Effect of atorvastatin on lipid profile in patients with coronary heart disease depending on the genotype ɛ2/ɛ3/ɛ4 apolipoprotein E gene polimorphism and body weight

Abstract

Objective. To investigate the effect of atorvastatin on lipid profile in patients with coronary heart disease (CHD), depending on the genotype for ɛ2/ɛ3/ɛ4 apolipoprotein E (apoE) gene polymorphism and body weight. Materials and methods. The study involved 150 patients with CHD. Research ɛ2/ɛ3/ɛ4 apoE gene polymorphism (rs7412 and rs429358) was performed by PCR followed by restriction fragment length analysis. The determination of blood lipids was performed at baseline and after 1 month of treatment. Diagnosis and treatment of coronary artery disease was by Order of the Ministry of Health of Ukraine № 436 from 03.07.2006. All patients received basic therapy, which included: anticoagulants, antiplatelet agents, β-blockers, angiotensin-converting enzyme inhibitors, antianginal agents and statins (atorvastatin 40 mg daily). Statistical analysis of the results was performed using SPSS 17.0. Results and discussion. In patients with CHD most common among homozygotes are ɛ3/ɛ3 genotype (62.7 %), and among heterozygotes ‒ ɛ3/ɛ4 genotype (21.3 %). It was found that in patients with CHD indicators of total cholesterol, very low density lipoprotein cholesterol (VLDL-С), triglycerides (TG) and atherogenic index (AI) were significantly higher and the rate of high density lipoprotein cholesterol (HDL-C) significantly lower compared with the control group (р<0,001). The content of low density lipoprotein cholesterol (LDL-C) was higher in patients with coronary artery disease compared with the control group, but statistically significant differences were found (p>0,05). Found that patients with ɛ4/ɛ4 genotype for ɛ2/ ɛ3/ɛ4 apoE gene polymorphism to treat the contents of HDL-Cl was significantly lower, and IA probably higher compared to ɛ3/ɛ4, ɛ3/ɛ3 and ɛ2/ɛ3 genotypes (p=0,015, p=0,013 respectively). The content of total cholesterol, LDL-C, VLDL-C, LDL-C, TG and IA after 1 month of treatment was significantly lower and the content of HDL-C significantly higher in patients with ɛ3/ɛ3, ɛ3/ɛ4, ɛ2/ɛ3 and ɛ4/ɛ4 genotypes (р<0,0001). In patients with ɛ3/ɛ3 genotype atorvastatin treatment was associated with a decrease in total cholesterol content of 13 %, VLDL-C ‒ by 16,7 %, TG ‒ by 15,4 %, IA ‒ 29,4 % and increased HDL-C by 20 % compared to the original content. The content of LDL-C significantly decreased in patients with ɛ3/ɛ3 genotype by 23,3%, and in patients with ɛ2/ɛ3, ɛ3/ɛ4 and ɛ4/ɛ4 genotypes ‒ 20 %, 18,8 % and 13,8 % respectively. It is proved that in patients with coronary artery disease with different weights atorvastatin treatment revealed a probable reduction in total cholesterol content, VLDL-C, LDL-C, TG, IA and significant increase in HDL-C content compared with the rates for treatment (р<0,0001). In patients with normal body weight after 1 month of treatment revealed a probable decrease in VLDL-C content of 20 %, TG ‒ by 13,6 %, and in patients with excessive weight ‒ reducing the amount of total cholesterol by 14,3 % and IA ‒ 29,7 %. The content of HDL-C increased by 20 % in patients with obesity and excessive weight, and in patients with normal body weight ‒ 9,1 %. Investigated the content of LDL-C in patients with excessive weight and normal body weight decreased by 21,9 % and 21,2 % respectively, and in patients with obesity ‒ by 17,9 %, but did not reach the target value. Conclusion. It was established that hypolipidemic effectiveness depended on the genotype for ɛ2/ɛ3/ɛ4 apoE gene polymorphism and was highest in the presence ɛ3/ɛ3 genotype. This is supported by probable reduction in total cholesterol content of 13%, VLDL-С ‒ by 16.7%, LDL-С ‒ by 23.3%, TG ‒ by 15.4% and likely increasing of HDL-С by 20% from baseline compared to other studied genotypes. Lipid-lowering efficacy was higher in patients with excessive weight and normal body weight evidenced likely reducing the amount of total cholesterol by 14.3 %, LDL-С ‒ by 21.9 %, IA ‒ 29.7 % and increase HDL-С content by 20 % of the benchmarks in patients with excessive weight and possible decline VLDL-С content of 20 %, TG ‒ 13.6 % of benchmarks in patients with normal body weight compared with patients who suffered from obesity.