclassification indices for number of KIV-2 repeats ≤21st percentile were +12% (5% to 19%) and +4% (0% to 8%), for rs3798220 carrier status +15% (−14% to 44%) and +10% (−10% to 30%), and for rs10455872 carrier status +16% (6% to 26%) and +2% (−1% to 6%). Considering only individuals at 10% to 19.9% absolute 10-year MI and CHD risk, addition of extreme lipoprotein(a) levels or corresponding LPA risk genotypes improved risk prediction even further. Conclusions Extreme lipoprotein(a) levels or corresponding LPA KIV-2/rs10455872 risk genotypes substantially improved MI and CHD risk prediction.</description><subject>Adult</subject><subject>Aged</subject><subject>Apolipoproteins</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology</subject><subject>Cardiology. Vascular system</subject><subject>Cardiovascular</subject><subject>Cardiovascular disease</subject><subject>Cholesterol</subject><subject>Confidence intervals</subject><subject>Coronary Disease - blood</subject><subject>Coronary Disease - genetics</subject><subject>coronary heart disease</subject><subject>Diabetes</subject><subject>Female</subject><subject>Genotype</subject><subject>Heart</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>lipoprotein(a)</subject><subject>Lipoprotein(a) - blood</subject><subject>Lipoprotein(a) - genetics</subject><subject>Lipoproteins</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Myocardial Infarction - blood</subject><subject>Myocardial Infarction - genetics</subject><subject>Plasma</subject><subject>Prognosis</subject><subject>Risk Assessment - methods</subject><subject>risk prediction</subject><subject>Studies</subject><issn>0735-1097</issn><issn>1558-3597</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kluLFDEQRoMo7rj6B3yQBhHWhx5TyaSTgAgyrDowoHh5DumkGtLblzHpHtx_b9oZXdgHIRAIp6pOPoqQ50DXQKF6065b69yaUWDrfCjjD8gKhFAlF1o-JCsquSiBanlBnqTUUkorBfoxuWCcS6E5XZHd9a8pYo_FPhzGQxwnDMOVfV3s8YhdKuzgi12f34_oi62NPoxHm9zc2Vh8Demm-BLRBzeFcXhKHjW2S_jsfF-SHx-uv28_lfvPH3fb9_vSCeBT6ZVwIAVjWENNOdSga-09t02jKQOtNgIpOGatF66pFEq58dlWUKVllcUvydWpb7b6OWOaTB-Sw66zA45zMsBBKqGYgoy-vIe24xyHbGeg2gjQUkiWKXaiXBxTitiYQwy9jbcGqFmCNq1ZgjZL0CYf-sfixbn1XPfo_5X8TTYDr85Azst2TbSDC-mOy6OhAp25tycux43HgNEkF3BwOdaIbjJ-DP_3eHev3HVhCHniDd5iuvuvSbnAfFtWYtkI4HkbNtnzN0oprh8</recordid><startdate>20130319</startdate><enddate>20130319</enddate><creator>Kamstrup, Pia R., MD, PhD</creator><creator>Tybjærg-Hansen, Anne, MD, DMSc</creator><creator>Nordestgaard, Børge G., MD, DMSc</creator><general>Elsevier Inc</general><general>Elsevier</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><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>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20130319</creationdate><title>Extreme Lipoprotein(a) Levels and Improved Cardiovascular Risk Prediction</title><author>Kamstrup, Pia R., MD, PhD ; Tybjærg-Hansen, Anne, MD, DMSc ; Nordestgaard, Børge G., MD, DMSc</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c513t-d85c17522eb1b031b19b9dd3aff90219845e01c2aad5cf68e774d375508976233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Apolipoproteins</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology</topic><topic>Cardiology. Vascular system</topic><topic>Cardiovascular</topic><topic>Cardiovascular disease</topic><topic>Cholesterol</topic><topic>Confidence intervals</topic><topic>Coronary Disease - blood</topic><topic>Coronary Disease - genetics</topic><topic>coronary heart disease</topic><topic>Diabetes</topic><topic>Female</topic><topic>Genotype</topic><topic>Heart</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>lipoprotein(a)</topic><topic>Lipoprotein(a) - blood</topic><topic>Lipoprotein(a) - genetics</topic><topic>Lipoproteins</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Myocardial Infarction - blood</topic><topic>Myocardial Infarction - genetics</topic><topic>Plasma</topic><topic>Prognosis</topic><topic>Risk Assessment - methods</topic><topic>risk prediction</topic><topic>Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kamstrup, Pia R., MD, PhD</creatorcontrib><creatorcontrib>Tybjærg-Hansen, Anne, MD, DMSc</creatorcontrib><creatorcontrib>Nordestgaard, Børge G., MD, DMSc</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of the American College of Cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kamstrup, Pia R., MD, PhD</au><au>Tybjærg-Hansen, Anne, MD, DMSc</au><au>Nordestgaard, Børge G., MD, DMSc</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Extreme Lipoprotein(a) Levels and Improved Cardiovascular Risk Prediction</atitle><jtitle>Journal of the American College of Cardiology</jtitle><addtitle>J Am Coll Cardiol</addtitle><date>2013-03-19</date><risdate>2013</risdate><volume>61</volume><issue>11</issue><spage>1146</spage><epage>1156</epage><pages>1146-1156</pages><issn>0735-1097</issn><eissn>1558-3597</eissn><coden>JACCDI</coden><abstract>Objectives The study tested whether extreme lipoprotein(a) levels and/or corresponding LPA risk genotypes improve myocardial infarction (MI) and coronary heart disease (CHD) risk prediction beyond conventional risk factors. Background Elevated lipoprotein(a) levels cause MI and CHD. Levels are primarily determined by variation in the LPA gene. Methods We followed 8,720 Danish participants in a general population study from 1991 to 1994 through 2011 without losses to follow-up. During this period, 730 and 1,683 first-time MI and CHD events occurred. Using predefined cutpoints for extreme lipoprotein(a) levels and/or corresponding LPA risk genotypes (kringle IV type 2 [KIV-2]) repeat polymorphism, rs3798220, and rs10455872 single nucleotide polymorphisms), we calculated net reclassification indices from <10% to 10% to 19.9% to ≥20% absolute 10-year MI and CHD risk. Results For individuals with lipoprotein(a) levels ≥80th percentile (≥47 mg/dl), 23% (p < 0.001) of MI events and 12% (p < 0.001) of CHD events were reclassified correctly, while no events were reclassified incorrectly for either endpoint. As some incorrect reclassification of individuals with no events occurred, addition of lipoprotein(a) levels ≥80th percentile overall yielded net reclassification indices of +16% (95% confidence interval: 8% to 24%) and +3% (−1% to 8%) for MI and CHD, respectively. Corresponding net reclassification indices for number of KIV-2 repeats ≤21st percentile were +12% (5% to 19%) and +4% (0% to 8%), for rs3798220 carrier status +15% (−14% to 44%) and +10% (−10% to 30%), and for rs10455872 carrier status +16% (6% to 26%) and +2% (−1% to 6%). Considering only individuals at 10% to 19.9% absolute 10-year MI and CHD risk, addition of extreme lipoprotein(a) levels or corresponding LPA risk genotypes improved risk prediction even further. Conclusions Extreme lipoprotein(a) levels or corresponding LPA KIV-2/rs10455872 risk genotypes substantially improved MI and CHD risk prediction.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>23375930</pmid><doi>10.1016/j.jacc.2012.12.023</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Apolipoproteins Atherosclerosis (general aspects, experimental research) Biological and medical sciences Blood and lymphatic vessels Cardiology Cardiology. Vascular system Cardiovascular Cardiovascular disease Cholesterol Confidence intervals Coronary Disease - blood Coronary Disease - genetics coronary heart disease Diabetes Female Genotype Heart Hospitals Humans Internal Medicine lipoprotein(a) Lipoprotein(a) - blood Lipoprotein(a) - genetics Lipoproteins Male Medical sciences Middle Aged Myocardial Infarction - blood Myocardial Infarction - genetics Plasma Prognosis Risk Assessment - methods risk prediction Studies |
| title | Extreme Lipoprotein(a) Levels and Improved Cardiovascular Risk Prediction |
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