Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia
Sitosterolemia is a recessively inherited disorder that results from mutations in either ABCG5 or G8 proteins, with hyperabsorption of dietary sterols and decreased hepatic excretion of plant sterols and cholesterol. As a consequence of markedly elevated plasma and tissue sitosterol and campesterol...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2004-03, Vol.109 (8), p.966-971 |
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| creator | SALEN, G VON BERGMANN, K LÜTJOHANN, D KWITEROVICH, P KANE, J PATEL, S. B MUSLINER, T STEIN, P MUSSER, B |
| description | Sitosterolemia is a recessively inherited disorder that results from mutations in either ABCG5 or G8 proteins, with hyperabsorption of dietary sterols and decreased hepatic excretion of plant sterols and cholesterol. As a consequence of markedly elevated plasma and tissue sitosterol and campesterol levels, premature atherosclerosis develops.
In this multicenter, double-blind, randomized, placebo-controlled study, we examined whether treatment with ezetimibe, an inhibitor of cholesterol absorption, reduces plant sterol levels in patients with sitosterolemia. After a 3-week placebo run-in, 37 patients were randomized to receive placebo (n=7) or ezetimibe 10 mg/d (n=30) for 8 weeks. Sitosterol concentrations decreased by 21% (P |
| doi_str_mv | 10.1161/01.CIR.0000116766.31036.03 |
| format | Article |
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In this multicenter, double-blind, randomized, placebo-controlled study, we examined whether treatment with ezetimibe, an inhibitor of cholesterol absorption, reduces plant sterol levels in patients with sitosterolemia. After a 3-week placebo run-in, 37 patients were randomized to receive placebo (n=7) or ezetimibe 10 mg/d (n=30) for 8 weeks. Sitosterol concentrations decreased by 21% (P<0.001) in patients treated with ezetimibe compared with a nonsignificant 4% rise in those on placebo (between-group P<0.001). The reduction in sitosterol from baseline was progressive, with further decline observed at each subsequent biweekly visit. Campesterol also progressively declined, with a mean decrease after 8 weeks of 24% with ezetimibe and a mean increase of 3% with placebo treatment (between-group P<0.001). Reductions in plant sterol concentrations were similar irrespective of whether patients were undergoing concomitant treatment with resin or statin. Reductions in total sterols and apolipoprotein B were also observed. Ezetimibe was well tolerated, with no serious treatment-related adverse events or discontinuations due to adverse events being reported.
Ezetimibe produced significant and progressive reductions in plasma plant sterol concentrations in patients with sitosterolemia, consistent with the hypothesis that ezetimibe inhibits the intestinal absorption of plant sterols as well as cholesterol, leading to reductions in plasma concentrations.</description><identifier>ISSN: 0009-7322</identifier><identifier>ISSN: 1524-4539</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.CIR.0000116766.31036.03</identifier><identifier>PMID: 14769702</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Adolescent ; Adult ; Aged ; Anticholesteremic Agents - therapeutic use ; Apolipoproteins B - blood ; Arteriosclerosis - genetics ; Arteriosclerosis - prevention & control ; ATP Binding Cassette Transporter, Subfamily G, Member 5 ; ATP Binding Cassette Transporter, Subfamily G, Member 8 ; ATP-Binding Cassette Transporters - genetics ; Azetidines - therapeutic use ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Child ; Cholesterol - analogs & derivatives ; Cholesterol - blood ; Cholesterol, Dietary - pharmacokinetics ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Double-Blind Method ; Ezetimibe ; Female ; Genes, Recessive ; Humans ; Intestinal Absorption - drug effects ; Lipid Metabolism, Inborn Errors - blood ; Lipid Metabolism, Inborn Errors - complications ; Lipid Metabolism, Inborn Errors - drug therapy ; Lipoproteins - deficiency ; Lipoproteins - genetics ; Male ; Medical sciences ; Middle Aged ; Phytosterols - pharmacokinetics ; Sitosterols - blood ; Sitosterols - pharmacokinetics ; Treatment Outcome</subject><ispartof>Circulation (New York, N.Y.), 2004-03, Vol.109 (8), p.966-971</ispartof><rights>2004 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Mar 2 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c520t-efdb6621be20502fb81ea4439f399e7d40bfaad4863e87f5440a0fc6ac9be3c53</citedby><cites>FETCH-LOGICAL-c520t-efdb6621be20502fb81ea4439f399e7d40bfaad4863e87f5440a0fc6ac9be3c53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3674,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15576505$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14769702$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SALEN, G</creatorcontrib><creatorcontrib>VON BERGMANN, K</creatorcontrib><creatorcontrib>LÜTJOHANN, D</creatorcontrib><creatorcontrib>KWITEROVICH, P</creatorcontrib><creatorcontrib>KANE, J</creatorcontrib><creatorcontrib>PATEL, S. B</creatorcontrib><creatorcontrib>MUSLINER, T</creatorcontrib><creatorcontrib>STEIN, P</creatorcontrib><creatorcontrib>MUSSER, B</creatorcontrib><creatorcontrib>Multicenter Sitosterolemia Study Group</creatorcontrib><creatorcontrib>the Multicenter Sitosterolemia Study Group</creatorcontrib><title>Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Sitosterolemia is a recessively inherited disorder that results from mutations in either ABCG5 or G8 proteins, with hyperabsorption of dietary sterols and decreased hepatic excretion of plant sterols and cholesterol. As a consequence of markedly elevated plasma and tissue sitosterol and campesterol levels, premature atherosclerosis develops.
In this multicenter, double-blind, randomized, placebo-controlled study, we examined whether treatment with ezetimibe, an inhibitor of cholesterol absorption, reduces plant sterol levels in patients with sitosterolemia. After a 3-week placebo run-in, 37 patients were randomized to receive placebo (n=7) or ezetimibe 10 mg/d (n=30) for 8 weeks. Sitosterol concentrations decreased by 21% (P<0.001) in patients treated with ezetimibe compared with a nonsignificant 4% rise in those on placebo (between-group P<0.001). The reduction in sitosterol from baseline was progressive, with further decline observed at each subsequent biweekly visit. Campesterol also progressively declined, with a mean decrease after 8 weeks of 24% with ezetimibe and a mean increase of 3% with placebo treatment (between-group P<0.001). Reductions in plant sterol concentrations were similar irrespective of whether patients were undergoing concomitant treatment with resin or statin. Reductions in total sterols and apolipoprotein B were also observed. Ezetimibe was well tolerated, with no serious treatment-related adverse events or discontinuations due to adverse events being reported.
Ezetimibe produced significant and progressive reductions in plasma plant sterol concentrations in patients with sitosterolemia, consistent with the hypothesis that ezetimibe inhibits the intestinal absorption of plant sterols as well as cholesterol, leading to reductions in plasma concentrations.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Anticholesteremic Agents - therapeutic use</subject><subject>Apolipoproteins B - blood</subject><subject>Arteriosclerosis - genetics</subject><subject>Arteriosclerosis - prevention & control</subject><subject>ATP Binding Cassette Transporter, Subfamily G, Member 5</subject><subject>ATP Binding Cassette Transporter, Subfamily G, Member 8</subject><subject>ATP-Binding Cassette Transporters - genetics</subject><subject>Azetidines - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Child</subject><subject>Cholesterol - analogs & derivatives</subject><subject>Cholesterol - blood</subject><subject>Cholesterol, Dietary - pharmacokinetics</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Double-Blind Method</subject><subject>Ezetimibe</subject><subject>Female</subject><subject>Genes, Recessive</subject><subject>Humans</subject><subject>Intestinal Absorption - drug effects</subject><subject>Lipid Metabolism, Inborn Errors - blood</subject><subject>Lipid Metabolism, Inborn Errors - complications</subject><subject>Lipid Metabolism, Inborn Errors - drug therapy</subject><subject>Lipoproteins - deficiency</subject><subject>Lipoproteins - genetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Phytosterols - pharmacokinetics</subject><subject>Sitosterols - blood</subject><subject>Sitosterols - pharmacokinetics</subject><subject>Treatment Outcome</subject><issn>0009-7322</issn><issn>1524-4539</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkV1rFTEQhoNY7LH6F2Qp6N2uk--zXghyaLVQEIpeh2x2YlP245hkK_XXN-05eFpzMwzzzMu8eQk5pdBQquhHoM3m4qqB8kqvlWo4Ba4a4C_IikomaiF5-5KsCtDWmjN2TF6ndFNaxbV8RY6p0KrVwFbk6uwv5jCGDiv0Hl0OtzjcVRH7xWGqtoNNo30oU65SxjgPqQpTtbU54JRT9Sfk6yqFPO-GOAb7hhx5OyR8u68n5Of52Y_Nt_ry-9eLzZfL2kkGuUbfd0ox2iEDCcx3a4pWCN563raoewGdt7YXa8Vxrb0UAix4p6xrO-RO8hPyeae7XboRe1fuiXYw2xhGG-_MbIN5PpnCtfk13xrKuAZYF4EPe4E4_14wZTOG5HAoZnFektFUteXzoICn_4E38xKnYs4wyrQUXLYF-rSDXJxTiuj_XULBPORmgJqSmznkZh5zM8DL8runXg6r-6AK8H4P2OTs4KOdXEgHTkqtJEh-Dw7xo48</recordid><startdate>20040302</startdate><enddate>20040302</enddate><creator>SALEN, G</creator><creator>VON BERGMANN, K</creator><creator>LÜTJOHANN, D</creator><creator>KWITEROVICH, P</creator><creator>KANE, J</creator><creator>PATEL, S. B</creator><creator>MUSLINER, T</creator><creator>STEIN, P</creator><creator>MUSSER, B</creator><general>Lippincott Williams & Wilkins</general><general>American Heart Association, Inc</general><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>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20040302</creationdate><title>Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia</title><author>SALEN, G ; VON BERGMANN, K ; LÜTJOHANN, D ; KWITEROVICH, P ; KANE, J ; PATEL, S. B ; MUSLINER, T ; STEIN, P ; MUSSER, B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c520t-efdb6621be20502fb81ea4439f399e7d40bfaad4863e87f5440a0fc6ac9be3c53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Anticholesteremic Agents - therapeutic use</topic><topic>Apolipoproteins B - blood</topic><topic>Arteriosclerosis - genetics</topic><topic>Arteriosclerosis - prevention & control</topic><topic>ATP Binding Cassette Transporter, Subfamily G, Member 5</topic><topic>ATP Binding Cassette Transporter, Subfamily G, Member 8</topic><topic>ATP-Binding Cassette Transporters - genetics</topic><topic>Azetidines - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Child</topic><topic>Cholesterol - analogs & derivatives</topic><topic>Cholesterol - blood</topic><topic>Cholesterol, Dietary - pharmacokinetics</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Double-Blind Method</topic><topic>Ezetimibe</topic><topic>Female</topic><topic>Genes, Recessive</topic><topic>Humans</topic><topic>Intestinal Absorption - drug effects</topic><topic>Lipid Metabolism, Inborn Errors - blood</topic><topic>Lipid Metabolism, Inborn Errors - complications</topic><topic>Lipid Metabolism, Inborn Errors - drug therapy</topic><topic>Lipoproteins - deficiency</topic><topic>Lipoproteins - genetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Phytosterols - pharmacokinetics</topic><topic>Sitosterols - blood</topic><topic>Sitosterols - pharmacokinetics</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SALEN, G</creatorcontrib><creatorcontrib>VON BERGMANN, K</creatorcontrib><creatorcontrib>LÜTJOHANN, D</creatorcontrib><creatorcontrib>KWITEROVICH, P</creatorcontrib><creatorcontrib>KANE, J</creatorcontrib><creatorcontrib>PATEL, S. B</creatorcontrib><creatorcontrib>MUSLINER, T</creatorcontrib><creatorcontrib>STEIN, P</creatorcontrib><creatorcontrib>MUSSER, B</creatorcontrib><creatorcontrib>Multicenter Sitosterolemia Study Group</creatorcontrib><creatorcontrib>the Multicenter Sitosterolemia Study Group</creatorcontrib><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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SALEN, G</au><au>VON BERGMANN, K</au><au>LÜTJOHANN, D</au><au>KWITEROVICH, P</au><au>KANE, J</au><au>PATEL, S. B</au><au>MUSLINER, T</au><au>STEIN, P</au><au>MUSSER, B</au><aucorp>Multicenter Sitosterolemia Study Group</aucorp><aucorp>the Multicenter Sitosterolemia Study Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2004-03-02</date><risdate>2004</risdate><volume>109</volume><issue>8</issue><spage>966</spage><epage>971</epage><pages>966-971</pages><issn>0009-7322</issn><issn>1524-4539</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Sitosterolemia is a recessively inherited disorder that results from mutations in either ABCG5 or G8 proteins, with hyperabsorption of dietary sterols and decreased hepatic excretion of plant sterols and cholesterol. As a consequence of markedly elevated plasma and tissue sitosterol and campesterol levels, premature atherosclerosis develops.
In this multicenter, double-blind, randomized, placebo-controlled study, we examined whether treatment with ezetimibe, an inhibitor of cholesterol absorption, reduces plant sterol levels in patients with sitosterolemia. After a 3-week placebo run-in, 37 patients were randomized to receive placebo (n=7) or ezetimibe 10 mg/d (n=30) for 8 weeks. Sitosterol concentrations decreased by 21% (P<0.001) in patients treated with ezetimibe compared with a nonsignificant 4% rise in those on placebo (between-group P<0.001). The reduction in sitosterol from baseline was progressive, with further decline observed at each subsequent biweekly visit. Campesterol also progressively declined, with a mean decrease after 8 weeks of 24% with ezetimibe and a mean increase of 3% with placebo treatment (between-group P<0.001). Reductions in plant sterol concentrations were similar irrespective of whether patients were undergoing concomitant treatment with resin or statin. Reductions in total sterols and apolipoprotein B were also observed. Ezetimibe was well tolerated, with no serious treatment-related adverse events or discontinuations due to adverse events being reported.
Ezetimibe produced significant and progressive reductions in plasma plant sterol concentrations in patients with sitosterolemia, consistent with the hypothesis that ezetimibe inhibits the intestinal absorption of plant sterols as well as cholesterol, leading to reductions in plasma concentrations.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>14769702</pmid><doi>10.1161/01.CIR.0000116766.31036.03</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete |
| subjects | Adolescent Adult Aged Anticholesteremic Agents - therapeutic use Apolipoproteins B - blood Arteriosclerosis - genetics Arteriosclerosis - prevention & control ATP Binding Cassette Transporter, Subfamily G, Member 5 ATP Binding Cassette Transporter, Subfamily G, Member 8 ATP-Binding Cassette Transporters - genetics Azetidines - therapeutic use Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Child Cholesterol - analogs & derivatives Cholesterol - blood Cholesterol, Dietary - pharmacokinetics Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Double-Blind Method Ezetimibe Female Genes, Recessive Humans Intestinal Absorption - drug effects Lipid Metabolism, Inborn Errors - blood Lipid Metabolism, Inborn Errors - complications Lipid Metabolism, Inborn Errors - drug therapy Lipoproteins - deficiency Lipoproteins - genetics Male Medical sciences Middle Aged Phytosterols - pharmacokinetics Sitosterols - blood Sitosterols - pharmacokinetics Treatment Outcome |
| title | Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia |
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