Very Low Levels of Atherogenic Lipoproteins and the Risk for Cardiovascular Events: A Meta-Analysis of Statin Trials
Identifieur interne : 003F43 ( Main/Merge ); précédent : 003F42; suivant : 003F44Very Low Levels of Atherogenic Lipoproteins and the Risk for Cardiovascular Events: A Meta-Analysis of Statin Trials
Auteurs : S. Matthijs Boekholdt [Pays-Bas] ; G. Kees Hovingh [Pays-Bas] ; Samia Mora [États-Unis] ; Benoit J. Arsenault [Pays-Bas] ; Pierre Amarenco [France] ; Terje R. Pedersen [Norvège] ; John C. Larosa [États-Unis] ; David D. Waters [États-Unis] ; David A. Demicco [États-Unis] ; R. John Simes [Australie] ; Antony C. Keech [Australie] ; David Colquhoun [Australie] ; Graham A. Hitman [Royaume-Uni] ; D. John Betteridge [Royaume-Uni] ; Michael B. Clearfield [États-Unis] ; John R. Downs [États-Unis] ; Helen M. Colhoun [Royaume-Uni] ; Antonio M. Jr Gotto [États-Unis] ; Paul M. Ridker [États-Unis] ; Scott M. Grundy [États-Unis] ; John J. P. Kastelein [Pays-Bas]Source :
- Journal of the American College of Cardiology [ 0735-1097 ] ; 2014.
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Abstract
BACKGROUND Levels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease risk is not well-documented. OBJECTIVES The aim of this meta-analysis was to evaluate: 1) the interindividual variability of reductions in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), or apolipoprotein B (apoB) levels achieved with statin therapy; 2) the proportion of patients not reaching guideline-recommended lipid levels on high-dose statin therapy; and 3) the association between very low levels of atherogenic lipoproteins achieved with statin therapy and cardiovascular disease risk. METHODS This meta-analysis used individual patient data from 8 randomized controlled statin trials, in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. RESULTS Among 38,153 patients allocated to statin therapy, a total of 6,286 major cardiovascular events occurred in 5,387 study participants during follow-up. There was large interindividual variability in the reductions of LDL-C, non-HDL-C, and apoB achieved with a fixed statin dose. More than 40% of trial participants assigned to high-dose statin therapy did not reach an LDL-C target <70 mg/dl. Compared with patients who achieved an LDL-C >175 mg/dl, those who reached an LDL-C 75 to <100 mg/dl, 50 to <75 mg/dl, and <50 mg/dl had adjusted hazard ratios for major cardiovascular events of 0.56 (95% confidence interval [CI]: 0.46 to 0.67), 0.51 (95% CI: 0.42 to 0.62), and 0.44 (95% CI: 0.35 to 0.55), respectively. Similar associations were observed for non-HDL-C and apoB. CONCLUSIONS The reductions of LDL-C, non-HDL-C, and apoB levels achieved with statin therapy displayed large interindividual variation. Among trial participants treated with high-dose statin therapy, >40% did not reach an LDL-C target <70 mg/dl. Patients who achieve very low LDL-C levels have a lower risk for major cardiovascular events than do those achieving moderately low levels.
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<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>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Very Low Levels of Atherogenic Lipoproteins and the Risk for Cardiovascular Events: A Meta-Analysis of Statin Trials</title>
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<author><name sortKey="Simes, R John" sort="Simes, R John" uniqKey="Simes R" first="R. John" last="Simes">R. John Simes</name>
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<author><name sortKey="Keech, Antony C" sort="Keech, Antony C" uniqKey="Keech A" first="Antony C." last="Keech">Antony C. Keech</name>
<affiliation wicri:level="4"><inist:fA14 i1="09"><s1>NHMRC Clinical Trials Centre, University of Sydney</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
<settlement type="city">Sydney</settlement>
</placeName>
<orgName type="university">Université de Sydney</orgName>
</affiliation>
</author>
<author><name sortKey="Colquhoun, David" sort="Colquhoun, David" uniqKey="Colquhoun D" first="David" last="Colquhoun">David Colquhoun</name>
<affiliation wicri:level="1"><inist:fA14 i1="10"><s1>The Wesley Hospital</s1>
<s2>Brisbane</s2>
<s3>AUS</s3>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>The Wesley Hospital</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hitman, Graham A" sort="Hitman, Graham A" uniqKey="Hitman G" first="Graham A." last="Hitman">Graham A. Hitman</name>
<affiliation wicri:level="4"><inist:fA14 i1="11"><s1>Centre for Diabetes, Barts and The London School of Medicine and Dentistry, Queen Mary University of London</s1>
<s2>London</s2>
<s3>GBR</s3>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
<settlement type="city">Londres</settlement>
</placeName>
<orgName type="university">Université de Londres</orgName>
</affiliation>
</author>
<author><name sortKey="Betteridge, D John" sort="Betteridge, D John" uniqKey="Betteridge D" first="D. John" last="Betteridge">D. John Betteridge</name>
<affiliation wicri:level="3"><inist:fA14 i1="12"><s1>Department of Endocrinology and Diabetes, University College Hospital</s1>
<s2>London</s2>
<s3>GBR</s3>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Clearfield, Michael B" sort="Clearfield, Michael B" uniqKey="Clearfield M" first="Michael B." last="Clearfield">Michael B. Clearfield</name>
<affiliation wicri:level="2"><inist:fA14 i1="13"><s1>Touro University</s1>
<s2>Mare Island, California</s2>
<s3>USA</s3>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Downs, John R" sort="Downs, John R" uniqKey="Downs J" first="John R." last="Downs">John R. Downs</name>
<affiliation wicri:level="2"><inist:fA14 i1="14"><s1>Department of Medicine, University of Texas Health Science Center</s1>
<s2>San Antonio, Texas</s2>
<s3>USA</s3>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><inist:fA14 i1="15"><s1>VERDICT, South Texas Veterans Health Care System</s1>
<s2>San Antonio, Texas</s2>
<s3>USA</s3>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Colhoun, Helen M" sort="Colhoun, Helen M" uniqKey="Colhoun H" first="Helen M." last="Colhoun">Helen M. Colhoun</name>
<affiliation wicri:level="1"><inist:fA14 i1="16"><s1>Medical Research Institute, University of Dundee</s1>
<s2>Dundee</s2>
<s3>GBR</s3>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<wicri:noRegion>Dundee</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gotto, Antonio M Jr" sort="Gotto, Antonio M Jr" uniqKey="Gotto A" first="Antonio M. Jr" last="Gotto">Antonio M. Jr Gotto</name>
<affiliation wicri:level="2"><inist:fA14 i1="17"><s1>Weill Cornell Medical College</s1>
<s2>New York, New York</s2>
<s3>USA</s3>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ridker, Paul M" sort="Ridker, Paul M" uniqKey="Ridker P" first="Paul M." last="Ridker">Paul M. Ridker</name>
<affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital</s1>
<s2>Boston, Massachusetts</s2>
<s3>USA</s3>
<sZ>3 aut.</sZ>
<sZ>19 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Grundy, Scott M" sort="Grundy, Scott M" uniqKey="Grundy S" first="Scott M." last="Grundy">Scott M. Grundy</name>
<affiliation wicri:level="2"><inist:fA14 i1="18"><s1>Center for Human Nutrition, Southwestern Medical Center, University of Texas</s1>
<s2>Dallas, Texas</s2>
<s3>USA</s3>
<sZ>20 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
</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="3"><inist:fA14 i1="02"><s1>Department of Vascular Medicine, Academic Medical Center</s1>
<s2>Amsterdam</s2>
<s3>NLD</s3>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>21 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<placeName><settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Journal of the American College of Cardiology</title>
<title level="j" type="abbreviated">J. Am. Coll. Cardiol.</title>
<idno type="ISSN">0735-1097</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Journal of the American College of Cardiology</title>
<title level="j" type="abbreviated">J. Am. Coll. Cardiol.</title>
<idno type="ISSN">0735-1097</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antilipemic agent</term>
<term>Cardiology</term>
<term>Cardiovascular disease</term>
<term>Circulatory system</term>
<term>Clinical trial</term>
<term>Level</term>
<term>Lipoprotein</term>
<term>Low</term>
<term>Metaanalysis</term>
<term>Risk</term>
<term>Risk factor</term>
<term>Statin derivative</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Faible</term>
<term>Niveau</term>
<term>Lipoprotéine</term>
<term>Facteur risque</term>
<term>Risque</term>
<term>Pathologie de l'appareil circulatoire</term>
<term>Métaanalyse</term>
<term>Dérivé de la statine</term>
<term>Essai clinique</term>
<term>Appareil circulatoire</term>
<term>Cardiologie</term>
<term>Hypolipémiant</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">BACKGROUND Levels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease risk is not well-documented. OBJECTIVES The aim of this meta-analysis was to evaluate: 1) the interindividual variability of reductions in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), or apolipoprotein B (apoB) levels achieved with statin therapy; 2) the proportion of patients not reaching guideline-recommended lipid levels on high-dose statin therapy; and 3) the association between very low levels of atherogenic lipoproteins achieved with statin therapy and cardiovascular disease risk. METHODS This meta-analysis used individual patient data from 8 randomized controlled statin trials, in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. RESULTS Among 38,153 patients allocated to statin therapy, a total of 6,286 major cardiovascular events occurred in 5,387 study participants during follow-up. There was large interindividual variability in the reductions of LDL-C, non-HDL-C, and apoB achieved with a fixed statin dose. More than 40% of trial participants assigned to high-dose statin therapy did not reach an LDL-C target <70 mg/dl. Compared with patients who achieved an LDL-C >175 mg/dl, those who reached an LDL-C 75 to <100 mg/dl, 50 to <75 mg/dl, and <50 mg/dl had adjusted hazard ratios for major cardiovascular events of 0.56 (95% confidence interval [CI]: 0.46 to 0.67), 0.51 (95% CI: 0.42 to 0.62), and 0.44 (95% CI: 0.35 to 0.55), respectively. Similar associations were observed for non-HDL-C and apoB. CONCLUSIONS The reductions of LDL-C, non-HDL-C, and apoB levels achieved with statin therapy displayed large interindividual variation. Among trial participants treated with high-dose statin therapy, >40% did not reach an LDL-C target <70 mg/dl. Patients who achieve very low LDL-C levels have a lower risk for major cardiovascular events than do those achieving moderately low levels.</div>
</front>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>France</li>
<li>Norvège</li>
<li>Pays-Bas</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region><li>Angleterre</li>
<li>Californie</li>
<li>Grand Londres</li>
<li>Hollande-Septentrionale</li>
<li>Massachusetts</li>
<li>Nouvelle-Galles du Sud</li>
<li>Texas</li>
<li>État de New York</li>
<li>Île-de-France</li>
<li>Østlandet</li>
</region>
<settlement><li>Amsterdam</li>
<li>Londres</li>
<li>Oslo</li>
<li>Paris</li>
<li>Sydney</li>
</settlement>
<orgName><li>Université de Londres</li>
<li>Université de Sydney</li>
</orgName>
</list>
<tree><country name="Pays-Bas"><region name="Hollande-Septentrionale"><name sortKey="Boekholdt, S Matthijs" sort="Boekholdt, S Matthijs" uniqKey="Boekholdt S" first="S. Matthijs" last="Boekholdt">S. Matthijs Boekholdt</name>
</region>
<name sortKey="Arsenault, Benoit J" sort="Arsenault, Benoit J" uniqKey="Arsenault B" first="Benoit J." last="Arsenault">Benoit J. Arsenault</name>
<name sortKey="Hovingh, G Kees" sort="Hovingh, G Kees" uniqKey="Hovingh G" first="G. Kees" last="Hovingh">G. Kees Hovingh</name>
<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>
</country>
<country name="États-Unis"><region name="Massachusetts"><name sortKey="Mora, Samia" sort="Mora, Samia" uniqKey="Mora S" first="Samia" last="Mora">Samia Mora</name>
</region>
<name sortKey="Clearfield, Michael B" sort="Clearfield, Michael B" uniqKey="Clearfield M" first="Michael B." last="Clearfield">Michael B. Clearfield</name>
<name sortKey="Demicco, David A" sort="Demicco, David A" uniqKey="Demicco D" first="David A." last="Demicco">David A. Demicco</name>
<name sortKey="Downs, John R" sort="Downs, John R" uniqKey="Downs J" first="John R." last="Downs">John R. Downs</name>
<name sortKey="Downs, John R" sort="Downs, John R" uniqKey="Downs J" first="John R." last="Downs">John R. Downs</name>
<name sortKey="Gotto, Antonio M Jr" sort="Gotto, Antonio M Jr" uniqKey="Gotto A" first="Antonio M. Jr" last="Gotto">Antonio M. Jr Gotto</name>
<name sortKey="Grundy, Scott M" sort="Grundy, Scott M" uniqKey="Grundy S" first="Scott M." last="Grundy">Scott M. Grundy</name>
<name sortKey="Larosa, John C" sort="Larosa, John C" uniqKey="Larosa J" first="John C." last="Larosa">John C. Larosa</name>
<name sortKey="Ridker, Paul M" sort="Ridker, Paul M" uniqKey="Ridker P" first="Paul M." last="Ridker">Paul M. Ridker</name>
<name sortKey="Waters, David D" sort="Waters, David D" uniqKey="Waters D" first="David D." last="Waters">David D. Waters</name>
</country>
<country name="France"><region name="Île-de-France"><name sortKey="Amarenco, Pierre" sort="Amarenco, Pierre" uniqKey="Amarenco P" first="Pierre" last="Amarenco">Pierre Amarenco</name>
</region>
</country>
<country name="Norvège"><region name="Østlandet"><name sortKey="Pedersen, Terje R" sort="Pedersen, Terje R" uniqKey="Pedersen T" first="Terje R." last="Pedersen">Terje R. Pedersen</name>
</region>
</country>
<country name="Australie"><region name="Nouvelle-Galles du Sud"><name sortKey="Simes, R John" sort="Simes, R John" uniqKey="Simes R" first="R. John" last="Simes">R. John Simes</name>
</region>
<name sortKey="Colquhoun, David" sort="Colquhoun, David" uniqKey="Colquhoun D" first="David" last="Colquhoun">David Colquhoun</name>
<name sortKey="Keech, Antony C" sort="Keech, Antony C" uniqKey="Keech A" first="Antony C." last="Keech">Antony C. Keech</name>
</country>
<country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Hitman, Graham A" sort="Hitman, Graham A" uniqKey="Hitman G" first="Graham A." last="Hitman">Graham A. Hitman</name>
</region>
<name sortKey="Betteridge, D John" sort="Betteridge, D John" uniqKey="Betteridge D" first="D. John" last="Betteridge">D. John Betteridge</name>
<name sortKey="Colhoun, Helen M" sort="Colhoun, Helen M" uniqKey="Colhoun H" first="Helen M." last="Colhoun">Helen M. Colhoun</name>
</country>
</tree>
</affiliations>
</record>
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