Young Sup Byun1, Jun-Hee Lee2, Benoit J Arsenault3, Xiaohong Yang4, Weihang Bao5, David DeMicco5, Rachel Laskey5, Joseph L Witztum6, Sotirios Tsimikas7. 1. Division of Cardiovascular Diseases, University of California San Diego, La Jolla, California; Division of Cardiology, Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, South Korea. 2. Division of Cardiovascular Diseases, University of California San Diego, La Jolla, California; Division of Cardiology, Kang-Dong Sacred Heart Hospital, Hallym University Medical Center, Seoul, South Korea. 3. Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Quebec City, Quebec, Canada. 4. Division of Cardiovascular Diseases, University of California San Diego, La Jolla, California. 5. Pfizer, Inc., New York, New York. 6. Division of Endocrinology/Metabolism, University of California San Diego, La Jolla, California. 7. Division of Cardiovascular Diseases, University of California San Diego, La Jolla, California. Electronic address: stsimikas@ucsd.edu.
Abstract
BACKGROUND:Oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) is a biomarker of increased risk for major adverse cardiovascular events (MACE) in community cohorts, but its role in patients with stable coronary heart disease (CHD) is unknown. OBJECTIVES: This study sought to examine the relationship between these oxidative biomarkers and cardiovascular outcomes in patients with established CHD. METHODS: In a random sample from the TNT (Treating to New Targets) trial, OxPL-apoB levels were measured in 1,503 patients at randomization (after an 8-week run-in period taking atorvastatin 10 mg) and 1 year after being randomized to atorvastatin 10 or 80 mg. We examined the association between baseline levels of OxPL-apoB and MACE, defined as death from CHD, nonfatal myocardial infarction, resuscitation after cardiac arrest, and fatal/nonfatal stroke, as well as the effect of statin therapy on OxPL-apoB levels and MACE. RESULTS:Patients with events (n = 156) had higher randomization levels of OxPL-apoB than those without events (p = 0.025). For the overall cohort, randomization levels of OxPL-apoB predicted subsequent MACE (hazard ratio [HR]: 1.21; 95% confidence interval: 1.04 to 1.41; p = 0.018) per doubling and tertile 3 versus tertile 1 (hazard ratio: 1.69; 95% confidence interval [CI]: 1.14 to 2.49; p = 0.01) after multivariate adjustment for age, sex, body mass index, among others, and treatment assignment. In the atorvastatin 10-mg group, tertile 3 was associated with a higher risk of MACE compared to the first tertile (HR: 2.08; 95% CI: 1.20 to 3.61; p = 0.01) but this was not significant in the atorvastatin 80-mg group (HR: 1.40; 95% CI: 0.80 to 2.46; p = 0.24). CONCLUSIONS: Elevated OxPL-apoB levels predict secondary MACE in patients with stable CHD, a risk that is mitigated by atorvastatin 80 mg. (A Study to Determine the Degree of Additional Reduction in CV Risk in Lowering LDL Below Minimum Target Levels [TNT]; NCT00327691).
RCT Entities:
BACKGROUND: Oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) is a biomarker of increased risk for major adverse cardiovascular events (MACE) in community cohorts, but its role in patients with stable coronary heart disease (CHD) is unknown. OBJECTIVES: This study sought to examine the relationship between these oxidative biomarkers and cardiovascular outcomes in patients with established CHD. METHODS: In a random sample from the TNT (Treating to New Targets) trial, OxPL-apoB levels were measured in 1,503 patients at randomization (after an 8-week run-in period taking atorvastatin 10 mg) and 1 year after being randomized to atorvastatin 10 or 80 mg. We examined the association between baseline levels of OxPL-apoB and MACE, defined as death from CHD, nonfatal myocardial infarction, resuscitation after cardiac arrest, and fatal/nonfatal stroke, as well as the effect of statin therapy on OxPL-apoB levels and MACE. RESULTS:Patients with events (n = 156) had higher randomization levels of OxPL-apoB than those without events (p = 0.025). For the overall cohort, randomization levels of OxPL-apoB predicted subsequent MACE (hazard ratio [HR]: 1.21; 95% confidence interval: 1.04 to 1.41; p = 0.018) per doubling and tertile 3 versus tertile 1 (hazard ratio: 1.69; 95% confidence interval [CI]: 1.14 to 2.49; p = 0.01) after multivariate adjustment for age, sex, body mass index, among others, and treatment assignment. In the atorvastatin 10-mg group, tertile 3 was associated with a higher risk of MACE compared to the first tertile (HR: 2.08; 95% CI: 1.20 to 3.61; p = 0.01) but this was not significant in the atorvastatin 80-mg group (HR: 1.40; 95% CI: 0.80 to 2.46; p = 0.24). CONCLUSIONS: Elevated OxPL-apoB levels predict secondary MACE in patients with stable CHD, a risk that is mitigated by atorvastatin 80 mg. (A Study to Determine the Degree of Additional Reduction in CV Risk in Lowering LDL Below Minimum Target Levels [TNT]; NCT00327691).
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Authors: Ayelet Gonen; Soo-Ho Choi; Phuong Miu; Colin Agatisa-Boyle; Daniel Acks; Angela M Taylor; Coleen A McNamara; Sotirios Tsimikas; Joseph L Witztum; Yury I Miller Journal: J Lipid Res Date: 2018-12-18 Impact factor: 5.922
Authors: Fleur M van der Valk; Siroon Bekkering; Jeffrey Kroon; Calvin Yeang; Jan Van den Bossche; Jaap D van Buul; Amir Ravandi; Aart J Nederveen; Hein J Verberne; Corey Scipione; Max Nieuwdorp; Leo A B Joosten; Mihai G Netea; Marlys L Koschinsky; Joseph L Witztum; Sotirios Tsimikas; Niels P Riksen; Erik S G Stroes Journal: Circulation Date: 2016-08-05 Impact factor: 29.690
Authors: Matthew T Mefford; Santica M Marcovina; Vera Bittner; Mary Cushman; Todd M Brown; Michael E Farkouh; Sotirios Tsimikas; Keri L Monda; J Antonio G López; Paul Muntner; Robert S Rosenson Journal: J Lipid Res Date: 2019-09-11 Impact factor: 5.922