TY - JOUR
T1 - ABCA1 impacts athero-thrombotic risk and 10-year survival in a contemporary secondary prevention setting
AU - Regieli, Jakub J.
AU - Doevendans, Pieter A.
AU - Grobbee, Diederick E.
AU - Zwinderman, Aeilko H.
AU - van der Graaf, Yolanda
AU - Kastelein, John J. P.
AU - Jukema, J. Wouter
PY - 2011
Y1 - 2011
N2 - 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). 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. 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. 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. 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
AB - 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). 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. 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. 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. 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
U2 - https://doi.org/10.1016/j.atherosclerosis.2011.07.008
DO - https://doi.org/10.1016/j.atherosclerosis.2011.07.008
M3 - Article
C2 - 21840005
SN - 0021-9150
VL - 218
SP - 457
EP - 463
JO - Atherosclerosis
JF - Atherosclerosis
IS - 2
ER -