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

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

ASSESSMENT OF THE EFFECT OF ANESTHESIA METHODS ON HRV AND PAIN SYNDROME AFTER SEPTOPLASTY

Aims: to evaluate various methods of anesthesia during septoplasty for changes in heart rate variability (HRV) and acute pain syndrome in the early postoperative period. Patients and methods. All patients received local anesthesia with 2% procaine solution. In group 1(105 people) premedication was used with 2% promedol solution and 60 mg of ketorolac in the evening, in group 2 (108 people) -fentanyl, propofol, cisatracuria besylate, tranexamic acid, atropine and metoclopramide, in group 3 (78 people) - atracuria besylate, sodium thiopental, nitrous oxide and halothane. In groups 2 and 3, 100 mg of ketoprofen was administered intramuscularly in the evening on the day of surgery. The frequency domain of HRV was estimated per day. Pain was assessed using a visual analogue scale (VAS). Results. ULF and LF were significantly higher in groups 2 and 3 than in the local anesthetic group. VLF in the second group was significantly lower than in groups 1 and 3. Groups 2 and 3 had low HF. The VHF of group 2 was significantly lower than in groups 1 and 3, which also differed from each other - the VHF values in group 1 were higher than in group 2. Total power in group 2 was significantly lower than in groups 1 and 3. Pain syndrome was less pronounced in group 2. Conclusion. The following scheme may be less stressful when performing septopalstics for general anesthesia: fentanyl, propofol, cisatracuria besylate, tranexamic acid, atropine and metoclopramide