Impact of angiotensin-converting enzyme gene polymorphism on neurohormonal responses to high- versus low-dose enalapril in advanced heart failure.
BACKGROUND
The impact of angiotensin-converting enzyme (ACE) gene polymorphism on neurohormonal dose response to ACE inhibitor therapy is unclear.


METHODS
ACE Insertion (I) or Deletion (D) genotype was determined in 74 patients with chronic heart failure who were randomly assigned to receive either high-dose or low-dose enalapril over a period of 6 months. Monthly pre-enalapril and post-enalapril neurohormone levels (serum ACE activity (sACE), plasma angiotensin II (A-II), plasma renin activity (PRA), and serum aldosterone (ALDO) were compared between genotype subgroups and between patients who received high- or low-dose enalapril within each genotype subgroup.


RESULTS
At baseline, predose/postdose sACE and postdose PRA were significantly higher in the DD genotype. At 6-month follow-up, postdose sACE was reduced in a dose-dependent fashion in all three genotypes (P < .05). However, predose and postdose ALDO and A-II levels did not differ between each genotype subgroup at baseline or by enalapril dose within each genotype subgroup. ALDO escape and A-II reactivation were not affected by ACE genotype or enalapril dosage.


CONCLUSIONS
Predose sACE were consistently higher in the DD genotype when compared with ID or II subgroups. Despite a dose-dependent suppression of sACE, there were no observed statistically significant differences in ALDO and A-II suppression or escape with escalating doses of enalapril within each subgroup.
Tang
W H Wilson
WH
Kaufman Center for Heart Failure, Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. tangw@ccf.org
Vagelos
Randall H
RH
Yee
Yin-Gail
YG
Fowler
Michael B
MB
D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004656:Enalapril / Q000008:administration & dosage*; D005260:Female; D005838:Genotype; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000097:blood*; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D012083:Renin / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D018377:Neurotransmitter Agents; D000804:Angiotensin II; D000450:Aldosterone; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A; D012083:Renin