Genetic predictors of intensive lipid-lowering therapy efficacy and its anti-inflammatory effects in very high cardiovascular risk patients

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.

Stolichnaya Izdatelskaya Kompaniya
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  • 1 Peoples' Friendship University of Russia (RUDN University), Miklukho-Maklaya ul. 6, Moscow, 117198, Russian Federation
APOA1; CYP3A4; Inflammatory status; Intensive statin therapy; Predictors of response to statin therapy; Statins
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