Variability of arterial pressure and cardiac rhythm in patients with coronary heart disease and diabetes mellitus: Effect of sodium-glucose co-transporter 2 inhibitor

Abstract

Introduction: A factor that worsens the course of coronary heart disease (CHD) in patients with type 2 diabetes mellitus (DM2) is cardiovascular autonomic neuropathy (CAN), in which the risk of sudden death increases fivefold. The prevalence of CAN in patients with both CHD and DM2 may reach 60%. Classic cardiovascular tests (CCT) do not permit identification of CAN at the preclinical stage. A modern method of treatment for DM2 uses sodium-glucose co-transporter 2 inhibitors, which have confirmed cardioprotective effects.

Aim: To analyze the prevalence of alterations of arterial pressure variability (APV) and of heart rhythm variability (HRV) in patients with both CHD and DM2 and the effect of empagliflozin on these parameters.

Materials and methods: A total of 210 patients aged 64.5 ± 6.7 years (103 men) with both CHD and DM2 were examined (group1). Anthropometric and biochemical parameters were analyzed, electrocardiogram and arterial pressure were monitored daily, and CCT was performed. For comparison, 64 patients with CHD with no alterations in the carbohydrate metabolism were examined (group2, n=64, aged 66.4 ± 2.3 years). Further, among patients in group1, patients with impaired HRV and APV were selected, but they had CCT scores < 4.0, and they were divided into group1G (n=22) where empagliflozin was added (10–25 mg/day) and group1C (n=20) where the previous therapy was continued.

Results:  CAN was detected in 22% of patients with CHD and DM2, and all patients had impaired HRV and ADV. Deviations of HRV and APV parameters with normal CCT scores (< 4.0) were detected in 43% of the patients. Within 6 months of treatment with empagliflozin, the HbA1c level decreased from 8.38% ± 0.56% to 6.9% ± 0.26% (p< 0.05); in the groupwithout empagliflozin treatment, it decreased from 8.28% ± 0.32% to 7.30% ± 0.29% (p< 0.05). In the empagliflozin group, the average heart rate per day decreased from 86.7 ± 2.4 to 76.7 ± 2.1 beats/min (p< 0.05), the circadian index increased from 1.19 ± 0.02 to 1.30 ± 0.01 (p< 0.05), the SDNN increased from 106.1 ± 2.21 to 114.03 ± 2.34 ms (p< 0.05), and the systolic arterial pressure variability index decreased from 22.9% ± 1.7% to 16.4% ± 1.9% at daytime (p< 0.05) and from 16.8% ± 2.2% to 12.3% ± 2.6% at nighttime (p< 0.05).

Conclusion: The identified alterations of HRV and APV parameters may be manifestations of CAN, and CCT score < 4.0 may indicate the preclinical stage. Positive dynamics of HRV and APV was recorded with empagliflozin therapy, which improved the functional condition of the autonomic nervous system.

Keywords

coronary heart disease / CHD / diabetes mellitus / autonomic neuropathy / heart rate variability / arterial pressure variability / empagliflozin

References

[1] The Demographic Yearbook of Russia. 2015. Statistical handbook / Rosstat. Moscow; 2015. (In Russ).

[2] Демографический ежегодник России. 2015: Статистический сборник / Росстат. M.; 2015.

[3] Vishnevskii KA, Zemchenkov AYu, Gerasimchuk RP, et al. Pharmacoeconomic of CKD-MBD Treatment: Literature Review. Nephrology. 2018;22(1):38–51. (In Russ). doi: 10.24884/1561-6274-2018-22-1-38-51

[4] Вишневский К.А., Земченков А.Ю., Герасимчук Р.П., и др. Фармакоэкономика лечения МКН-ХБП: обзор литературы // Нефрология. 2018. Т. 22, № 1. С. 38–51. doi: 10.24884/1561-6274-2018-22-1-38-51

[5] Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic he art failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal. 2016;37:2129–2200. doi: 10.1093/eurheartj/ehw128

[6] Ponikowski P., Voors A.A., Anker S.D., et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic he art failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC // European Heart Journal. 2016. Vol. 37. P. 2129–2200. doi: 10.1093/eurheartj/ehw128

[7] Roger LV, Go AS, Lloid–Jones DM, et al. Executive summary: heart disease and stroke statistics ― 2012 update: a report from the American Heart Association. Circulation. 2012;125(1):188–97. doi: 10.1161/CIR.0b013e3182456d46

[8] Roger L.V., Go A.S., Lloid–Jones D.M., et al. Executive summary: heart disease and stroke statistics ― 2012 update: a report from the American Heart Association. Circulation. 2012. Vol. 125, № 1. P. 188–197. doi: 10.1161/CIR.0b013e3182456d46

[9] Pappachan JM, Sebastian J, Bino BC, et al. Cardiac autonomic neuropathy in diabetes mellitus: prevalence, risk factors and utility of corrected QT interval in the ECG for its diagnosis. Postgraduate Medical Journal. 2008;84(990):205–10. doi: 10.1136/pgmj.2007.064048

[10] Pappachan J.M., Sebastian J., Bino B.C., et al. Cardiac autonomic neuropathy in diabetes mellitus: prevalence, risk factors and utility of corrected QT interval in the ECG for its diagnosis // Postgraduate Medical Journal. 2008. Vol. 84, № 990. P. 205–210. doi: 10.1136/pgmj.2007.064048

[11] Dedov II, Shestakova MV, Mayorov AYu, editors. Standards of specialized diabetes care. 9th ed. Moscow; 2019. (In Russ). doi: 10.14341/DM221S1

[12] Дедов И.И., Шестакова М.В., Майоров А.Ю., ред. Клинические рекомендации «Алгоритмы специализированной медицинской помощи больным сахарным диабетом» (9-й выпуск). М.; 2019. doi: 10.14341/DM221S1

[13] Boitsov SA, Samorodskaya IV. Mortality and lost years of life as a result of cardiovascular premature deaths. Cardiovascular Therapy and Prevention. 2014;13(2):4–11. (In Russ). doi: 10.15829/1728-8800-2014-2-4-11

[14] Бойцов С.А., Самородская И.В. Смертность и потерянные годы жизни в результате преждевременной смертности от болезней системы кровообращения // Кардиоваскулярная терапия и профилактика. 2014. Т. 13, № 2. С. 4–11. doi: 10.15829/1728-8800-2014-2-4-11

[15] Tkacheva ON, Vertkin AL. Diabeticheskaya avtonomnaya neyropatiya. Moscow: GEOTAR-Media; 2009. (In Russ).

[16] Ткачева О.Н., Верткин А.Л. Диабетическая автономная нейропатия. М.: ГЭОТАР-Медиа; 2009.

[17] Sharonova LA, Verbovoy AF. The place of gliflozins in the management of type 2 diabetes mellitus. Farmateka. 2019;26(4):105–10. (In Russ). doi: 10.18565/pharmateca.2019.4.105-110

[18] Шаронова Л.А., Вербовой А.Ф. Место глифлозинов в управлении сахарным диабетом 2 типа // Фарматека. 2019. Т. 26, № 4. С. 105–110. doi: 10.18565/pharmateca.2019.4.105-110

[19] Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. The New England Journal of Medicine. 2015;373(2):2117–28. doi: 10.1056/NEJMoa1504720

[20] Zinman B., Wanner C., Lachin J.M., et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes // The New England Journal of Medicine. 2015. Vol. 373, № 2. P. 2117–2128. doi: 10.1056/NEJMoa1504720

[21] Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. The New England Journal of Medicine. 2017;377(7):644–57. doi: 10.1056/NEJMoa1611925

[22] Neal B., Perkovic V., Mahaffey K.W., et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes // The New England Journal of Medicine. 2017. Vol. 377, № 7. P. 644–657. doi: 10.1056/NEJMoa1611925

[23] Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. The New England Journal of Medicine. 2019;380(4):347–57. doi: 10.1056/NEJMoa1812389

[24] Wiviott S.D., Raz I., Bonaca M.P., et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes // The New England Journal of Medicine. 2019. Vol. 380, № 4. P. 347–357. doi: 10.1056/NEJMoa1812389

[25] Rosenstock J., Frias J., Páll D., Charbonnel B., Pascu R., Saur D. et al. Effect of ertugliflozin on glucose control, body weight, blood pressure and bone density in type 2 diabetes mellitus inadequatelycontrolled on metformin monotherapy (VERTIS MET). Diabetes, Obesity & Metabolism. 2018;20(3):520–29. doi: 10.1111/dom.13103

[26] Rosenstock J., Frias J., Páll D., et al. Effect of ertugliflozin on glucose control, body weight, blood pressure and bone density in type 2 diabetes mellitus inadequatelycontrolled on metformin monotherapy (VERTIS MET) // Diabetes, Obesity & Metabolism. 2018. Vol. 20, № 3. P. 520–529. doi: 10.1111/dom.13103

[27] Bayevsky RM, Ivanov GG. Cardiac rhythm variability: the theoretical aspects and the opportunities of clinical application (lecture). Ultrasound and Functional Diagnostics. 2001;(3):106–27. (In Russ).

[28] Баевский P.M., Иванов Г.Г. Вариабельность сердечно го ритма: теоретические аспекты и возможности клинического применения // Ультразвуковая и функциональная диагностика. 2001. № 3. C. 108–127.