The ACE gene I/D polymorphism is not associated with the blood pressure and cardiovascular benefits of ACE inhibition.
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.
Harrap
Stephen B
SB
Department of Physiology, University of Melbourne, Melbourne, Australia. s.harrap@unimelb.edu.au
Tzourio
Christophe
C
Cambien
François
F
Poirier
Odette
O
Raoux
Segolene
S
Chalmers
John
J
Chapman
Neil
N
Colman
Samuel
S
Leguennec
Solenn
S
MacMahon
Stephen
S
Neal
Bruce
B
Ohkubo
Takayoshi
T
Woodward
Mark
M
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D003072:Cognition Disorders / Q000150:complications; D003704:Dementia / Q000150:complications; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D020913:Perindopril / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D017384:Sequence Deletion; D013223:Statistics as Topic; D020521:Stroke / Q000150:complications; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D014652:Vascular Diseases / Q000150:complications
D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A; D020913:Perindopril