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GENETIC PREDICTORS OF INTENSIVE LIPID-LOWERING THERAPY EFFICACY AND ITS ANTI-INFLAMMATORY EFFECTS IN VERY HIGH CARDIOVASCULAR RISK PATIENTS

https://doi.org/10.20996/1819-6446-2017-13-4-525-531

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Abstract

Aim. To study the anti-inflammatory effects of intensive lipid-lowering therapy and genetic predictors of its effectiveness in patients with very high cardiovascular risk.

Material and methods. 58 patients with a history of cardiovascular disease and low-density lipoprotein cholesterol (LDL-C)>1.8 mmol/l or non-highdensity lipoprotein cholesterol (non-HDL-C)>2.6 mmol/l (mean age 61.9±8.6 (M±SD) years, 62.1% of men) were included into the study. Polymorphism Phe189Ser of the CYP3A4 (gene encoding cytochrome P4503A4, CYP3A4*17, rs4987161) and APOA1 (gene encoding apolipoprotein A): -75G/A in the promoter region (rs670) and +83C/T in the 5'-untranslated region (rs5069) was determined in all patients. Inflammatory status (high-sensitivity C-reactive protein (hsCRP), monocyte chemoattractant protein (MCP-1) and soluble vascular adhesion molecule (sVCAM-1)) was assessed initially and after 4 weeks of treatment with atorvastatin 80 mg/day. The results were considered statistically significant at p<0.05.

Results. 16 (27.6%) patients achieved LDL-C<1.8 mmol/l, 21 (37.6%) patients – non-HDL-C<2.6 mmol/l. The carriership of the allele -75G of the APOA1 gene was associated with failure to achieve the target level of the non-HDL-C (Fisher's exact test p<0.05 (bilateral), p<0.01 (one-sided)). The levels of hsCRP, MCP-1 and sVCAM-1 significantly decreased by 46.8, 19.2 and 13.2%, respectively (p=0.0001). In the ROC analysis the level of MCP-1<471 pg/ml predicted the achievement of the target level of non-HDL-C with a sensitivity of 53.3% and a specificity of 90%.

Conclusion. Intensive lipid-lowering therapy in patients with a very high cardiovascular risk is accompanied by a pronounced anti-inflammatory effect. The baseline level of MCP-1<471 pg/ml is associated with the achievement of the target values of non-HDL-C. The carriership of the allele (-75)G of the APOA1 gene is associated with the lack of achievement of the target level of non-HDL-C during intensive lipid-lowering therapy and can be considered as a predictor of resistance to statins. 

About the Authors

M. A. Vorobyeva
Peoples’ Friendship University of Russia (RUDN University)
Russian Federation

MD, Post-Graduate Student, Chair of Internal Medicine with Course of Cardiology and Functional Diagnostics, Institute of Medicine,

Miklukho-Maklaya ul. 6, Moscow, 117198



M. M. Azova
Peoples’ Friendship University of Russia (RUDN University)
Russian Federation

PhD (Biology), Associate Professor, Head of Chair of Biology and General Genetics, Institute of Medicine,

Miklukho-Maklaya ul. 6, Moscow, 117198



O. O. Gigani
Peoples’ Friendship University of Russia (RUDN University)
Russian Federation

PhD (Biology), Associate Professor, Chair of Biology and General Genetics, Institute of Medicine,

Miklukho-Maklaya ul. 6, Moscow, 117198



I. V. Garmash
Peoples’ Friendship University of Russia (RUDN University)
Russian Federation

MD, PhD, Associate Professor, Chair of Internal Medicine with Course of Cardiology and Functional Diagnostics, Institute of Medicine,

Miklukho-Maklaya ul. 6, Moscow, 117198



S. V. Villevalde
Peoples’ Friendship University of Russia (RUDN University)
Russian Federation

MD, PhD, Professor, Chair of Internal Medicine with Course of Cardiology and Functional Diagnostics, Institute of Medicine,

Miklukho-Maklaya ul. 6, Moscow, 117198



Zh. D. Kobalava
Peoples’ Friendship University of Russia (RUDN University)
Russian Federation

MD, PhD, Professor, Head of Chair of Internal Medicine with Course of Cardiology and Functional Diagnostics, Head of Chair of Internal Medicine, Cardiology and Clinical Pharmacology, Institute of Medicine,

Miklukho-Maklaya ul. 6, Moscow, 117198



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For citation:


Vorobyeva M.A., Azova M.M., Gigani O.O., Garmash I.V., Villevalde S.V., Kobalava Z.D. GENETIC PREDICTORS OF INTENSIVE LIPID-LOWERING THERAPY EFFICACY AND ITS ANTI-INFLAMMATORY EFFECTS IN VERY HIGH CARDIOVASCULAR RISK PATIENTS. Rational Pharmacotherapy in Cardiology. 2017;13(4):525-531. (In Russ.) https://doi.org/10.20996/1819-6446-2017-13-4-525-531

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ISSN 1819-6446 (Print)
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