Published Online
on August 18, 2003

A more recent version of this article appeared on September 1, 2003

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Submitted on June 3, 2003
Revised on June 23, 2003

The ACE Gene I/D Polymorphism Is Not Associated With the Blood Pressure and Cardiovascular Benefits of ACE Inhibition

Stephen B. Harrap^*; Christophe Tzourio; François Cambien; Odette Poirier; Segolene Raoux; John Chalmers; Neil Chapman; Samuel Colman; Solenn Leguennec; Stephen MacMahon; Bruce Neal; Takayoshi Ohkubo; Mark Woodward; and for the PROGRESS Collaborative Group*

From the Department of Physiology (S.B.H.), University of Melbourne, Melbourne, Australia; the National Institute of Health and Medical Research (C.T., S.L.), INSERM U360, Hopital de la Salpetriere, Paris, France; INSERM U525 (F.C., O.P., S.R.), Faculté de Médecine, Paris, France; and the Institute for International Health (J.C., N.C., S.C., S.M., B.N., T.O., M.W.), University of Sydney, Sydney, Australia.

^* To whom correspondence should be addressed. E-mail: s.harrap{at}unimelb.edu.au.

Abstract--The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene might have consequences for the risks of vascular diseases. We examined the ACE genotype and the effects of a perindopril-based blood pressure-lowering regimen on macrovascular events, dementia, and cognitive decline among hypertensive and nonhypertensive patients with a history of cerebrovascular disease. ACE I/D genotypes were measured in 5688 of 6105 individuals with previous stroke or transient ischemic attack who participated in the PROGRESS trial. The DD genotype was significantly (P<0.0001) less frequent in Asian subjects (Chinese and Japanese, 14.7%) than in non-Asian subjects (32.0%). Controlling for racial background, there were no associations between ACE genotypes and cerebrovascular disease history or cardiovascular risk factors, including baseline blood pressure. The ACE genotype was not associated with the long-term risks of stroke, cardiac events, mortality, dementia, or cognitive decline; neither did the ACE genotype predict the blood pressure reduction associated with the use of the ACE inhibitor perindopril. Similarly, there was no evidence that the ACE genotype modified the relative benefits of ACE inhibitor-based therapy over placebo. This study provides no evidence that in patients with cerebrovascular disease, knowledge of ACE genotype is useful for predicting either the risk of disease or the benefits of perindopril-based blood pressure-lowering treatment.

Key words: genes • blood pressure • stroke • coronary disease • clinical trials

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