Article

Absence of an interaction between the angiotensin-converting enzyme insertion-deletion polymorphism and pravastatin on cardiovascular disease in high-risk hypertensive patients: The Genetics of Hypertension-Associated Treatment (GenHAT) study

Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht University, Utrecht, Utrecht, Netherlands
American heart journal (Impact Factor: 4.56). 02/2007; 153(1):54-8. DOI: 10.1016/j.ahj.2006.10.019
Source: PubMed

ABSTRACT 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.
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.
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).
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.

Download full-text

Full-text

Available from: Anke-Hilse Maitland-van der Zee, Aug 09, 2015
0 Followers
 · 
167 Views
  • Source
    • "Although this is a positive step, research to identify and validate pharmacogenomic markers of differential statin therapeutic effect has received much greater attention. In comparison, at least 10 pharmacogenomic substudies of statin RCTs have assessed markers of efficacy [Ference et al. 2011; Hoffmann et al. 2011; Maitland-van der Zee et al. 2007]. "
    03/2014; 5(2):62-66. DOI:10.1177/2042098613520030
  • [Show abstract] [Hide abstract]
    ABSTRACT: Use of lipid-lowering agents, mainly statins, is a proven strategy to prevent cardiovascular disease events. Because most of the beneficial effect of statins is accounted for by the improved lipid profile, more than 40 genes have been studied to ascertain whether variation therein modulates lipid response or prevention of cardiovascular disease during statin therapy. In addition, recent studies have also shown that genetic variation may stratify pleiotropic statin effects. Although this review briefly covers the pharmacogenetic implications on biochemical markers such as low-density lipoprotein cholesterol, it mainly focuses on recent findings (after 2005) on cardiovascular disease outcomes during statin therapy. Pharmacogenomic analysis of large trials of statin treatment is becoming a predominant trend. Another future direction is genome-wide analysis, which will reveal additional candidate genes to be further tested in prospective trials. The results so far are preliminary, and successful replication of the findings is needed in large unrelated populations before the evidence for any polymorphism is solid enough for clinical applications. KeywordsPharmacogenomics-Pharmacogenetics-Statins-Cardiovascular disease
    Current Cardiovascular Risk Reports 03/2010; 4(2):150-158. DOI:10.1007/s12170-010-0081-0
  • [Show abstract] [Hide abstract]
    ABSTRACT: The angiotensin-converting enzyme (ACE) catalyzes the formation of angiotensin II and the breakdown of bradykinin into inactive products. The insertion/deletion (I/D) polymorphism affects the activity of the enzyme, with the DD genotype being responsible for the highest activity of the enzyme. Meta-analysis of 11 studies including white persons showed that the DD genotype was a risk factor for ischemic stroke. No such correlation was found in an Asian population. Studies on different etiologies or intermediate phenotypes of ischemic stroke did not bring univocal results. There are still no convincing data on whether the I/D polymorphism of the ACE gene is a risk factor for spontaneous intracerebral hemorrhage and intracranial aneurysms, ruptured or unruptured. Several pharmacogenetic studies analyzed the influence of the ACE I/D polymorphism on the response to acute stroke therapy (thrombolysis) or prevention strategies (lifestyle modification and treatment of vascular risk factors). Presently, however, there is no consensus on whether the efficacy of these therapies is affected by the ACE gene I/D polymorphism.
    Current Treatment Options in Cardiovascular Medicine 07/2007; 9(3):198-204. DOI:10.1007/s11936-007-0013-6
Show more