POOR PROGNOSIS PREDICTOR IN ISCHEMIC HEART DISEASE PATIENTS WITH CONFIRMED HEMODYNAMICALLY SIGNIFICANT CORONARY ARTERY ATHEROSCLEROSIS IN THE DYNAMICS OF LONG OBSERVATION

Abstract

The purpose of the study - to determine the clinical-anamnestic, instrumental parameters, and genetic factors, that that determine the development of adverse cardiovascular events (ACVE) in patients with ischemic heart disease (IHD) with a verified hemodynamically significant coronary artery (CA) atherosclerosis at long follow-up.Materials and methods. The study involved 318 patients with IHD with the presence of hemodynamically significant stenoses (stenosis> 50%) at least one CA according to selective coronary angiography (SCG). Evaluation of patients included determination of the ankle-brachial index (ABI), Doppler sonography of the lower extremities vessels (LEV) and carotid artery (CARA) with a quantitative assessment of the intima-media thickness (IMT), carrying a load test by the modified Bruce protocol and determination of glomerular filtration rate (GFR) by MDRD. The observation period lasted (28,4 + 4,8) months. Study endpoints were cardiovascular death, myocardial infarction (MI), unstable angina, need for revascularization, and cerebrovascular accident. Study of the angiotensin converting enzyme (ACE) I/D polymorphism and endothelial NO-synthase (eNOS) gene promoter T-786S polymorphism was performed using polymerase chain reaction.Results and discussion . 82 (25.8%) patients in whom the study endpoints occurred were included in group I, 236 patients without ACVE - group II. According to odds ratios (OR) chance of developing ACVE in the examined patients was increased in the presence of hypertension (AH) (OR = 2,06, 95 % CI [1,05-3,84], p <0,05), diabetes mellitus (DM), type 2 (OR = 2,12, 95 % CI [1,15-3,92], p <0,05), abdominal obesity (OR = 1,82, 95 % CI [1,10-3,01], p <0,05), smoking (OR = 2,03, 95 % CI [1,21-3,36], p <0,05), family history of cardiovascular disease (CVD) early onset (OR = 1,81, 95 % CI [1,0-2,95], p <0,05), more than one MI in anamnesis (OR = 2,06, 95 % CI [1,11-3,84], p <0,05), reducing EF < 45% ( OR = 1,77, 95 % CI [1,05-2,99], p <0,05), decline in renal function (OR = 1,89, 95 % CI [1,1-3,25] p < 0.05), as well as by atherosclerotic lesions of CARA (OR = 2,28, 95 % CI [1,23-4,23], p <0,05) and LEV (OR = 1,93, 95 % CI [1,11-3,35], p <0,05), the lesions of three CA (OR = 1,77, 95 % CI [1,06-2,94], p <0,05) and diffuse type of lesion according SCG (OR = 3,56, 95 % CI [1,15-5,59], p <0,05). In the I patients group frequency of mutant DD genotype of ACE gene I/D polymorphism was greater than in Group II (37,8% vs 24,6%, p <0,05). The presence of DD genotype was associated with an increased likelihood of ACVE in patients with verified CA atherosclerosis (OR = 1,87, 95% CI [1,10-3,18], p = 0,03). The frequency of eNOS gene promoter T-786C polymorphism mutant CC genotype occurrence was also higher In the first patients group than in the II group (37.6% vs. 14,8%, p <0,05). Chance of poor prognosis for carriers of mutant CC genotype and C allele of eNOS gene promoter T-786C polymorphism was significantly higher (OR = 3,46, 95% CI [1,37-8,48], p = 0.014).Conclusions. An adverse cardiovascular events development in patients with stable IHD with verified coronary artery (CA) atherosclerosis is associated with the presence of arterial hypertension, type 2 diabetes mellitus, smoking, family history of CVD early onset, as well as more than one MI in anamnesis, with atherosclerotic lesions of the carotid arteries and blood vessels of the lower extremities, lesions of the three CA and diffuse type of lesion according to SCG, reduced left ventricular ejection fraction less than 45% and declining of renal function according to GFR. The DD genotype of angiotensin-converting enzyme I/D polymorphism and the CC genotype of endothelial NO-synthase gene T-786S promoter polymorphism associated with poor prognosis in patients with stable IHD. The probability of adverse cardiovascular events in the presence of these polymorphic markers increases in 1.87 and 3.46 times, respectively.