ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 7 of 41
УЖМБС 2017, 2(3): 36–42
Clinical Medicine

Efficiency Evaluation of the Combination Therapy for Comorbid Arterial Hypertension with Diabetes Mellitus 2 Type Depending on the Genetic Polymorphism of the Angiotensin-Converting Enzyme

Bilovol O., Bobronnikova L., Al-Trawneh O.

The aim of the article is to evaluate the efficiency of the combination antihypertensive therapy using treatment plan including lisinopril and carvedilol in patients with combined arterial hypertension and diabetes mellitus 2 type considering polymorphic marker option 2350 A/G gene angiotensin-converting enzyme. Materials and methods of the research. 58 patients having arterial hypertension stage II grade 2 and subcompensated diabetes mellitus 2 type were examined. The patients were grouped based on the polymorphism of genetic markers 2350 A/G gene of the angiotensin-converting enzyme. Group 1 (n = 13) patients with genotype A/A polymorphic marker 2350 A/G; group 2 (n = 45) with unfavorable genotype A/G and G/G polymorphic marker 2350 A/G. All patients received antihypertensive therapy with a combination of lisinopril and carvedilol. The patients received rosuvastatin 10 mg per day and acetylsalicylic acid of 75 mg daily dose. Moreover, all patients received hypoglycemic therapy using a combination of metformin and gliclazide. Before and after treatment blood pressure, body mass index, carbohydrate and lipid metabolism and structural-functional changes in the myocardium were evaluated. Results. In group with A/G and G/G variants of polymorphic marker 2350 A/G gene angiotensin-converting enzyme before treatment were significantly higher systolic blood pressure and diastolic blood pressure in comparison with the group of patients having genotype A/A (p<0,05). As a result of the therapy a significant decrease in blood pressure was observed in both groups (p<0.001). It should be noted that prior to treatment more pronounced disorders and structural-functional changes in the myocardium were observed in the group with A/G and G/G genotypes (p<0.05). After treatment the ejection fraction values tended to increase in the A/A genotype group, and a significant increase in patients with unfavorable genotypes (p<0.05) was noticed. In both groups, there was a significant volume decrease in the atria and the diameter of the aorta (p<0.05). There was a significant decrease in total cholesterol, triglycerides, low density lipoprotein cholesterol, having statistically significant increase in high density lipoprotein cholesterol (p<0,05) in patients of the groups 1 and 2 after treatment. Changes in carbohydrate profile after treatment established significant reduction in fasting blood glucose levels as in patients with genotype A/A, as genotypes A/G and G/G (p<0,05). Conclusions: It was found out that the genotype A/G and G/G polymorphic marker 2350 A/G gene angiotensin-converting enzyme in patients with arterial hypertension and diabetes mellitus 2 type associated with higher numbers of blood pressure, more pronounced myocardial hypertrophy and metabolic disorders than in patients with A/A genotype. Antihypertensive therapy with the inclusion of lisinopril and carvedilol showed its efficiency in both groups of patients. There was a significant decrease in blood pressure, improvement of the structural-functional parameters of the myocardium as well as the parameters of carbohydrate and lipid metabolism.

Keywords: arterial hypertension, diabetes mellitus type 2, antihypertensive therapy, genetic polymorphism

Full text: PDF (Ukr) 225K

  1. Bella JN, Goring HH. Genetic epidemiology of left ventricular hypertrophy. American Journal of Cardiovascular Drugs. 2012; 2: 267–78.
  2. Ebrahim S, Taylor F, Brindle P. Statins for the primary prevention of cardiovascular disease. BMJ. 2014; 348: 280.
  3. Gillespie CD, Hurvitz KA. Prevalence of hypertension and controlled hypertension-United States, 2007-2010. Morbidity and Mortality Weekly Report. 2013; 62: 144–8.
  4. Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AN, Tsapas A, Wender R, Matthews DR. Management of Hyperglycemia in Type 2 Diabetes, 2015: a patient-centered approach update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015; 38 (1): 140–9.
  5. Marques G, Krieger JE, Casarini DE. Angiotensin-converting enzyme: a possible genetic marker of hypertension. Hypertension. 2002; 20 (suppl 4): 263.
  6. Mehta PK, Griendling KK. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physil. 2007; 292 (1): 82–97.
  7. Niu WQ, Qi Y, Gao PJ. Review: association between angiotensin converting enzyme G2350A polymorphism and hypertension risk a meta-analysis. J Renin Angiotensin Aldosterone Syst. 2011; 12: 8-14.
  8. Pan M, Zhu J-H, Liu Z-H, Jiang W-P, Cui Z-C, Yu X-H, Li H-M, Yang X-J. Angiotensin-converting enzymegene 2350 G/A polymorphism is associated with left ventricular hypertrophy but not essential hypertension. Hypertension Research. 2007; 30: 31–7.
  9. Sahn DY, Gur M, Elbansan Z, Kalkan GY, Ozdogru I, Kivrak A, Gozubuyuk G, Kuloğlu O, Sümbül Z, Çayli M. Myocardial performance index and aortic dispensability in patients with different left ventricular geometry in newly diagnosed essential hypertension. Blood Press. 2013; 22: 329–35.
  10. Santulli G, Trimarco B, Iaccarino G. G-protein-coupled receptor kinase 2 and hypertension: molecular insights and pathophysiological mechanisms. High Blood Press Cardiovasc Prev. 2013; 20: 5–12.
  11. Saeed M, Siddiqui S, Khan A, Zahid A, Hasan S. Philippe M. Association of angiotensin converting enzyme gene polymorphisms with left ventricular hypertrophy. Neuroendocrinol Lett. 2005; 26 (4): 393–6.
  12. Uehara Y, Miura S-I, Yahiro E, Saku K. Non - ACE pathway-induced angiotensin II production. Curr Pharm. 2013; 19: 3054–9.
  13. Zhong-Bao R, Jian-Min L, Li Z. Relationship of ACE 2350 G/A and chymase genetic polymorphisms with left ventricular hypertrophy in Chinese essential hypertension patients. Int J Clin Exp Pathol. 2016; 9 (1): 237–43.