Lviv clinical bulletin 2016, 4(16): 8-14

https://doi.org/10.25040/lkv2016.04.008

The Peculiarities of the Endothelial Function, Blood Lipid Spectrum and Heart Rate Variability in Patients with Stable Angina, Depending on the Heart Rate Frequency

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Z. Bilous, О. Аbrahamovych

Danylo Halytsky Lviv National Medical University

The survey studies the impact of heart rate on the development of endothelial dysfunction and disorders of heart rate variability in patients with stable angina.

Introduction. Endothelium plays an important role in the adaptation of coronary blood flow to myocardial oxygen demand in case of angina pectoris. In case of damage there is an imbalance between the level of endothelium synthesized substances – imbalance between vasodilators and vasoconstrictors towards increased synthesis of vasoconstrictors, which plays a signifi  cant role in causing stenosis of coronary arteries, affected by atherosclerosis. The loss of endothelial anti-inflammatory, antioxidant and antithrombotic capacity causes disorders of perfusion, tissue hypoxia. Episodes of transient coronary artery vasoconstriction deepen inadequate coronary blood flow, further limiting it. Increased heart rate mechanically damages the vascular wall, causing endothelial dysfunction. High heart rate can affect hemostasis, promote destabilization and rupture of an atherosclerotic plaque.

Purpose of the study. To evaluate the peculiarities of the endothelial function, blood lipid spectrum and heart rate variability in patients with stable angina, depending on the heart rate frequency.

Materials and research methods. The study involved 125 patients with stable angina, which were divided into groups, depending on the magnitude of heart rate. The control group consisted of 34 practically healthy persons  surveyed comparable according to age and sex.

The average heart rate in patients of groups 1, 2 and 3 was, on average, 89.9 ± 6.57 bpm, 70.26 ± 4.37 bpm and 58,0 ± 1,12 bpm respectively, in the control group – 70.7 ± 5.4 bpm (p1.4 < 0.05, p2,4 > 0.05, p3,4 < 0.05).

Serum ELISA determined endothelin-1; method for determining the activity of vWF is based on its ability to induce platelet aggregation in the presence of aggregation inducer ristozitine; the study of blood lipid spectrum was carried out by using spectrophotometric method; studying heart rate variability, we analysed the temporal and spectral characteristics. Statistical analysis of the results of research was carried out by the variation statistics method using Statistica 6.0 and Microsoft Offi  ce Excel 2007.

Results of the investigation and their discussion. In patients with stable angina endothelial dysfunction was pronounced. In patients with stable angina with a heart rate >80 bpm endothelial dysfunction was more pronounced (increased content of endothelin-1 – 5.85 ± 0.31 fmol/ml (р1,2 < 0.01, р1,3 < 0.01) and von Willebrand factor – 186.3 ± 11.0 % (р1,2 < 0.01, р1,3 < 0.01), and more significant pro-atherogenic changes of blood lipid spectrum (increased LDL-C, TG). Between HR end E-1, vW direct relationship.

LDL-Cin 1 group 4.27 ± 0.34 mmol/l and 4.12 ± 0.18 and 3.04 ± 0.25 mmol/lin 2 and 3 (р1,2 > 0.05, р1,3 < 0.01). TGin 1 group 2.19 ± 0.08 mmol/l, in 2 group – 1.98 ± 0.06, and in 1 group – 1.90 ± 0.04 (р1,2 < 0.05, р1,3 < 0.01). In patients with stable angina pro-atherogenic changes in lipid spectrum was pronounced. Between HR, LDL-C and TG established a direct relationship.

Based on the study of spectral and temporal characteristics of heart rate variability there was found an autonomic imbalance in these patients with a predominance of sympathetic nervous system activity. Between HR and heart rate variability the temporal and spectral characteristics direct relationship.

In patients with a heart rate of 60-80 and <60 beats per min. endothelial dysfunction was less pronounced, however, decrease of the level of parasympathetic ANS impact in the regulation of cardiac activity was found. Platelets and index of aggregation does not indicate the existence of substantial differences in surveyed groups.

Conclusions. Patients with stable angina have features of endothelial function, lipid spectrum of the blood and heart rate variability depending on heart rate, which are in the most significant signs of endothelial dysfunction, violation of lipid spectrum of the blood and the imbalance of autonomic nervous system dominated symptomatic level in patients with the frequency of heart rate over 80 beats / minute, and it can be used as a criterion for assessing the severity of the pathogenic mechanisms of stable angina.

References

  1. Aird WC. Endothelium in health and disease. Pharmacol Rep. 2008;60:139-143.
  2. DiFrancesco D, Camm A. Heart rate lowering by specific and selective if current inhibition with ivabradin. Drugs, 2004;64(16 Issue):1757-1765.
  3. DiFrancesco D. If-current inhibitors: properties of drug channel interaction. In : Selective and Specific If channel Inhibition in Cardiology. Science Press Ltd, 2004;(1). p. 1-13.
  4. Durand E, Scoazec A, Lafont A, Boddaert J, Al Hajzen A, Addad F et al. In vivo induction of endothelial apoptosis leads to vessel thrombosis and endothelial denudation. Circulation. 2004;109(21):2503-2506. https://doi.org/10.1161/01.CIR.0000130172.62481.90
  5. Mohácsi A, Magyar J, Tamás B, Nánási PP. Effects of endothelins on cardiac and vascular cells: new therapeutic target for the future? Curr Vasc Pharmacol. 2004;2(1):53-63. https://doi.org/10.2174/1570161043476528
  6. Lang CC, Gupta S, Kalra P, Keavney B, Menown I, Morley C et al. Elevated heart rate and cardiovascular outcomes in patients with coronary artery disease: clinical evidence and pathophysiological mechanisms. Atherosclerosis. 2010;212(1):1-8. https://doi.org/10.1016/j.atherosclerosis.2010.01.029
  7. Endemann DH, Schiffrin EL. Endothelial dysfunction. J Am Soc Nephrol. 2004;15(8):1983-1992. https://doi.org/10.1097/01.ASN.0000132474.50966.DA
  8. Esper RJ, Nordaby RA, Vilari-o JO, Paragano A, Cacharrón JL, Machado RA. Endotelial dysfunction: a comprehensive appraisal. Cardiovasc Diabetol. 2006;5:4. https://doi.org/10.1186/1475-2840-5-4
  9. Fox K, Borer JS, Camm AJ, Danchin N, Ferrari R, Lopez Sendon JL et al. Resting heart rate in cardiovascular disease. J Am Coll Cardiol. 2007;50(9):823-830. https://doi.org/10.1016/j.jacc.2007.04.079
  10. Benetos A, editor. Heart rate managemen. Wolters Kluwer Health, 2007. 88 p.
  11. Malik M, Bigger J T, Camm AJ, Kleiger RE, Malliani A, Moss AJ et al. Heart rate variability: Standards of measurement, physiological interpretation and clinical use. Taske force of the European society of cardiology and the North American society of pacing and electrophysiology (membership of the task force listed in the appendix). Eur Heart J. 1996;17(3):354-381. https://doi.org/10.1093/oxfordjournals.eurheartj.a014868
  12. Jouven X, Empana JP, Schwartz PJ, Desnos M, Courbon D, Ducimetière P. Heart-rate profile during exercise as a prediсtor of sudden death. N Engl J Med. 2005;352(19):1951-1958. https://doi.org/10.1056/NEJMoa043012
  13. Ker JA. Resting heart rate and cardiovascular events: risk factor or risk marker? S Afr Fam Pract. 2010;52(2):128-129. https://doi.org/10.1080/20786204.2010.10873951
  14. Landmesser U, Hornic B, Drexler H. Endothelial function: a critical determinant in atherosclerosis? Circulation. 2004;109(21 Suppl 1):27-33. https://doi.org/10.1161/01.CIR.0000129501.88485.1f
  15. Lanza GA, Fox KА, Crea F. Heart rate: a risk factor cardiac disease and outcomes? Pathophysiology of cardiac disease and the potential role of heart rate slowing. Adv Cardiol. 2006;43:1-16.
  16. Lopez JA, Dong JF. Shear stress and role of high molecular weight von Willebrand factor multimers in thrombus formation. Blood Coagul Fibrinolysis. 2005;16(1 Suppl):11-16. https://doi.org/10.1097/01.mbc.0000167657.85143.ad
  17. Lopez-Bescos L. Long-term safety and antianginal efficacy of he If-current inhibitor ivabradin in patients with chronic stable angina. Eur Heart J. 2004;25:876.
  18. Li YS, Haga JH, Chien S. Molecular basis of the effects of shear stress on vascular endothelial cells. J Biomech. 2005;38(10):1949-1971. https://doi.org/10.1016/j.jbiomech.2004.09.030
  19. Münzel T, Sinning C, Post F, Warnholtz A, Schulz E. Pathophysiology, diagnosis and prognostic implication of endothelial dysfunction. Ann Med. 2008;40(3):180-196. https://doi.org/10.1080/07853890701854702
  20. Preda I, Bencze J, Vargova K. Endothelial function and ischemic heart disease. Orvosi Hetilap. 2005;146(20 Suppl 2):1047-1053.
  21. Hozawa A, Ohkubo T, Kikuya M, Ugajin T, Yamaguchi J, Asayama K et al. Prodgnostic value of home heart rate for cardiovascular mortality in the general population: the Ohasama study. Am J Hypertension. 2004;17(11 Pt 1):1005-1010. https://doi.org/10.1016/S0895-7061(04)00897-0
  22. Fox K, Ferrari R, Tendera M, Steg PG, Ford I. Rationale and design of a randomized, double-blind, placebo-controlled trial of ivabradine in patients with stable coronary artery disease and left ventricular systolic dysfunction: the morBidity-mortality EvAlUaTion of the I (f) inhibitor ivabradine in patients with coronary disease and left ventricULar dysfunction (BEAUTIFUL) study. Am Heart J. 2006;152(5):860-866. https://doi.org/10.1016/j.ahj.2006.01.013
  23. Jouven X, Empana JP, Buyck JF, Canoui-Poitrine F, Kane A, Mouries C et al. Resting heart rate and its changes over years as a risk factor for mortality in the general population: the Paris Prospective Study I. (Abstract). Eur Heart J. 2006;27(1 Suppl):303.
  24. Tanowitz HB, Huang H, Jelicks LA, Chandra M, Loredo ML, Weiss LM et al. Role of endothelin 1 in the pathogenesis of chronic chagasic heart disease. Infect Immun. 2005;73(4):2496-2503. https://doi.org/10.1128/IAI.73.4.2496-2503.2005
  25. Sztajzel J. Heart rate variability: a noninvasive electrocardiographic method to measure the autonomic nervous system. Swiss Med Wkly. 2004;35:514-522.
  26. Tardif JC, Ford I, Tendera M, Bourassa MG, Fox K. Efficacy of ivabradine, a new selective If inhibitor, compared with atenolol in patients with chronic stable angina. Eur Heart J. 2005;26(23):2529-2536. https://doi.org/10.1093/eurheartj/ehi586
  27. Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F et al. Guidelines on the management of stable angina pectoris: executive summary: the Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. Eur Heart J. 2006;27(11):1341-1381. https://doi.org/10.1093/eurheartj/ehl001