期刊
ATHEROSCLEROSIS
卷 218, 期 2, 页码 457-463出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2011.07.008
关键词
Coronary disease; Epidemiology; Lipoproteins; Prevention; Survival
资金
- Bristol Myers Squibb, NY, USA
- Netherlands Organisation for Health Research and Development (ZonMW) [920-03-367, 904-65-095]
- Interuniversity Cardiology Institute Netherlands (ICIN) [14]
- Bekalis Foundation
- Netherlands' Heart Foundation [2001D032]
Objectives: We prospectively investigated the effects of ATP-binding cassette protein-1 (ABCA1) variants on long-term clinical outcome in patients with coronary artery disease (CAD). Background: ABCA1 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. Methods: We 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. Results: Protection 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. Conclusions: On 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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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