{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:41:54Z","timestamp":1790502114308,"version":"4.1.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Lp(a) [lipoprotein (a)] is composed of apoB (apolipoprotein B) and apo(a) [apolipoprotein (a)] and is an independent risk factor for cardiovascular disease and aortic stenosis. In clinical trials, anacetrapib, a CETP (cholesteryl ester transfer protein) inhibitor, causes significant reductions in plasma Lp(a) levels. We conducted an exploratory study to examine the mechanism for Lp(a) lowering by anacetrapib.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              We enrolled 39 participants in a fixed-sequence, double-blind study of the effects of anacetrapib on the metabolism of apoB and high-density lipoproteins. Twenty-nine patients were randomized to atorvastatin 20 mg\/d, plus placebo for 4 weeks, and then atorvastatin plus anacetrapib (100 mg\/d) for 8 weeks. The other 10 subjects were randomized to double placebo for 4 weeks followed by placebo plus anacetrapib for 8 weeks. We examined the mechanisms of Lp(a) lowering in a subset of 12 subjects having both Lp(a) levels &gt;20 nmol\/L and more than a 15% reduction in Lp(a) by the end of anacetrapib treatment. We performed stable isotope kinetic studies using\n              <jats:sup>2<\/jats:sup>\n              H\n              <jats:sub>3<\/jats:sub>\n              -leucine at the end of each treatment to measure apo(a) fractional catabolic rate and production rate. Median baseline Lp(a) levels were 21.5 nmol\/L (interquartile range, 9.9\u2013108.1 nmol\/L) in the complete cohort (39 subjects) and 52.9 nmol\/L (interquartile range, 38.4\u2013121.3 nmol\/L) in the subset selected for kinetic studies. Anacetrapib treatment lowered Lp(a) by 34.1% (\n              <jats:italic>P<\/jats:italic>\n              \u22640.001) and 39.6% in the complete and subset cohort, respectively. The decreases in Lp(a) levels were because of a 41% reduction in the apo(a) production rate, with no effects on apo(a) fractional catabolic rate.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Anacetrapib reduces Lp(a) levels by decreasing its production.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Trial Registration\u2014<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              . Unique identifier: NCT00990808.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.117.309549","type":"journal-article","created":{"date-parts":[[2017,7,21]],"date-time":"2017-07-21T01:10:23Z","timestamp":1500599423000},"page":"1770-1775","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":91,"title":["CETP (Cholesteryl Ester Transfer Protein) Inhibition With Anacetrapib Decreases Production of Lipoprotein(a) in Mildly Hypercholesterolemic Subjects"],"prefix":"10.1161","volume":"37","author":[{"given":"Tiffany","family":"Thomas","sequence":"first","affiliation":[{"name":"From the Columbia University, New York (T.T., W.K., R.R., S.H., H.N.G., G.R.-S.); Merck &amp; Co, Inc, Kenilworth, NJ (H.Z., Y.L., P.J., J.A.W., B.H., S.F.P., T.R., A.O.J.-L., D.E.G.); University of Washington, Seattle (S.M.M.); and University of Pennsylvania, Philadelphia (D.J.R., J.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haihong","family":"Zhou","sequence":"additional","affiliation":[{"name":"From the Columbia University, New York (T.T., W.K., R.R., S.H., H.N.G., G.R.-S.); Merck &amp; Co, Inc, Kenilworth, NJ (H.Z., Y.L., P.J., J.A.W., B.H., S.F.P., T.R., A.O.J.-L., D.E.G.); University of Washington, Seattle (S.M.M.); and University of Pennsylvania, Philadelphia (D.J.R., J.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wahida","family":"Karmally","sequence":"additional","affiliation":[{"name":"From the Columbia University, New York (T.T., W.K., R.R., S.H., H.N.G., G.R.-S.); Merck &amp; Co, Inc, Kenilworth, NJ (H.Z., Y.L., P.J., J.A.W., B.H., S.F.P., T.R., A.O.J.-L., D.E.G.); University of Washington, Seattle (S.M.M.); and University of Pennsylvania, Philadelphia (D.J.R., J.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajasekhar","family":"Ramakrishnan","sequence":"additional","affiliation":[{"name":"From the Columbia University, New York (T.T., W.K., R.R., S.H., H.N.G., G.R.-S.); Merck &amp; Co, Inc, Kenilworth, NJ (H.Z., Y.L., P.J., J.A.W., B.H., S.F.P., T.R., A.O.J.-L., D.E.G.); University of Washington, Seattle (S.M.M.); and University of Pennsylvania, Philadelphia (D.J.R., J.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Holleran","sequence":"additional","affiliation":[{"name":"From the Columbia University, New York (T.T., W.K., R.R., S.H., H.N.G., G.R.-S.); Merck &amp; Co, Inc, Kenilworth, NJ (H.Z., Y.L., P.J., J.A.W., B.H., S.F.P., T.R., A.O.J.-L., D.E.G.); University of Washington, Seattle (S.M.M.); and University of Pennsylvania, Philadelphia (D.J.R., J.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"From the Columbia University, New York (T.T., W.K., R.R., S.H., H.N.G., G.R.-S.); Merck &amp; Co, Inc, Kenilworth, NJ (H.Z., Y.L., P.J., J.A.W., B.H., S.F.P., T.R., A.O.J.-L., D.E.G.); University of Washington, Seattle (S.M.M.); and University of Pennsylvania, Philadelphia (D.J.R., J.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Jumes","sequence":"additional","affiliation":[{"name":"From the Columbia University, New York (T.T., W.K., R.R., S.H., H.N.G., G.R.-S.); Merck &amp; Co, Inc, Kenilworth, NJ (H.Z., Y.L., P.J., J.A.W., B.H., S.F.P., T.R., A.O.J.-L., D.E.G.); University of Washington, Seattle (S.M.M.); and University of Pennsylvania, Philadelphia (D.J.R., J.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Wagner","sequence":"additional","affiliation":[{"name":"From the Columbia University, New York (T.T., W.K., R.R., S.H., H.N.G., G.R.-S.); Merck &amp; Co, Inc, Kenilworth, NJ (H.Z., Y.L., P.J., J.A.W., B.H., S.F.P., T.R., A.O.J.-L., D.E.G.); University of Washington, Seattle (S.M.M.); and University of Pennsylvania, Philadelphia (D.J.R., J.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Hubbard","sequence":"additional","affiliation":[{"name":"From the Columbia University, New York (T.T., W.K., R.R., S.H., H.N.G., G.R.-S.); Merck &amp; Co, Inc, Kenilworth, NJ (H.Z., Y.L., P.J., J.A.W., B.H., S.F.P., T.R., A.O.J.-L., D.E.G.); University of Washington, Seattle (S.M.M.); and University of Pennsylvania, Philadelphia (D.J.R., J.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen F.","family":"Previs","sequence":"additional","affiliation":[{"name":"From the Columbia University, New York (T.T., W.K., R.R., S.H., H.N.G., G.R.-S.); Merck &amp; Co, Inc, Kenilworth, NJ (H.Z., Y.L., P.J., J.A.W., B.H., S.F.P., T.R., A.O.J.-L., D.E.G.); University of Washington, Seattle (S.M.M.); and University of Pennsylvania, Philadelphia (D.J.R., J.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Roddy","sequence":"additional","affiliation":[{"name":"From the Columbia University, New York (T.T., W.K., R.R., S.H., H.N.G., G.R.-S.); Merck &amp; Co, Inc, Kenilworth, NJ (H.Z., Y.L., P.J., J.A.W., B.H., S.F.P., T.R., A.O.J.-L., D.E.G.); University of Washington, Seattle (S.M.M.); and University of Pennsylvania, Philadelphia (D.J.R., J.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy O.","family":"Johnson-Levonas","sequence":"additional","affiliation":[{"name":"From the Columbia University, New York (T.T., W.K., R.R., S.H., H.N.G., G.R.-S.); Merck &amp; Co, Inc, Kenilworth, NJ (H.Z., Y.L., P.J., J.A.W., B.H., S.F.P., T.R., A.O.J.-L., D.E.G.); University of Washington, Seattle (S.M.M.); and University of Pennsylvania, Philadelphia (D.J.R., J.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Gutstein","sequence":"additional","affiliation":[{"name":"From the Columbia University, New York (T.T., W.K., R.R., S.H., H.N.G., G.R.-S.); Merck &amp; Co, Inc, Kenilworth, NJ (H.Z., Y.L., P.J., J.A.W., B.H., S.F.P., T.R., A.O.J.-L., D.E.G.); University of Washington, Seattle (S.M.M.); and University of Pennsylvania, Philadelphia (D.J.R., J.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santica M.","family":"Marcovina","sequence":"additional","affiliation":[{"name":"From the Columbia University, New York (T.T., W.K., R.R., S.H., H.N.G., G.R.-S.); Merck &amp; Co, Inc, Kenilworth, NJ (H.Z., Y.L., P.J., J.A.W., B.H., S.F.P., T.R., A.O.J.-L., D.E.G.); University of Washington, Seattle (S.M.M.); and University of Pennsylvania, Philadelphia (D.J.R., J.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Rader","sequence":"additional","affiliation":[{"name":"From the Columbia University, New York (T.T., W.K., R.R., S.H., H.N.G., G.R.-S.); Merck &amp; Co, Inc, Kenilworth, NJ (H.Z., Y.L., P.J., J.A.W., B.H., S.F.P., T.R., A.O.J.-L., D.E.G.); University of Washington, Seattle (S.M.M.); and University of Pennsylvania, Philadelphia (D.J.R., J.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry N.","family":"Ginsberg","sequence":"additional","affiliation":[{"name":"From the Columbia University, New York (T.T., W.K., R.R., S.H., H.N.G., G.R.-S.); Merck &amp; Co, Inc, Kenilworth, NJ (H.Z., Y.L., P.J., J.A.W., B.H., S.F.P., T.R., A.O.J.-L., D.E.G.); University of Washington, Seattle (S.M.M.); and University of Pennsylvania, Philadelphia (D.J.R., J.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Millar","sequence":"additional","affiliation":[{"name":"From the Columbia University, New York (T.T., W.K., R.R., S.H., H.N.G., G.R.-S.); 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