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

• Published in: Rat͡s︡ionalʹnai͡a︡ farmakoterapii͡a︡ v kardiologii Vol. 13; no. 4; pp. 525 - 531
• Main Authors: Vorobyeva, M. A., Azova, M. M., Gigani, O. O., Garmash, I. V., Villevalde, S. V., Kobalava, Zh. D.
• Format: Journal Article
• Language: English
• Published: Столичная издательская компания 01.01.2017
• Subjects: apoa1; cyp3a4; inflammatory status; intensive statin therapy; predictors of response to statin therapy; statins
• ISSN: 1819-6446; 2225-3653
• DOI: 10.20996/1819-6446-2017-13-4-525-531

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.