CETP RS247616 POLYMORPHISM IN PATIENTS WITH CHRONIC HEART FAILURE AND CORONARY HEART DISEASE: TRAITS OF LIPID METABOLISM AND EFFECTIVENESS OF STATIN THERAPY

Abstract

Abstract. Introduction. Dyslipidemia is a modifiable risk factor for cardiovascular complications in patients with chronic ischemia-induced heart failure. Being the best-known class of drugs, statins effectively reduce cardiovascular mortality in all age groups. Effectiveness of using lipid-lowering drugs is determined by some factors, including genetic ones. Polymorphism rs247616 of the CETP (cholesterol ester transfer protein) gene is associated with changing high-density lipoprotein levels in blood serum. Aim. To analyze the clinical parameters and effectiveness of lipid-lowering therapy in stable chronic ischemia-induced heart failure patients with the rs247616 polymorphism of the CETP gene. Materials and Methods. We examined 517 patients with chronic ischemia-induced heart failure, aged 66.4±10.4 years, of both sexes. A genetic control of 118 conditionally healthy individuals was included. We analyzed the allele frequency of the CETP rs247616 occurrences, clinical characteristics, statin administration frequency, dose range, and achieving the lipid metabolism goals, including in relation to the genotype. Results and Discussion. Statins were prescribed to 28.8% of patients with chronic heart failure, with 42.3% receiving the minimum dosage and 35.6% receiving the average therapeutic dosage. Frequency of TT-genotype and T allele of the CETP rs247616 was higher in patients with chronic heart failure compared with controls (13.2% and 10.2%, p=0.026, 35% and 26.7%, p=0.014). It was found that CC-genotype has a protective effect against the development of chronic heart failure (CC vs CT+TT, OR=0.57, 95%CI:0.38-0.86). In patients with CC-genotype chronic heart failure, a lower level of high-density lipoproteins was observed (1.12±0.37 and 1.25±0.37 mmol/l, p=0.012), as compared to the carriers of T allele (CT+TT). Percentage of individuals with total cholesterol levels below 4.5 mmol/l (33.3%, 29.7%, and 37.5%) and triglyceride levels < 1.7 mmol/l (36.5%, 25%, and 37.5%) did not differ between CC-, CT-, and TT-genotypes, respectively. There is a trend towards an increase in the proportion of the carriers of T allele and TT-genotype with low-density lipoprotein levels < 1.8 mmol/l (30.8%, 45.5%, and 50%) and non-high-density lipoproteins levels<2.6 mmol/l (29.4%, 31.2%, and 50%). Conclusions. Effectiveness of statin therapy is low: 38.1 % of patients had the total cholesterol levels < 4.5 mmol/l, 11% had low-density lipoprotein levels <1.8 mmol/l, 50.6% had triglyceride levels <1.7 mmol/l, and 12.2% of patients had non-high-density lipoprotein levels <2.6 mmol/l. Protective effect of CC-genotype was found regarding the genesis of chronic heart failure.