2015


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2015/№1

Polymorphism of genes, associated with increased cardiovascular risk, and cognitive disorders in patients with ischemic heart disease complicated with chronic heart failure

Martynovich T. V.1, Akimova N. S.1, Fedotov E. A.2, Shvarts Yu. G.1
1 – State Budgetary Educational Institution of Higher Professional Education, “V. I. Razumovsky Saratov State Medical University” at the RF Ministry of Health Care, Bolshaya Kazachjya 112, Saratov 410012
2 – Limited Liability Society “Medical Di Center”, Moskovskaya 23, Saratov 410000

Keywords: CAD, cognitive abnormality, gene polymorphism, cardiovascular risk, CHF

DOI: 10.18087/rhj.2015.1.2021

Background. Chronic heart failure (CHF) results in disorders of cerebral circulation, thereby facilitating development of cognitive deficit. Understanding clinical and prognostic significance of gene polymorphism associated with increased cardiovascular risk during CHF development and progression is still incomplete. Furthermore, evaluating the contribution of gene polymorphism to development of cognitive dysfunction has not been performed for this patient contingent. Aim. To study the effect of gene polymorphism associated with increased cardiovascular risk on features of the CHF course and cognitive dysfunction in patients with IHD. Materials and methods. Cognitive tests, nuclear magnetic resonance tomography (NMRT), duplex scanning of brachycephalic arteries, Doppler-EchoCG, determination of ADRB2, AGT and NOS3 gene polymorphism, and measurements of lipids, homocysteine and brain natriuretic peptide (BNP) were performed for 40 patients with FC II–IV CHF of ischemic origin. Results were analyzed using the STATISTICA-7.0 software. Results. We found correlations of polymorphous variants of ADRB2, AGT and NOS3 genes with morphological changes in the brain and results of cognitive tests. Presence of the G allele in the ADRB2 gene (G516R G>A polymorphism), the T allele in the AGT gene (T174M C>T polymorphism), and the С allele in the AGT gene (M235T T>C polymorphism) was associated with worsening of cognitive test results. Presence of the T allele in the NOS3 gene (D298E G>T polymorphism) was associated with reduced thickness of gray matter (GM) in parietal and temporal lobes, and decreased diffusion coefficients of water molecules in GM of frontal and parietal lobes. In addition, the presence of risk alleles in ADRB2 and AGT genes was associated with reduced diameter and increased intima-media thickness (IMT) in carotid arteries. Statistically significant correlations of ADRB2, AGT and NOS3 gene polymorphism and CHF clinico-laboratory characteristics were not observed. Conclusion. ADRB2, AGT and NOS3 gene polymorphisms statistically significantly correlated with cognitive functions and status of brain GM as well as with atherosclerosis indices in patients with CHF of ischemic origin.
  1. McMurray JJ, Adamopoulos S, Anker SD et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 of the European society of cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012 Jul;33 (14):1787–847.
  2. Акимова Н. С., Персашвили Д. Г., Мартынович Т. В., Шварц Ю. Г. Когнитивные расстройства и состояние серого вещества головного мозга при ХСН на фоне ИБС. Журнал Сердечная Недостаточность. 2011;12 (5):282–5.
  3. Морозова Т. Е., Рыкова С. М. Сердечно-сосудистые заболевания и когнитивные нарушения. Consilium medicum. 2010;12 (9):85–9.
  4. Мареев В. Ю., Даниелян М. О., Беленков Ю. Н. Сравнительная характеристика больных с ХСН в зависимости от величины ФВ по результатам Российского многоцентрового исследования ЭПОХА–О–ХСН: снова о проблеме ХСН с сохранной систолической функцией левого желудочка. Журнал Сердечная Недостаточность. 2006;7 (4):164–71.
  5. Cleland JGF, Cohen-Solal A, Cosin Aguilar J et al. Increasing awareness and improving the management of heart failure in Europe: the IMPROVEMENT of HF initiative. Eur J Heart Fail. 1999 Jun 1;1 (2):139–44.
  6. Национальные рекомендации ВНОК и ОССН по диагностике и лечению ХСН (третий пересмотр). Журнал Сердечная Недостаточность. 2010;11 (1):3–62.
  7. Andreassi MG, Adlerstein D, Carpeggiani C et al. Individual and summed effects of high-risk genetic polymorphisms on recurrent cardiovascular events following ischemic heart disease. Atherosclerosis. 2012 Aug;223 (2):409–15.
  8. Pereira SB, Velloso MW, Chermont S et al. B-adrenergic receptor polymorphisms in susceptibility, response to treatment and prognosis in heart failure: Implication of ethnicity. Mol Med Rep. 2013 Jan;7 (1):259–65.
  9. Fatini C, Abbate R, Pepe G et al. Searching for a better assessment of the individual coronary risk profile: the role of angiotensin-converting enzyme, angiotensin II type 1 receptor and angiotensinogen gene polymorphisms. Eur Heart J. 2000 Apr;21 (8):633–8.
  10. Дорофеева Н. П., Кастанаян А. А., Шлык С. В. и др. Полимор­физм генов ренин-ангиотензиновой системы у больных артериальной гипертензией и ишемической болезнью сердца, осложненной хронической сердечной недостаточностью. Журнал Артериальная гипертензия. 2005;11 (4):235–8.
  11. Кириченко П. Ю. Роль гемодинамических, конституционных и генетических факторов в формировании хронической недостаточности кровообращения. Автореф. дис…. канд. мед. наук. – СПб., 2001. – 137с.
  12. Бабак О. Я., Кравченко Н. А. Роль ренин-ангиотензиновой системы в ремоделировании сердца и сосудов. Украинский терапевтический журнал. 2005;2:89–96.
  13. Bai Y, Wang L, Hu S, Wei Y. Association of angiotensin-converting enzyme I / D polymorphism with heart failure: a meta-analysis. Mol Cell Biochem. 2012 Feb;361 (1-2):297–304.
  14. Wang YJ, Pan Y. Angiotensinogen gene M235T polymorphism and risk of coronary artery disease: a meta-analysis. Mol Med Rep. 2012 Oct;6 (4):884–8.
  15. Levinsson A, Olin AC, Bjцrck L at al. Nitric oxide synthase (NOS) single nucleotide polymorphisms are associated with coronary heart disease and hypertension in the INTERGENE study. Nitric Oxide. 2014 May 30;39 (1):1–7.
  16. Mehri S, Mahjoub S, Farhati A et al. Angiotensinogen gene polymorphism in acute myocardial infarction patients. J Renin Angiotensin Aldosterone Syst. 2011 Mar;12 (1):42–7.
  17. Багмет А. Д., Шестопал Н. С. I / D-полиморфизм гена ангиотензинпревращающего фермента, морфофункциональное состояние сердца и суточный профиль артериального давления у молодых мужчин с артериальной гипертонией. Терапевтический архив. 2005;77 (9):16–20.
  18. Целуйко В. И., Пелецкая О. В. Влияние типа I / D полиморфизма гена ангиотензинпревращающего фермента на клиническое течение гипертонической болезни. Украинский кардиологический журнал. 2008;2:33–7.
  19. Xin Y, Song X, Xue H et al. A common variant of eNOS gene (E298I) is an independent risk factor for left ventricular hypertrophy in human essential hypertension. Clin Sci. 2009;117 (2):67–73.
  20. Xu MQ, Ye Z, Hu FB, He L. Quantitative assessment of the effect of angiotensinogen gene polymorphisms on the risk of coronary heart disease. Circulation. 2007 Sep;116 (12):1356–66.
  21. Wang WZ. Association between T174M polymorphism in the angio­tensinogen gene and risk of coronary artery disease: a meta-analysis. J Geriatr Cardiol. 2013 Mar;10 (1):59–65.
  22. Liggett SB, Wagoner LE, Craft LL et al. The Ile164 beta2‑adrenergic receptor polymorphism adversely affects the outcome of congestive heart failure. J Clin Invest. 1998 Oct 15;102 (8):1534–9.
  23. Шмырев В. И., Миронов Н. В., Мкртчян Н. С. и др. Энер­гети­ческий обмен головного мозга и его исследование с помощью позитронно-эмиссионной томографии. Журнал Кремлевская медицина. Клинический вестник. 2006;1:7–9.
  24. Ивлева А. Я. Различия фармакологических свойств бета-адреноблокаторов и их клиническое значение. Consilium Medicum. 2003;5 (11):8–12.
  25. Hingorani AD. Endothelial nitric oxide synthase polymorphisms and hypertension. Curr Hypertens Rep. 2003 Feb;5 (1):19–25.
Martynovich T. V., Akimova N. S., Fedotov E. A. et al. Polymorphism of genes, associated with increased cardiovascular risk, and cognitive disorders in patients with ischemic heart disease complicated with chronic heart failure. Russian Heart Journal. 2015;14 (1):13–18

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