CORRECTION OF ENDOGENOUS RISK FACTORS FOR CORONARY HEART DISEASE

  • Authors: Kuznetsov A.1,2
  • Affiliations:
    1. "Moscow Regional Hospital of Prof. Rozanova V.N.", Moscow region, Russia
    2. Kursk State Medical University, Ministry of Health of the Russian Federation, Kursk, Russia
  • Issue: Vol 11, No 1 (2022): XVI МЕЖДУНАРОДНАЯ НАУЧНО-ПРАКТИЧЕСКАЯ КОНФЕРЕНЦИЯ МОЛОДЫХ УЧЕНЫХ-МЕДИКОВ
  • Pages: 24-25
  • Section: Результаты фундаментальных и прикладных исследований
  • URL: https://new.vestnik-surgery.com/index.php/2415-7805/article/view/7342

Cite item

Abstract

Relevance: for a long time, coronary heart disease (CHD) has been the main cause of death of the population worldwide [1]. In 2016, for the first time, "revolutionary" lipid-lowering drugs, monoclonal antibodies- inhibitors of the PCSK9 protein were used in practical medicine, allowing achieving the target values of low-density lipoprotein cholesterol of LDL cholesterol in more than 90% of patients [2]. Studies by various scientists have proved that the concentration of PCSK9 in women is higher than in men [3]. In addition, with age, the level of plasma PCSK9 in men decreases, and in women, on the contrary, increases, which is most likely due to the level of estrogens in the body [4].Objective: to evaluate the effect of estradiol on the expression of PSCK9 in patients with IHD Materials and methods: 39 men (average age 60.95±5.89 years) participated in the study IHD sufferers from a group of very high cardiovascular risk. Prior to the start of the study, for 8 weeks, all patients took a combination of the maximum tolerated dose of HMG-CoA Reductase inhibitor (Atorvastatin 80mg 1p / day) with an inhibitor of intestinal cholesterol absorption (Ezetemib) and did not reach the target values of LDL cholesterol < 1.4 mmol. After that, Alirocumab 150mg 1 injection per 14 days was added to the treatment (PRALUENT, SANOFI, France), followed by monitoring of LDL cholesterol and estradiol levels every 4 weeks. The median of the study was months. The program SPSS 23.0 (IBM USA) was used for statistical data processing.Results: at the start of the study, the average LDL cholesterol level was 2.28±0.08 mmol, the estradiol level was 149.13±87.3 pg/ml. A large variation in estradiol indicators (standard deviation) was associated with individual characteristics of the endocrine status of men. The use of Alirocumab showed high statistical significance after 4 weeks of using the drug (2 injections), the level of LDL cholesterol decreased by 34.2% and amounted to 1.5±0.1 mmol (p<0.001), the level of estradiol in the same control increased by 8.39% and did not show statistical significance (p=0.64). After 6 months of treatment, the LDL cholesterol level decreased by 43.86% 1.28±0.14 mmol (p<0.001), the estradiol level increased by 15.15% after 6 months of treatment (p=0.47). At the end of the study, after 12 months of treatment with PCSK9 inhibitors, the level of LDL cholesterol decreased by 49.56% from the baseline level and amounted to 1.15±0.15 mmol (p<0.001); the target values of LDL cholesterol reached 97.43% of patients (n=38). The estradiol level after 12 months of treatment with PCSK9 inhibitors was 162.64±86.14 pg/ml, increased by 19.37% from the baseline values and showed no statistical significance (p=0.39). In the correlation analysis, no significant relationship was found between the dynamics of LDL cholesterol reduction and an increase in estradiol levels.Conclusions: the revealed features of changes in endogenous risk factors in patients with coronary heart disease expand modern ideas about the role of PCSK9 inhibitors in the context of correction of atherogenic lipoprotein fractions.

Full Text

Relevance: for a long time, coronary heart disease (CHD) has been the main cause of death of the population worldwide [1]. In 2016, for the first time, "revolutionary" lipid-lowering drugs, monoclonal antibodies- inhibitors of the PCSK9 protein were used in practical medicine, allowing achieving the target values of low-density lipoprotein cholesterol of LDL cholesterol in more than 90% of patients [2]. Studies by various scientists have proved that the concentration of PCSK9 in women is higher than in men [3]. In addition, with age, the level of plasma PCSK9 in men decreases, and in women, on the contrary, increases, which is most likely due to the level of estrogens in the body [4].Objective: to evaluate the effect of estradiol on the expression of PSCK9 in patients with IHD Materials and methods: 39 men (average age 60.95±5.89 years) participated in the study IHD sufferers from a group of very high cardiovascular risk. Prior to the start of the study, for 8 weeks, all patients took a combination of the maximum tolerated dose of HMG-CoA Reductase inhibitor (Atorvastatin 80mg 1p / day) with an inhibitor of intestinal cholesterol absorption (Ezetemib) and did not reach the target values of LDL cholesterol < 1.4 mmol. After that, Alirocumab 150mg 1 injection per 14 days was added to the treatment (PRALUENT, SANOFI, France), followed by monitoring of LDL cholesterol and estradiol levels every 4 weeks. The median of the study was months. The program SPSS 23.0 (IBM USA) was used for statistical data processing.Results: at the start of the study, the average LDL cholesterol level was 2.28±0.08 mmol, the estradiol level was 149.13±87.3 pg/ml. A large variation in estradiol indicators (standard deviation) was associated with individual characteristics of the endocrine status of men. The use of Alirocumab showed high statistical significance after 4 weeks of using the drug (2 injections), the level of LDL cholesterol decreased by 34.2% and amounted to 1.5±0.1 mmol (p<0.001), the level of estradiol in the same control increased by 8.39% and did not show statistical significance (p=0.64). After 6 months of treatment, the LDL cholesterol level decreased by 43.86% 1.28±0.14 mmol (p<0.001), the estradiol level increased by 15.15% after 6 months of treatment (p=0.47). At the end of the study, after 12 months of treatment with PCSK9 inhibitors, the level of LDL cholesterol decreased by 49.56% from the baseline level and amounted to 1.15±0.15 mmol (p<0.001); the target values of LDL cholesterol reached 97.43% of patients (n=38). The estradiol level after 12 months of treatment with PCSK9 inhibitors was 162.64±86.14 pg/ml, increased by 19.37% from the baseline values and showed no statistical significance (p=0.39). In the correlation analysis, no significant relationship was found between the dynamics of LDL cholesterol reduction and an increase in estradiol levels.Conclusions: the revealed features of changes in endogenous risk factors in patients with coronary heart disease expand modern ideas about the role of PCSK9 inhibitors in the context of correction of atherogenic lipoprotein fractions.

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About the authors

Andrew Kuznetsov

"Moscow Regional Hospital of Prof. Rozanova V.N.", Moscow region, Russia; Kursk State Medical University, Ministry of Health of the Russian Federation, Kursk, Russia

Author for correspondence.
Email: dr.cardiologist.kuznetsov@yandex.ru
ORCID iD: 0000-0001-6290-1195
SPIN-code: 2967-7590

Врач- кардиолог, отделение кардиологии

Russian Federation, Russia, Moscow region, Pushkino, Aviatsionnaya str., 35

References

  1. A global brief on hypertension. Silent killer, global public health crisis. World Health Organization. 2013. Available at: https://www.who. int/cardiovascular_diseases/publications/global_brief_hypertension/en (date of access – 10.02.2022).
  2. Seidah N.G., Benjannet S., Wickham L. et al. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc Natl Acad Sci U S A. 2003; 100(3): 928–33. doi: 10.1073/pnas.0335507100.
  3. Lakoski SG, Lagace TA, Cohen JC, Horton JD, Hobbs HH. Genetic and metabolic determinants of plasma PCSK9 levels. J Clin Endocrinol Metab. 2009;94:2537–43.
  4. Baass A, Dubuc G, Tremblay M, Delvin EE, O’Loughlin J, Levy E, Davignon J, Lambert M. Plasma PCSK9 is associated with age, sex, and multi ple metabolic markers in a population-based sample of children and adolescents. Clin Chem. 2009;55:1637–45

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