Calvin Yeang1, Ming-Yow Hung2, Young-Sup Byun3, Paul Clopton4, Xiaohong Yang1, Joseph L Witztum5, Sotirios Tsimikas6. 1. Division of Cardiovascular Diseases, Sulpizio Cardiovascular Center, Department of Medicine, University of California, La Jolla, CA, USA. 2. Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan. 3. Division of Cardiology, Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, South Korea. 4. San Diego Veteran's Administration Medical Center, La Jolla, CA, USA. 5. Division of Endocrinology and Metabolism, Department of Medicine, University of California, La Jolla, CA, USA. 6. Division of Cardiovascular Diseases, Sulpizio Cardiovascular Center, Department of Medicine, University of California, La Jolla, CA, USA. Electronic address: stsimikas@ucsd.edu.
Abstract
BACKGROUND:Oxidized phospholipids (OxPL) on apolipoprotein B-100 (OxPL-apoB) reflect the biological activity of lipoprotein(a) (Lp[a]) and predict cardiovascular disease events. However, studies with statins and low-fat diets show increases in OxPL-apoB and Lp(a). OBJECTIVE: This study evaluated changes in OxPL-apoB and Lp(a) with extended-release niacin (N), ezetimibe/simvastatin (E/S) and combination E/S/N. A systematic literature review of previously published trials, measuring both OxPL-apoB and Lp(a) after therapeutic interventions, was also performed. METHODS:OxPL-apoB and Lp(a) were measured in 591 patients at baseline and 24 weeks after therapy with N, E/S, or E/S/N in a previously completed randomized trial of hypercholesterolemic patients. The literature review included 12 trials and 3896 patients evaluating statins, low-fat diets, antisense to apolipoprotein(a) and lipid apheresis. RESULTS:Niacin decreased OxPL-apoB levels (median [interquartile range]; 3.5 [2.2-9.2] nM to 3.1 [1.8-7.2] nM, P < .01) and Lp(a) (10.9 [4.6-38.4] to 9.3 [3.1-32.9] mg/dL, P < .01). In contrast, E/S and E/S/N significantly increased OxPL-apoB (3.5 [2.1-7.8] to 4.9 [3.0-11.1] nM, P < .01) and (3.3 [1.9-9.3] to 4.3 [2.6-11.2] nM, P < .01), respectively and Lp(a) (11.5 [6.1-36.4] to 14.9 [6.6-54.6] mg/dL, P < .01) and (11.3 [5.4-43.8] to 11.6 [5.9-52.8] mg/dL, P < .01), respectively. The systematic review of statins and diet demonstrated 23.8% and 21.3% mean increases in OxPL-apoB and 10.6% and 19.4% increases in Lp(a), respectively. However 44.1% and 52.0% decreases in OxPL-apoB and Lp(a), respectively, were present with Lp(a)-lowering therapies. CONCLUSIONS: This study demonstrates differential changes in OxPL-apoB and Lp(a) with various lipid-lowering approaches. These changes in OxPL-apoB and Lp(a) may provide insights into the results and interpretation of recent cardiovascular disease outcomes trials.
RCT Entities:
BACKGROUND: Oxidized phospholipids (OxPL) on apolipoprotein B-100 (OxPL-apoB) reflect the biological activity of lipoprotein(a) (Lp[a]) and predict cardiovascular disease events. However, studies with statins and low-fat diets show increases in OxPL-apoB and Lp(a). OBJECTIVE: This study evaluated changes in OxPL-apoB and Lp(a) with extended-release niacin (N), ezetimibe/simvastatin (E/S) and combination E/S/N. A systematic literature review of previously published trials, measuring both OxPL-apoB and Lp(a) after therapeutic interventions, was also performed. METHODS: OxPL-apoB and Lp(a) were measured in 591 patients at baseline and 24 weeks after therapy with N, E/S, or E/S/N in a previously completed randomized trial of hypercholesterolemicpatients. The literature review included 12 trials and 3896 patients evaluating statins, low-fat diets, antisense to apolipoprotein(a) and lipid apheresis. RESULTS:Niacin decreased OxPL-apoB levels (median [interquartile range]; 3.5 [2.2-9.2] nM to 3.1 [1.8-7.2] nM, P < .01) and Lp(a) (10.9 [4.6-38.4] to 9.3 [3.1-32.9] mg/dL, P < .01). In contrast, E/S and E/S/N significantly increased OxPL-apoB (3.5 [2.1-7.8] to 4.9 [3.0-11.1] nM, P < .01) and (3.3 [1.9-9.3] to 4.3 [2.6-11.2] nM, P < .01), respectively and Lp(a) (11.5 [6.1-36.4] to 14.9 [6.6-54.6] mg/dL, P < .01) and (11.3 [5.4-43.8] to 11.6 [5.9-52.8] mg/dL, P < .01), respectively. The systematic review of statins and diet demonstrated 23.8% and 21.3% mean increases in OxPL-apoB and 10.6% and 19.4% increases in Lp(a), respectively. However 44.1% and 52.0% decreases in OxPL-apoB and Lp(a), respectively, were present with Lp(a)-lowering therapies. CONCLUSIONS: This study demonstrates differential changes in OxPL-apoB and Lp(a) with various lipid-lowering approaches. These changes in OxPL-apoB and Lp(a) may provide insights into the results and interpretation of recent cardiovascular disease outcomes trials.
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