Homozygosity for angiotensinogen 235T variant increases the risk of myocardial infarction in patients with multi-vessel coronary artery disease

objective Molecular variants of the angiotensinogen (AGT) and the angiotens in II type 1 receptor(ATR) genes have been associated with the risk of coro nary artery disease (CAD) and myocardial infarction (MI), but data so far a vailable are conflicting. The primary object of the paper is to verify this possible association by a rigorous, angiographically controlled study in a large sample of patients with or without multi-vessel CAD. Design We designed a large case-control study in Italian patients candidate s for coronary artery bypass grafting, with angiographically documented mul ti-vessel CAD, compared to subjects with angiographically documented normal coronary arteries. Methods and results AGT M235T and ATR A1166C gene polymorphisms were analys ed in 699 subjects; 454 patients were candidates for coronary artery bypass grafting, having angiographically documented (mainly multi-vessel) CAD. An appropriate documentation of previous MI was obtained from 404/454 (89%, 2 47 with and 157 without MI). Subjects (n = 245) with angiographically docum ented normal coronary arteries, were included as control group (CAD-free gr oup). CAD patients had a substantial burden of conventional risk factors as compa red with controls free of coronary atherosclerosis. Age, gender, smoking ha bit and number of stenosed vessels were the only differences between patien ts with or without previous myocardial infarction, who were similarly expos ed to the other conventional risk factors (including hypertension). AGT M23 5T and ATR A1166C allele and genotype frequencies were similar between CAD and CAD-fre e patients. In the CAD group, AGT 235T allele was found more frequently in subjects with a previous myocardial infarction (0.494 versus 0.414; P less than or equal to 0.05). By logistic regression, homozygosity for AGT 235T v ariant appeared to confer 1.9-fold increased risk for MI in both the univar iate and the multivariate (adjusted for age, gender, smoking habit and numb er of stenosed vessels) model. Conclusions AGT 235T homozygous patients with multivessel CAD have an incre ased risk of myocardial infarction as compared with subjects with clinicall y similar phenotype but different genotype. J Hypertens 19:879-884 (C) 2001 Lippincott Williams & Wilkins.