TY - JOUR
T1 - Absence of an interaction between the angiotensin-converting enzyme insertion-deletion polymorphism and pravastatin on cardiovascular disease in high-risk hypertensive patients
T2 - The Genetics of Hypertension-Associated Treatment (GenHAT) study
AU - Maitland-van der Zee, Anke Hilse
AU - Boerwinkle, Eric
AU - Arnett, Donna K.
AU - Davis, Barry R.
AU - Leiendecker-Foster, Catherine
AU - Miller, Michael B.
AU - Klungel, Olaf H.
AU - Ford, Charles E.
AU - Eckfeldt, John H
PY - 2007/1
Y1 - 2007/1
N2 - Background: The aim of this study was to determine whether the angiotensin-converting enzyme (ACE) insertion-deletion (ID) polymorphism interacts with pravastatin to modify the risk of coronary heart disease (CHD) and other cardiovascular end points in a large clinical trial. Methods: GenHAT is an ancillary study of the ALLHAT. The ACE ID genotyped population in the lipid-lowering arm of ALLHAT included 9467 participants randomly assigned to pravastatin (n = 4741) or to usual care (n = 4726). The efficacy of pravastatin in reducing the risk of primary outcome (all-cause mortality) and secondary outcomes (fatal CHD and nonfatal myocardial infarction, cardiovascular disease [CVD] mortality, CHD, stroke, other CVD, non-CVD mortality, stroke, and heart failure) was compared between the genotype strata (dominant model ID + II vs DD, additive model II vs ID vs DD), by examining an interaction term in a Cox proportional hazards model. Results: The relative risk of fatal CHD and nonfatal myocardial infarction among subjects randomized to pravastatin compared with subjects randomized to usual care was similar in subjects with the II genotype (hazard ratio [HR] 0.84, 95% CI 0.59-1.18), the ID genotype (HR 0.84, 95% CI 0.68-1.03), and the DD genotype (HR 0.99, 95% CI 0.77-1.27). Conclusions: We found no evidence that the ACE ID genotype was a major modifier of the efficacy of pravastatin in reducing the risk of cardiovascular events.
AB - Background: The aim of this study was to determine whether the angiotensin-converting enzyme (ACE) insertion-deletion (ID) polymorphism interacts with pravastatin to modify the risk of coronary heart disease (CHD) and other cardiovascular end points in a large clinical trial. Methods: GenHAT is an ancillary study of the ALLHAT. The ACE ID genotyped population in the lipid-lowering arm of ALLHAT included 9467 participants randomly assigned to pravastatin (n = 4741) or to usual care (n = 4726). The efficacy of pravastatin in reducing the risk of primary outcome (all-cause mortality) and secondary outcomes (fatal CHD and nonfatal myocardial infarction, cardiovascular disease [CVD] mortality, CHD, stroke, other CVD, non-CVD mortality, stroke, and heart failure) was compared between the genotype strata (dominant model ID + II vs DD, additive model II vs ID vs DD), by examining an interaction term in a Cox proportional hazards model. Results: The relative risk of fatal CHD and nonfatal myocardial infarction among subjects randomized to pravastatin compared with subjects randomized to usual care was similar in subjects with the II genotype (hazard ratio [HR] 0.84, 95% CI 0.59-1.18), the ID genotype (HR 0.84, 95% CI 0.68-1.03), and the DD genotype (HR 0.99, 95% CI 0.77-1.27). Conclusions: We found no evidence that the ACE ID genotype was a major modifier of the efficacy of pravastatin in reducing the risk of cardiovascular events.
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U2 - 10.1016/j.ahj.2006.10.019
DO - 10.1016/j.ahj.2006.10.019
M3 - Article
C2 - 17174637
AN - SCOPUS:33845299191
SN - 0002-8703
VL - 153
SP - 54
EP - 58
JO - American Heart Journal
JF - American Heart Journal
IS - 1
ER -