Genetic polymorphism, medical therapy and sequential cardiac function in patients with heart failure.
BACKGROUND
Functional variants of angiotensin-converting enzyme (ACE) gene may be associated with response to therapy in patients with heart failure (HF).


OBJECTIVE
To test the hypothesis of differences in sequential echocardiographic evaluations of left ventricular ejection fraction in patients with HF on medical therapy, including ACE inhibitors in relation to insertion (I) / deletion (D) polymorphism of the ACE gene.


METHODS
We studied 168 patients (mean age 43.3+/-10.1 years), 128 (76.2%) men, with HF and sequential echocardiograms. The I/D polymorphism was determined by polymerase chain reaction. Left ventricular ejection fraction (LVEF) was analyzed comparatively to genotypes. More than 90% of patients were on ACE inhibitors.


RESULTS
There was a significantly greater increase in mean LVEF in patients with the D allele compared to patients with the II genotype (p=0.01) after a mean follow-up of 38.9 months. The D allele was associated with an increase of 8.8% in mean LVEF over the same period. Furthermore, there was a tendency toward a D allele "copy number" effect on the increase of mean LVEF over time: a 3.5% difference in LVEF variation between patients with the II and the ID genotypes (p = 0.03) and a 5% difference between patients with the II and DD genotypes (p=0.02).


CONCLUSIONS
ACE gene deletion polymorphism may be operative in response to medical treatment that included ACE inhibitors in patients with HF. Further controlled studies may contribute to better understanding of genetic influences on response to therapy.
Cuoco
Marco Antonio Romeo
MA
Heart Institute (InCor), University of São Paulo Medical School, São Paulo - Brazil. marcocuoco@cardiol.br
Pereira
Alexandre Costa
AC
Mota
Glória de Fátima Alves da
Gde F
Krieger
José Eduardo
JE
Mansur
Alfredo José
AJ
D000328:Adult; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006333:Heart Failure / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D016277:Ventricular Function, Left / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D055815:Young Adult
D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A