Association of Genetic Variants Related to CETP Inhibitors and Statins With Lipoprotein Levels and Cardiovascular Risk.
Identifieur interne : 000518 ( PubMed/Curation ); précédent : 000517; suivant : 000519Association of Genetic Variants Related to CETP Inhibitors and Statins With Lipoprotein Levels and Cardiovascular Risk.
Auteurs : Brian A. Ference [États-Unis] ; John J P. Kastelein [Pays-Bas] ; Henry N. Ginsberg [États-Unis] ; M John Chapman [France] ; Stephen J. Nicholls [Australie] ; Kausik K. Ray [Royaume-Uni] ; Chris J. Packard [Royaume-Uni] ; Ulrich Laufs [Allemagne] ; Robert D. Brook ; Clare Oliver-Williams [Royaume-Uni] ; Adam S. Butterworth [Royaume-Uni] ; John Danesh [Royaume-Uni] ; George Davey Smith [Royaume-Uni] ; Alberico L. Catapano [Italie] ; Marc S. Sabatine [États-Unis]Source :
- JAMA [ 1538-3598 ] ; 2017.
Descripteurs français
- KwdFr :
- Adulte d'âge moyen, Analyse de randomisation mendélienne, Anticholestérolémiants (usage thérapeutique), Apolipoprotéines B (sang), Cholestérol HDL (sang), Cholestérol LDL (sang), Facteurs de risque, Femelle, Humains, Hydroxymethylglutaryl-CoA reductases (génétique), Hypercholestérolémie (génétique), Hypercholestérolémie (sang), Hypercholestérolémie (traitement médicamenteux), Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase (usage thérapeutique), Maladies cardiovasculaires (), Maladies cardiovasculaires (génétique), Mâle, Protéines de transfert des esters de cholestérol (antagonistes et inhibiteurs), Protéines de transfert des esters de cholestérol (génétique), Variation génétique.
- MESH :
- antagonistes et inhibiteurs : Protéines de transfert des esters de cholestérol.
- génétique : Hydroxymethylglutaryl-CoA reductases, Hypercholestérolémie, Maladies cardiovasculaires, Protéines de transfert des esters de cholestérol.
- sang : Apolipoprotéines B, Cholestérol HDL, Cholestérol LDL, Hypercholestérolémie.
- traitement médicamenteux : Hypercholestérolémie.
- usage thérapeutique : Anticholestérolémiants, Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase.
- Adulte d'âge moyen, Analyse de randomisation mendélienne, Facteurs de risque, Femelle, Humains, Maladies cardiovasculaires, Mâle, Variation génétique.
English descriptors
- KwdEn :
- Anticholesteremic Agents (therapeutic use), Apolipoproteins B (blood), Cardiovascular Diseases (genetics), Cardiovascular Diseases (prevention & control), Cholesterol Ester Transfer Proteins (antagonists & inhibitors), Cholesterol Ester Transfer Proteins (genetics), Cholesterol, HDL (blood), Cholesterol, LDL (blood), Female, Genetic Variation, Humans, Hydroxymethylglutaryl CoA Reductases (genetics), Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use), Hypercholesterolemia (blood), Hypercholesterolemia (drug therapy), Hypercholesterolemia (genetics), Male, Mendelian Randomization Analysis, Middle Aged, Risk Factors.
- MESH :
- chemical , antagonists & inhibitors : Cholesterol Ester Transfer Proteins.
- chemical , blood : Apolipoproteins B, Cholesterol, HDL, Cholesterol, LDL.
- chemical , genetics : Cholesterol Ester Transfer Proteins, Hydroxymethylglutaryl CoA Reductases.
- chemical , therapeutic use : Anticholesteremic Agents, Hydroxymethylglutaryl-CoA Reductase Inhibitors.
- blood : Hypercholesterolemia.
- drug therapy : Hypercholesterolemia.
- genetics : Cardiovascular Diseases, Hypercholesterolemia.
- prevention & control : Cardiovascular Diseases.
- Female, Genetic Variation, Humans, Male, Mendelian Randomization Analysis, Middle Aged, Risk Factors.
Abstract
Some cholesteryl ester transfer protein (CETP) inhibitors lower low-density lipoprotein cholesterol (LDL-C) levels without reducing cardiovascular events, suggesting that the clinical benefit of lowering LDL-C may depend on how LDL-C is lowered.
DOI: 10.1001/jama.2017.11467
PubMed: 28846118
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Robert D. Brook<affiliation><nlm:affiliation>Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor.</nlm:affiliation><wicri:noCountry code="subField">Ann Arbor</wicri:noCountry></affiliation>Le document en format XML
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Ference</name><affiliation wicri:level="2"><nlm:affiliation>Division of Cardiovascular Medicine, Wayne State University School of Medicine, Detroit, Michigan.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Michigan</region></placeName><wicri:cityArea>Division of Cardiovascular Medicine, Wayne State University School of Medicine, Detroit</wicri:cityArea></affiliation></author><author><name sortKey="Kastelein, John J P" sort="Kastelein, John J P" uniqKey="Kastelein J" first="John J P" last="Kastelein">John J P. Kastelein</name><affiliation wicri:level="1"><nlm:affiliation>Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam</wicri:regionArea></affiliation></author><author><name sortKey="Ginsberg, Henry N" sort="Ginsberg, Henry N" uniqKey="Ginsberg H" first="Henry N" last="Ginsberg">Henry N. Ginsberg</name><affiliation wicri:level="2"><nlm:affiliation>Irving Institute for Clinical and Translational Research, Columbia University College of Physicians and Surgeons, New York, New York.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Irving Institute for Clinical and Translational Research, Columbia University College of Physicians and Surgeons, New York</wicri:cityArea></affiliation></author><author><name sortKey="Chapman, M John" sort="Chapman, M John" uniqKey="Chapman M" first="M John" last="Chapman">M John Chapman</name><affiliation wicri:level="1"><nlm:affiliation>National Institute for Health and Medical Research (INSERM), Pitie-Salpetriere University Hospital, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>National Institute for Health and Medical Research (INSERM), Pitie-Salpetriere University Hospital, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Nicholls, Stephen J" sort="Nicholls, Stephen J" uniqKey="Nicholls S" first="Stephen J" last="Nicholls">Stephen J. Nicholls</name><affiliation wicri:level="1"><nlm:affiliation>South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>South Australian Health and Medical Research Institute, University of Adelaide, Adelaide</wicri:regionArea></affiliation></author><author><name sortKey="Ray, Kausik K" sort="Ray, Kausik K" uniqKey="Ray K" first="Kausik K" last="Ray">Kausik K. Ray</name><affiliation wicri:level="1"><nlm:affiliation>Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London</wicri:regionArea></affiliation></author><author><name sortKey="Packard, Chris J" sort="Packard, Chris J" uniqKey="Packard C" first="Chris J" last="Packard">Chris J. Packard</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow</wicri:regionArea></affiliation></author><author><name sortKey="Laufs, Ulrich" sort="Laufs, Ulrich" uniqKey="Laufs U" first="Ulrich" last="Laufs">Ulrich Laufs</name><affiliation wicri:level="1"><nlm:affiliation>Department of Cardiology, University of Leipzig, Leipzig, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Cardiology, University of Leipzig, Leipzig</wicri:regionArea></affiliation></author><author><name sortKey="Brook, Robert D" sort="Brook, Robert D" uniqKey="Brook R" first="Robert D" last="Brook">Robert D. Brook</name><affiliation><nlm:affiliation>Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor.</nlm:affiliation><wicri:noCountry code="subField">Ann Arbor</wicri:noCountry></affiliation></author><author><name sortKey="Oliver Williams, Clare" sort="Oliver Williams, Clare" uniqKey="Oliver Williams C" first="Clare" last="Oliver-Williams">Clare Oliver-Williams</name><affiliation wicri:level="1"><nlm:affiliation>MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Butterworth, Adam S" sort="Butterworth, Adam S" uniqKey="Butterworth A" first="Adam S" last="Butterworth">Adam S. Butterworth</name><affiliation wicri:level="1"><nlm:affiliation>MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Danesh, John" sort="Danesh, John" uniqKey="Danesh J" first="John" last="Danesh">John Danesh</name><affiliation wicri:level="1"><nlm:affiliation>MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Smith, George Davey" sort="Smith, George Davey" uniqKey="Smith G" first="George Davey" last="Smith">George Davey Smith</name><affiliation wicri:level="1"><nlm:affiliation>MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>MRC Integrative Epidemiology Unit, University of Bristol, Bristol</wicri:regionArea></affiliation></author><author><name sortKey="Catapano, Alberico L" sort="Catapano, Alberico L" uniqKey="Catapano A" first="Alberico L" last="Catapano">Alberico L. Catapano</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pharmacological and Biomolecular Sciences, University of Milan and Multimedica IRCCS, Milano, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Pharmacological and Biomolecular Sciences, University of Milan and Multimedica IRCCS, Milano</wicri:regionArea></affiliation></author><author><name sortKey="Sabatine, Marc S" sort="Sabatine, Marc S" uniqKey="Sabatine M" first="Marc S" last="Sabatine">Marc S. Sabatine</name><affiliation wicri:level="2"><nlm:affiliation>Thrombolysis in Myocardial Infarction (TIMI) Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Thrombolysis in Myocardial Infarction (TIMI) Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston</wicri:cityArea></affiliation></author></analytic><series><title level="j">JAMA</title><idno type="eISSN">1538-3598</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Anticholesteremic Agents (therapeutic use)</term><term>Apolipoproteins B (blood)</term><term>Cardiovascular Diseases (genetics)</term><term>Cardiovascular Diseases (prevention & control)</term><term>Cholesterol Ester Transfer Proteins (antagonists & inhibitors)</term><term>Cholesterol Ester Transfer Proteins (genetics)</term><term>Cholesterol, HDL (blood)</term><term>Cholesterol, LDL (blood)</term><term>Female</term><term>Genetic Variation</term><term>Humans</term><term>Hydroxymethylglutaryl CoA Reductases (genetics)</term><term>Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)</term><term>Hypercholesterolemia (blood)</term><term>Hypercholesterolemia (drug therapy)</term><term>Hypercholesterolemia (genetics)</term><term>Male</term><term>Mendelian Randomization Analysis</term><term>Middle Aged</term><term>Risk Factors</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Analyse de randomisation mendélienne</term><term>Anticholestérolémiants (usage thérapeutique)</term><term>Apolipoprotéines B (sang)</term><term>Cholestérol HDL (sang)</term><term>Cholestérol LDL (sang)</term><term>Facteurs de risque</term><term>Femelle</term><term>Humains</term><term>Hydroxymethylglutaryl-CoA reductases (génétique)</term><term>Hypercholestérolémie (génétique)</term><term>Hypercholestérolémie (sang)</term><term>Hypercholestérolémie (traitement médicamenteux)</term><term>Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase (usage thérapeutique)</term><term>Maladies cardiovasculaires ()</term><term>Maladies cardiovasculaires (génétique)</term><term>Mâle</term><term>Protéines de transfert des esters de cholestérol (antagonistes et inhibiteurs)</term><term>Protéines de transfert des esters de cholestérol (génétique)</term><term>Variation génétique</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Cholesterol Ester Transfer Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Apolipoproteins B</term><term>Cholesterol, HDL</term><term>Cholesterol, LDL</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cholesterol Ester Transfer Proteins</term><term>Hydroxymethylglutaryl CoA Reductases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Anticholesteremic Agents</term><term>Hydroxymethylglutaryl-CoA Reductase Inhibitors</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Protéines de transfert des esters de cholestérol</term></keywords><keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Hypercholesterolemia</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Hypercholesterolemia</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Cardiovascular Diseases</term><term>Hypercholesterolemia</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Hydroxymethylglutaryl-CoA reductases</term><term>Hypercholestérolémie</term><term>Maladies cardiovasculaires</term><term>Protéines de transfert des esters de cholestérol</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Cardiovascular Diseases</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Apolipoprotéines B</term><term>Cholestérol HDL</term><term>Cholestérol LDL</term><term>Hypercholestérolémie</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Hypercholestérolémie</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Anticholestérolémiants</term><term>Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Female</term><term>Genetic Variation</term><term>Humans</term><term>Male</term><term>Mendelian Randomization Analysis</term><term>Middle Aged</term><term>Risk Factors</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Analyse de randomisation mendélienne</term><term>Facteurs de risque</term><term>Femelle</term><term>Humains</term><term>Maladies cardiovasculaires</term><term>Mâle</term><term>Variation génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Some cholesteryl ester transfer protein (CETP) inhibitors lower low-density lipoprotein cholesterol (LDL-C) levels without reducing cardiovascular events, suggesting that the clinical benefit of lowering LDL-C may depend on how LDL-C is lowered.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28846118</PMID><DateCreated><Year>2017</Year><Month>08</Month><Day>28</Day></DateCreated><DateCompleted><Year>2017</Year><Month>09</Month><Day>20</Day></DateCompleted><DateRevised><Year>2017</Year><Month>09</Month><Day>22</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1538-3598</ISSN><JournalIssue CitedMedium="Internet"><Volume>318</Volume><Issue>10</Issue><PubDate><Year>2017</Year><Month>09</Month><Day>12</Day></PubDate></JournalIssue><Title>JAMA</Title><ISOAbbreviation>JAMA</ISOAbbreviation></Journal><ArticleTitle>Association of Genetic Variants Related to CETP Inhibitors and Statins With Lipoprotein Levels and Cardiovascular Risk.</ArticleTitle><Pagination><MedlinePgn>947-956</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1001/jama.2017.11467</ELocationID><Abstract><AbstractText Label="Importance">Some cholesteryl ester transfer protein (CETP) inhibitors lower low-density lipoprotein cholesterol (LDL-C) levels without reducing cardiovascular events, suggesting that the clinical benefit of lowering LDL-C may depend on how LDL-C is lowered.</AbstractText><AbstractText Label="Objective">To estimate the association between changes in levels of LDL-C (and other lipoproteins) and the risk of cardiovascular events related to variants in the CETP gene, both alone and in combination with variants in the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) gene.</AbstractText><AbstractText Label="Design, Setting, and Participants">Mendelian randomization analyses evaluating the association between CETP and HMGCR scores, changes in lipid and lipoprotein levels, and the risk of cardiovascular events involving 102 837 participants from 14 cohort or case-control studies conducted in North America or the United Kingdom between 1948 and 2012. The associations with cardiovascular events were externally validated in 189 539 participants from 48 studies conducted between 2011 and 2015.</AbstractText><AbstractText Label="Exposures">Differences in mean high-density lipoprotein cholesterol (HDL-C), LDL-C, and apolipoprotein B (apoB) levels in participants with CETP scores at or above vs below the median.</AbstractText><AbstractText Label="Main Outcomes and Measures">Odds ratio (OR) for major cardiovascular events.</AbstractText><AbstractText Label="Results">The primary analysis included 102 837 participants (mean age, 59.9 years; 58% women) who experienced 13 821 major cardiovascular events. The validation analyses included 189 539 participants (mean age, 58.5 years; 39% women) with 62 240 cases of coronary heart disease (CHD). Considered alone, the CETP score was associated with higher levels of HDL-C, lower LDL-C, concordantly lower apoB, and a corresponding lower risk of major vascular events (OR, 0.946 [95% CI, 0.921-0.972]) that was similar in magnitude to the association between the HMGCR score and risk of major cardiovascular events per unit change in levels of LDL-C (and apoB). When combined with the HMGCR score, the CETP score was associated with the same reduction in LDL-C levels but an attenuated reduction in apoB levels and a corresponding attenuated nonsignificant risk of major cardiovascular events (OR, 0.985 [95% CI, 0.955-1.015]). In external validation analyses, a genetic score consisting of variants with naturally occurring discordance between levels of LDL-C and apoB was associated with a similar risk of CHD per unit change in apoB level (OR, 0.782 [95% CI, 0.720-0.845] vs 0.793 [95% CI, 0.774-0.812]; P = .79 for difference), but a significantly attenuated risk of CHD per unit change in LDL-C level (OR, 0.916 [95% CI, 0.890-0.943] vs 0.831 [95% CI, 0.816-0.847]; P < .001) compared with a genetic score associated with concordant changes in levels of LDL-C and apoB.</AbstractText><AbstractText Label="Conclusions and Relevance">Combined exposure to variants in the genes that encode the targets of CETP inhibitors and statins was associated with discordant reductions in LDL-C and apoB levels and a corresponding risk of cardiovascular events that was proportional to the attenuated reduction in apoB but significantly less than expected per unit change in LDL-C. The clinical benefit of lowering LDL-C levels may therefore depend on the corresponding reduction in apoB-containing lipoprotein particles.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ference</LastName><ForeName>Brian A</ForeName><Initials>BA</Initials><AffiliationInfo><Affiliation>Division of Cardiovascular Medicine, Wayne State University School of Medicine, Detroit, Michigan.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute for Advanced Studies, University of Bristol, Bristol, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kastelein</LastName><ForeName>John J P</ForeName><Initials>JJP</Initials><AffiliationInfo><Affiliation>Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ginsberg</LastName><ForeName>Henry N</ForeName><Initials>HN</Initials><AffiliationInfo><Affiliation>Irving Institute for Clinical and Translational Research, Columbia University College of Physicians and Surgeons, New York, New York.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chapman</LastName><ForeName>M John</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>National Institute for Health and Medical Research (INSERM), Pitie-Salpetriere University Hospital, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nicholls</LastName><ForeName>Stephen J</ForeName><Initials>SJ</Initials><AffiliationInfo><Affiliation>South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ray</LastName><ForeName>Kausik K</ForeName><Initials>KK</Initials><AffiliationInfo><Affiliation>Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Packard</LastName><ForeName>Chris J</ForeName><Initials>CJ</Initials><AffiliationInfo><Affiliation>Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Laufs</LastName><ForeName>Ulrich</ForeName><Initials>U</Initials><AffiliationInfo><Affiliation>Department of Cardiology, University of Leipzig, Leipzig, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brook</LastName><ForeName>Robert D</ForeName><Initials>RD</Initials><AffiliationInfo><Affiliation>Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Oliver-Williams</LastName><ForeName>Clare</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Butterworth</LastName><ForeName>Adam S</ForeName><Initials>AS</Initials><AffiliationInfo><Affiliation>MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Danesh</LastName><ForeName>John</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Wellcome Trust Sanger Institute, Hinxton, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Smith</LastName><ForeName>George Davey</ForeName><Initials>GD</Initials><AffiliationInfo><Affiliation>MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Catapano</LastName><ForeName>Alberico L</ForeName><Initials>AL</Initials><AffiliationInfo><Affiliation>Department of Pharmacological and Biomolecular Sciences, University of Milan and Multimedica IRCCS, Milano, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sabatine</LastName><ForeName>Marc S</ForeName><Initials>MS</Initials><AffiliationInfo><Affiliation>Thrombolysis in Myocardial Infarction (TIMI) Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D003160">Comparative Study</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>JAMA</MedlineTA><NlmUniqueID>7501160</NlmUniqueID><ISSNLinking>0098-7484</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000924">Anticholesteremic Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D001055">Apolipoproteins B</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C506642">CETP protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D053480">Cholesterol Ester Transfer Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D008076">Cholesterol, HDL</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D008078">Cholesterol, LDL</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019161">Hydroxymethylglutaryl-CoA Reductase Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.1.1.-</RegistryNumber><NameOfSubstance UI="C553220">HMGCR protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.1.1.-</RegistryNumber><NameOfSubstance UI="D006903">Hydroxymethylglutaryl CoA Reductases</NameOfSubstance></Chemical></ChemicalList><CitationSubset>AIM</CitationSubset><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="CommentIn"><RefSource>JAMA. 2017 Sep 12;318(10 ):915-917</RefSource><PMID Version="1">28846117</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D000924" MajorTopicYN="N">Anticholesteremic Agents</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001055" MajorTopicYN="N">Apolipoproteins B</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="Y">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002318" MajorTopicYN="N">Cardiovascular Diseases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000517" MajorTopicYN="N">prevention & control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053480" MajorTopicYN="N">Cholesterol Ester Transfer Proteins</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008076" MajorTopicYN="N">Cholesterol, HDL</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008078" MajorTopicYN="N">Cholesterol, LDL</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="Y">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014644" MajorTopicYN="Y">Genetic Variation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006903" MajorTopicYN="N">Hydroxymethylglutaryl CoA Reductases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019161" MajorTopicYN="N">Hydroxymethylglutaryl-CoA Reductase Inhibitors</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006937" MajorTopicYN="N">Hypercholesterolemia</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D057182" MajorTopicYN="N">Mendelian Randomization 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