Genetic predictors of unfavorable prognosis in patients with low and moderate cardiovascular risk with high adherence to treatment

Abstract Aim To evaluate the contribution of gene polymorphism to the development of unfavorable prognosis in patients with low and moderate cardiovascular risk (CVR) with high adherence to treatment. Materials and methods The study included 364 patients with low and moderate cardiovascular disease (CVD) without target organ damage (TOD) and associated clinical conditions. At baseline, patients underwent a clinical examination, laboratory and instrumental diagnostics to exclude TOD, genotype assessment using markers AGT Thr174Met, GNB3 C825T, MTHFR C677T, MTRR Ile22Met. Average age - 53.03±2.35 years. The observation lasted 6.41±0.54 years. An unfavorable prognosis in patients was defined as death, including from CVD, and CVD-related hospitalization. Depending on occurrence of the predicted event, patients were divided into two groups. The 1st group consisted of 35 patients (9.62%) with events that occurred, the 2nd group included 329 patients (90.38%) without events. Of the total number of predicted events during the observation period, total mortality accounted for 2.47%, including cardiovascular mortality - 1.1%, and hospitalization for CVD - 8.24%. Results The groups initially didn’t differ in basic clinical and demographic characteristics, comorbid pathology and risk factors, drug therapy and treatment adherence. The groups were comparable in terms of indicators reflecting the structural and functional state of the kidneys, arteries and heart. The overall incidence of pathological polymorphism among patients with an unfavorable prognosis was 23.51%. Patients in the groups did not differ significantly in the frequency of occurrence of polymorphisms of the AGT and GNB3 genes, MTRR and ApoE genes. In Group 1, a high incidence of pathological homozygotes (T/T genotype) of the MTHFR gene was observed (p 0.001). An unfavorable prognosis was also associated with the polymorphism of the PRARα gene in a pathological homozygous form. The frequency of the pathological genotype C/C was higher in patients with predictable events occurring, and the frequency of normal G/G polymorphism was higher in Group 2 (p 0.001). Correlation analysis showed direct moderate interrelationship between the presence of an unfavorable prognosis and the MTHFR gene polymorphism - T/T genotype (r=0.30; p0.05), and the PRARA gene polymorphism - S/S genotype (r=0.31; p0.05). In the presence of MTHFR gene polymorphism in the form of a pathological homozygote (T/T genotype), the chance of developing an unfavorable prognosis increased 11 times (OR=11.04,95%CI =4.12-29.58), and in the presence of PPARα in the form of a pathological homozygote (C/C genotype) - more than 8 times (OR=8.67,95%CI=3.83-19.59). Conclusions The risk of developing an unfavorable prognosis in patients with low and moderate CVR with high adherence to treatment is associated with the presence of polymorphism of the MTHFR and PPARα genes in the form of a pathological homozygote.