{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T16:16:02Z","timestamp":1778688962779,"version":"3.51.4"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,1,18]],"date-time":"2017-01-18T00:00:00Z","timestamp":1484697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Extended\u2010release niacin (ERN) is the most effective agent for increasing high\u2010density lipoprotein\u2013cholesterol (HDL\u2010C). Having previously identified anti\u2010HDL antibodies, we investigated whether ERN affected the antioxidant capacity of HDL and whether ERN was associated with the production of antibodies against HDL (aHDL) and apolipoprotein A\u2010I (aApoA\u2010I).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty\u2010one patients older than 18\u00a0years, with HDL\u2010C\u00a0\u226440\u00a0mg dl<jats:sup>\u20131<\/jats:sup> (men) or \u226450\u00a0mg dl<jats:sup>\u20131<\/jats:sup> (women) were randomly assigned to receive daily ERN (<jats:italic>n<\/jats:italic>\u00a0=\u00a010) or placebo (<jats:italic>n<\/jats:italic>\u00a0=\u00a011) for two sequential 12\u2010week periods, with 4\u00a0weeks of wash\u2010out before cross\u2010over. Primary outcome was change of paraoxonase\u20101 (PON1) activity and secondary outcomes were changes in aHDL and aApoA\u2010I antibodies. Clinical Trial Unique Identifier: EudraCT 2006\u2013006889\u201042.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The effect of ERN on PON1 activity was nonsignificant (coefficient estimate 20.83\u00a0U\u00a0l<jats:sup>\u20131<\/jats:sup>, 95% confidence interval [CI] \u20139.88 to 51.53; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.184). ERN was associated with an increase in HDL\u2010C levels (coefficient estimate 5.21\u00a0mg dl<jats:sup>\u20131<\/jats:sup>, 95% CI 1.16 to 9.25; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.012) and its subclasses HDL2 (coefficient estimate 2.46\u00a0mg dl<jats:sup>\u20131<\/jats:sup>, 95% CI 0.57 to 4.34; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.011) and HDL3 (coefficient estimate 2.73\u00a0mg dl<jats:sup>\u20131<\/jats:sup>, 95% CI 0.47 to 4.98; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.018). ERN was significantly associated with the production of aApoA\u2010I antibodies (coefficient estimate 0.25\u00a0\u03bcg\u00a0ml<jats:sup>\u20131<\/jats:sup>, 95% CI 0.09\u20130.40; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.001). aApoA\u2010I titres at baseline were correlated with decreased PON activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The rise in HDL\u2010C achieved with ERN was not matched by improved antioxidant capacity, eventually hampered by the emergence of aApoA\u2010I antibodies. These results may explain why Niacin and other lipid lowering agents fail to reduce cardiovascular risk.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13198","type":"journal-article","created":{"date-parts":[[2016,11,28]],"date-time":"2016-11-28T01:16:37Z","timestamp":1480295797000},"page":"1002-1010","source":"Crossref","is-referenced-by-count":26,"title":["Extended\u2010release niacin increases anti\u2010apolipoprotein A\u2010I antibodies that block the antioxidant effect of high\u2010density lipoprotein\u2013cholesterol: the EXPLORE clinical trial"],"prefix":"10.1111","volume":"83","author":[{"given":"Joana R.","family":"Batuca","sequence":"first","affiliation":[{"name":"CEDOC, NOVA Medical School | Faculdade de Ci\u00eancias M\u00e9dicas Universidade NOVA de Lisboa  Lisbon Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta C.","family":"Amaral","sequence":"additional","affiliation":[{"name":"CEDOC, NOVA Medical School | Faculdade de Ci\u00eancias M\u00e9dicas Universidade NOVA de Lisboa  Lisbon Portugal"},{"name":"Department of Medicine IV \/ Immune\u2010mediated Systemic Diseases Unit Fernando Fonseca Hospital  Amadora Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catarina","family":"Favas","sequence":"additional","affiliation":[{"name":"Department of Medicine IV \/ Immune\u2010mediated Systemic Diseases Unit Fernando Fonseca Hospital  Amadora Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filipe S.","family":"Paula","sequence":"additional","affiliation":[{"name":"CEDOC, NOVA Medical School | Faculdade de Ci\u00eancias M\u00e9dicas Universidade NOVA de Lisboa  Lisbon Portugal"},{"name":"Department of Medicine IV \/ Immune\u2010mediated Systemic Diseases Unit Fernando Fonseca Hospital  Amadora Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul R. 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