Julian C van Capelleveen1, Sang-Rok Lee2, Rutger Verbeek1, John J P Kastelein1, Nicholas J Wareham3, Erik S G Stroes1, G Kees Hovingh1, Kay-Tee Khaw4, S Matthijs Boekholdt5, Joseph L Witztum6, Sotirios Tsimikas7. 1. Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. 2. Vascular Medicine Program, Sulpizio Cardiovascular Center, Division of Cardiology, Department of Medicine, University of California San Diego, La Jolla, CA, USA; Division of Cardiology, Chonbuk National University Hospital and Chonbuk School of Medicine, Jeonju, Korea. 3. Medical Research Council Epidemiology Unit, Cambridge, United Kingdom. 4. Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. 5. Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands. 6. Division of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, CA, USA. 7. Vascular Medicine Program, Sulpizio Cardiovascular Center, Division of Cardiology, Department of Medicine, University of California San Diego, La Jolla, CA, USA. Electronic address: stsimikas@ucsd.edu.
Abstract
BACKGROUND: Plasma apolipoprotein C-III (apoC-III) levels are associated with coronary artery disease (CAD) risk. OBJECTIVE: To assess whether lipoprotein-associated apoC-III levels predict risk of CAD events. METHODS: apoC-III associated with apoB, apoAI, and Lp(a) (apoCIII-apoB, apoCIII-apoAI, and apoCIII-Lp(a), respectively) were measured using high-throughput chemiluminescent enzyme-linked immunoassays in 2711 subjects (1879 controls and 832 cases with CAD) in the European Prospective Investigation into Cancer and Nutrition-Norfolk prospective population study with 7.4 years of follow-up. These measures were correlated with a variety of lipid measurements and the presence of CAD. The indices of "total apoCIII-apoB" and "total apoCIII-apoAI" were derived by multiplying plasma apoB and apoAI, respectively. RESULTS: apoCIII-apoB (P = .001), apoCIII-Lp(a) (P < .001), apoCIII-apoAI (P = .005) were higher in cases vs controls; tended to correlate positively with body mass index, hsCRP, apoC-III, low-density lipoprotein (LDL) cholesterol, triglycerides, remnant cholesterol, very low density lipoprotein, LDL and high-density lipoprotein particle number and very low density lipoprotein size; but negatively with LDL and high-density lipoprotein particle size (P < .001 for all). apoCIII-apoB, apoCIII-apoAI, apoCIII-Lp(a), total apoCIII-Lp(a), and total apoCIII-apoB were predictors of CAD after adjustment of age, sex, body mass index, smoking, diabetes, hypertensive and lipid-lowering drug use, but they lost their significance after further adjustment of lipid and lipoprotein variables. CONCLUSIONS: This study suggests that enzyme-linked immunoassay-measured lipoprotein-associated apoC-III markers reflect atherogenic lipid particles but do not independently predict risk of CAD events.
BACKGROUND: Plasma apolipoprotein C-III (apoC-III) levels are associated with coronary artery disease (CAD) risk. OBJECTIVE: To assess whether lipoprotein-associated apoC-III levels predict risk of CAD events. METHODS:apoC-III associated with apoB, apoAI, and Lp(a) (apoCIII-apoB, apoCIII-apoAI, and apoCIII-Lp(a), respectively) were measured using high-throughput chemiluminescent enzyme-linked immunoassays in 2711 subjects (1879 controls and 832 cases with CAD) in the European Prospective Investigation into Cancer and Nutrition-Norfolk prospective population study with 7.4 years of follow-up. These measures were correlated with a variety of lipid measurements and the presence of CAD. The indices of "total apoCIII-apoB" and "total apoCIII-apoAI" were derived by multiplying plasma apoB and apoAI, respectively. RESULTS:apoCIII-apoB (P = .001), apoCIII-Lp(a) (P < .001), apoCIII-apoAI (P = .005) were higher in cases vs controls; tended to correlate positively with body mass index, hsCRP, apoC-III, low-density lipoprotein (LDL) cholesterol, triglycerides, remnant cholesterol, very low density lipoprotein, LDL and high-density lipoprotein particle number and very low density lipoprotein size; but negatively with LDL and high-density lipoprotein particle size (P < .001 for all). apoCIII-apoB, apoCIII-apoAI, apoCIII-Lp(a), total apoCIII-Lp(a), and total apoCIII-apoB were predictors of CAD after adjustment of age, sex, body mass index, smoking, diabetes, hypertensive and lipid-lowering drug use, but they lost their significance after further adjustment of lipid and lipoprotein variables. CONCLUSIONS: This study suggests that enzyme-linked immunoassay-measured lipoprotein-associated apoC-III markers reflect atherogenic lipid particles but do not independently predict risk of CAD events.
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Authors: Benjamin F Voight; Gina M Peloso; Marju Orho-Melander; Ruth Frikke-Schmidt; Maja Barbalic; Majken K Jensen; George Hindy; Hilma Hólm; Eric L Ding; Toby Johnson; Heribert Schunkert; Nilesh J Samani; Robert Clarke; Jemma C Hopewell; John F Thompson; Mingyao Li; Gudmar Thorleifsson; Christopher Newton-Cheh; Kiran Musunuru; James P Pirruccello; Danish Saleheen; Li Chen; Alexandre F R Stewart; Arne Schillert; Unnur Thorsteinsdottir; Gudmundur Thorgeirsson; Sonia Anand; James C Engert; Thomas Morgan; John Spertus; Monika Stoll; Klaus Berger; Nicola Martinelli; Domenico Girelli; Pascal P McKeown; Christopher C Patterson; Stephen E Epstein; Joseph Devaney; Mary-Susan Burnett; Vincent Mooser; Samuli Ripatti; Ida Surakka; Markku S Nieminen; Juha Sinisalo; Marja-Liisa Lokki; Markus Perola; Aki Havulinna; Ulf de Faire; Bruna Gigante; Erik Ingelsson; Tanja Zeller; Philipp Wild; Paul I W de Bakker; Olaf H Klungel; Anke-Hilse Maitland-van der Zee; Bas J M Peters; Anthonius de Boer; Diederick E Grobbee; Pieter W Kamphuisen; Vera H M Deneer; Clara C Elbers; N Charlotte Onland-Moret; Marten H Hofker; Cisca Wijmenga; W M Monique Verschuren; Jolanda M A Boer; Yvonne T van der Schouw; Asif Rasheed; Philippe Frossard; Serkalem Demissie; Cristen Willer; Ron Do; Jose M Ordovas; Gonçalo R Abecasis; Michael Boehnke; Karen L Mohlke; Mark J Daly; Candace Guiducci; Noël P Burtt; Aarti Surti; Elena Gonzalez; Shaun Purcell; Stacey Gabriel; Jaume Marrugat; John Peden; Jeanette Erdmann; Patrick Diemert; Christina Willenborg; Inke R König; Marcus Fischer; Christian Hengstenberg; Andreas Ziegler; Ian Buysschaert; Diether Lambrechts; Frans Van de Werf; Keith A Fox; Nour Eddine El Mokhtari; Diana Rubin; Jürgen Schrezenmeir; Stefan Schreiber; Arne Schäfer; John Danesh; Stefan Blankenberg; Robert Roberts; Ruth McPherson; Hugh Watkins; Alistair S Hall; Kim Overvad; Eric Rimm; Eric Boerwinkle; Anne Tybjaerg-Hansen; L Adrienne Cupples; Muredach P Reilly; Olle Melander; Pier M Mannucci; Diego Ardissino; David Siscovick; Roberto Elosua; Kari Stefansson; Christopher J O'Donnell; Veikko Salomaa; Daniel J Rader; Leena Peltonen; Stephen M Schwartz; David Altshuler; Sekar Kathiresan Journal: Lancet Date: 2012-05-17 Impact factor: 79.321
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