Effect of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene on response to angiotensin-converting enzyme inhibitors in patients with heart failure.
There is marked interindividual variation in serum and tissue angiotensin-converting enzyme (ACE) levels for which the insertion (I)/deletion (D) polymorphism in intron 16 of the ACE gene is a marker. ACE inhibitors have important effects on morbidity and mortality in heart failure. The influence of this polymorphism on the response to ACE inhibitors in patients with heart failure is not known. We studied response by ACE genotype of 34 subjects in a randomised, double-blind, crossover study comparing 6 weeks of lisinopril (10 mg, o.d.) or captopril (25 mg, t.d.s.) on 24-h blood pressure (BP) profile and on renal function in patients with symptomatic heart failure [mean left ventricular ejection fraction (LVEF), 24%]. Glomerular filtration rate (GFR), 99mTc diethylenetriaminepentaacetic acid (DTPA), and ambulatory 24-h mean arterial pressure (MAP; Spacelabs 90207) were assessed at the beginning and end of treatment periods. There was a significant relation between ACE genotype and change in MAP with captopril (mm Hg; DD group, -0.5; ID, -4.7; II, -7.4; p = 0.02) but not to lisinopril (mm Hg DD, -6.0; ID, -6.6; II, -7.4; p = 0.89) in these patients. There was no significant relation between genotype and change in GFR with captopril (percentage change from baseline: DD, +7.9; ID, +13.1; II, -0.6; p = 0.45) or lisinopril (percentage change from baseline: DD, -0.1; ID, -3.0; II, -13.3; p = 0.39), but the decline in renal function tended to be greatest in II subjects. Whereas the results are not conclusive, there may be a significant interaction between ACE genotype and response to ACE inhibitors in patients with heart failure.
O'Toole
L
L
Department of Cardiology, Western General Hospital, Edinburgh, Scotland.
Stewart
M
M
Padfield
P
P
Channer
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D005260:Female; D017353:Gene Deletion; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D017706:Lisinopril / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011311:Pressoreceptors / Q000187:drug effects / Q000378:metabolism; D011446:Prospective Studies; D016037:Single-Blind Method; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A