ABCA1 impacts athero-thrombotic risk and 10-year survival in a contemporary secondary prevention setting |
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Authors: | Regieli Jakub J Doevendans Pieter A Grobbee Diederick E Zwinderman Aeilko H van der Graaf Yolanda Kastelein John J P Jukema J Wouter |
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Institution: | aUniversity Medical Center Utrecht, Department of Cardiology, The Netherlands;bUniversity Medical Center Utrecht, Juliuscenter for Health Sciences and Primary Care, The Netherlands;cAcademical Medical Center Amsterdam, Department of Clinical Epidemiology, The Netherlands;dAcademical Medical Center Amsterdam, Department of Vascular Medicine, The Netherlands;eInteruniversity Cardiology Institute of the Netherlands (ICIN/KNAW), Leiden University Medical Center, Department of Cardiology, The Netherlands;fDurrer Center for Cardiogenetic Research, Amsterdam, The Netherlands |
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Abstract: | ObjectivesWe prospectively investigated the effects of ATP-binding cassette protein-1 (ABCA1) variants on long-term clinical outcome in patients with coronary artery disease (CAD).BackgroundABCA1 is implicated in the etiology of atherothrombosis and may offer a target to reduce cardiovascular risk. However, the impact of ABCA1 on recurrent cardiovascular disease in a secondary prevention setting is as of yet unknown.MethodsWe studied cause-specific 10-year mortality and quantitative coronary angiography data from the Regression GRowth Evaluation Statin Study (REGRESS), comprising 884 male CAD patients genotyped for promoter variants encompassing a proximal regulatory region (rs2422493, rs1800976, rs2740483 and rs1800977). Kaplan–Meier, proportional hazards and haplotype analyses were used to ascertain single-variant and multi-marker effects on absolute risk and extent of CAD.ResultsProtection from 10-year vascular death could be attributed to the rs2422493 genotype (available in 639 patients) T allele with absolute risk decreasing stepwise from 12.2% to 8.6% to 4.7% per each added allele copy, HR 0.64, p = 0.03 and HR 0.53, p = 0.04 in the TGCC haplotype context. The TGCC (p = 0.04) and TCCT (p = 0.003) haplotypes exhibited less extensive CAD.ConclusionsOn a background of contemporary secondary prevention, variation in the ABCA1 promoter influences 10-year risk of vascular death and angiographic extent of CAD in men. These insights contribute to identification of patients sharing a specific prognosis, understanding of its etiological basis and development of strategies of risk reduction in CAD. |
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Keywords: | Abbreviations: CAD coronary artery disease ABCA1 ATP-binding cassette protein A1 REGRESS Regression Growth Evaluation Statin Study QCA quantitative coronary angiography MSD mean segment diameter MOD minimal obstruction diameter LD linkage disequilibrium ZNF202 zinc finger 202 HR hazard ratio HDL high-density lipoprotein |
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