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Apoe polymorphism influence on the effectiveness of statin therapy and clinical re-sults of percutaneous coronary intervention in patients with coronary artery disease


Y.I. Buziashvili - Dr.Sc. (Med.), Professor, Academician of the Russian Academy of Sciences, Head of Clini-cal and Diagnostic Department, Bakoulev Scientific Center for Cardiovascular Surgery, Moscow
I.V. Koksheneva - Dr.Sc. (Med.), Senior Research Scientist, Department of Clinical and Diagnostic Department, Bakoulev Scientific Center for Cardiovascular Surgery, Moscow
M.A. Kakauridze - Post-graduate Student, Department of Clinical and Diagnostic Department, Bakoulev Scientific Center for Cardiovascular Surgery, Moscow
S.T. Abukov - Cardiologist, Department of Clinical and Diagnostic Department, Bakoulev Scientific Center for Cardiovascular Surgery, Moscow
I.A. Inauri - Cardiologist, Department of Clinical and Diagnostic Department, Bakoulev Scientific Center for Cardiovascular Surgery, Moscow
S.T. Matskeplishvili - Dr.Sc. (Med.), Professor, Corresponding Member of the Russian Academy of Sciences, Cardiologist, Lomonosov Moscow University Clinic

Polymorphism of АpоЕ gene is related to LDL-C and triglyceride levels, and also modifies effect of statin administration, that can influence the possibility of restenosis and clinical results following percutaneous coronary interventions (PCI).
To investigate the effect of ApoE gene polymorphism (ε-polymorphisms) on the effectiveness of statin therapy and clinical outcomes in patients with coronary artery disease undergoing percutaneous coronary interventions.
The study included 96 patients with coronary artery disease treated with PCI. Patients were followed for an average of 2,5±0,2 years after treatment. ApoE gene polymorphism at position 3937S/4075S, and T/T (rs429358 and rs7412) were studied. Patients were divided into 3 groups: Group 1 (10 patients) – e2 allele carriers, this group consisted of patients with genotypes ε2/ε2 and ε2/ε3; Group 2 (66 patients) – carriers of "wild" genotype ε3/ε3; Group 3 (20 patients) – carriers of the allele ε4, this group consisted of patients with genotype ε3/ε4 and ε4/ε4. In a cohort of patients included in this study, there were no genotype carriers of ε2/ε4.
ApoE gene polymorphism (rs429358 + rs7412) was associated with inadequate response to lipid-lowering therapy with sta-tins in medium-high doses in patients with coronary artery disease referred to percutaneous coronary interventions. The presence of the allele e4 and genotype ε3/ε4 was associated with insufficient reduction in LDL-cholesterol on statin therapy: e4 allele carriers OR:11.54; 95% CI:2,61-50,9; ε3/ε4 carriers OR:9.2; 95% CI:1,95-43,3; for genotype ε3/ε4 + ε4/ε4 OR:12.2; 95%CI:2,62-56,9. These associations were confirmed by comparative data from lipid status in carriers of different alleles of ApoE gene.
In patients with polymorphic alleles ApoE ε4 gene there is a tendency to increase the frequency of restenosis in long-term period after PCI, however, this trend did not reach statistical significance. E4 allele and genotype ε4 / ε4 and ε3 / ε4 showed no significant association with an increased risk of cardiovascular events after PCI.
Patients with polymorphic ε2 alleles of ApoE gene had lower incidence of cardiovascular events (angina+myocardial infarc-tion) at long-term follow-up following PCI (p=0.0001) and a lower incidence of restenosis and progression of coronary (p=0.037) compared to patients with other genotypes. But association of genotype ε2/ε2 with a reduced risk of developing cardiovascular events after PCI was not statistically significant: x2=14.0, p=0.0008; OR:0.22; 95%CI: 0,01-4,42.
The results indicate the significant influence of ApoE gene polymorphism on the effectiveness of statin therapy in patients with coronary artery disease. Identification of patients carrying ε4 allele having inadequate response to lipid-lowering ther-apy with statins may subsequently guide individual strategies for lipid-lowering therapy (higher doses of statins and/or combination therapy of statin+fibrate, statin+nicotinic acid; PCSK9 inhibitors, etc.) to improve PCI outcomes. Also, there is no protective effect of ε2 allele carrying in patients with coronary artery disease referred to PCI.

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