Renin-angiotensin system and haemostasis gene polymorphisms and outcome after coronary artery bypass graft surgery.
BACKGROUND
Coronary artery bypass graft surgery is associated with a considerable 2-year mortality rate. Gene polymorphisms of the renin-angiotensin system may be associated with the risk of hypertension and cardiovascular disease. The angiotensin I-converting enzyme DD genotype has recently been identified as independent predictor of the outcome after coronary artery bypass graft surgery. Genetic factors of the clotting system may be related to the risk of myocardial infarction and restenosis after coronary interventions. The aims of the present study were to investigate whether gene polymorphisms of the renin-angiotensin system (angiotensinogen 235 M/T, angiotensin II type 1 receptor 1166 A/C) or the clotting system (glycoprotein IIIa PlA1/PlA2 and factor V Leiden 1691 G/A) are associated with the outcome after coronary artery bypass grafting.


METHODS
A study population of 247 patients was followed-up 2 years after coronary artery bypass graft surgery. The primary end-point was total mortality. The secondary end-point was mortality from cardiac cause or the need for myocardial revascularization (percutaneous coronary interventions or recurrent surgery) during follow-up. Geno typing was performed by polymerase chain reaction- and restriction fragment length polymorphism-based techniques.


RESULTS
An older age and the non-use of the internal mammary artery graft were identified as independent predictors of the primary end-point after coronary artery bypass grafting. A decreased left ventricular ejection fraction was an independent predictor for the secondary end-point. No association was found between any of the genetic factors and the outcomes after coronary artery bypass graft surgery in the main factor regression models. However, the angiotensin II type 1 receptor 1166 A/C gene polymorphism modulated the effects of age on the primary end-point, and the angiotensinogen 235 M/T gene polymorphism modulated the effects of age on the secondary end-point.


CONCLUSIONS
We conclude that there are interactions between the angiotensin II type 1 receptor 1166 A/C as well as the angiotensinogen 235 M/T gene polymorphism and age with respect to the outcome after coronary artery bypass graft surgery. The glycoprotein IIIa PlA1/PlA2 and the factor V Leiden 1691 G/A gene polymorphisms were not associated with mid-term mortality or cardiac morbidity after coronary artery bypass grafting.
Völzke
Henry
H
Department of Epidemiology and Social Medicine, Ernst Moritz Arndt University, Walther Rathenau Str. 48, D-17487 Greifswald, Germany. voelzke@uni-greifswald.de
Kleine
Volker
V
Robinson
Daniel M
DM
Grimm
Rita
R
Hertwig
Sabine
S
Schwahn
Christian
C
Eckel
Lothar
L
Rettig
Rainer
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine; D000808:Angiotensinogen / Q000235:genetics; D001777:Blood Coagulation / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000097:blood* / Q000235:genetics* / Q000601:surgery; D003545:Cysteine; D005165:Factor V / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics; D008297:Male; D008715:Methionine; D008875:Middle Aged; D009200:Myocardial Contraction / Q000235:genetics; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D013318:Stroke Volume / Q000235:genetics; D013912:Threonine; D016896:Treatment Outcome
D039661:Integrin beta3; D044140:Receptor, Angiotensin, Type 1; C095381:factor V Leiden; D000808:Angiotensinogen; D013912:Threonine; D005165:Factor V; D008715:Methionine; D003545:Cysteine; D000409:Alanine