Endothelium Protective Function of Statins in Men and Women with Coronary Atherosclerosis
https://doi.org/10.20996/1819-6446-2016-12-5-503-508
Abstract
Aim. To study the relationship between serum endothelin levels and lipid-lowering therapy in patients with confirmed coronary atherosclerosis.
Material and methods. Patients (n=447; 320 men and 127 women; mean age 62.7±8.8 years) with coronary atherosclerosis, confirmed by coronary angiography, were included into the study. Serum endothelin levels were assessed by enzyme immunoassay (ELISA).
Results. Negative correlation between the statins receiving and serum endothelin level was found in men (r=-0.11; p=0.04). Serum endothelin level was 1.8 times lower in men who received statins, compared with men without statin therapy. The relationship between statins receiving and serum endothelin level was not found in women with coronary atherosclerosis.
Conclusion. The statins receiving in men with coronary atherosclerosis, in contrast to women, negatively correlated with serum endothelin level and is associated with its almost twofold reduction. Relationship between serum endothelin level and receiving other drugs was not found.
About the Authors
M. V. KlimushinaRussian Federation
PhD, Senior Researcher, Department of Study of Biochemical Risk Markers of Chronic Non-Communicable Diseases, State Research Centre for Preventive Medicine
N. G. Gumanova
Russian Federation
PhD, Leading Researcher, Department of Study of Biochemical Risk Markers of Chronic Non-Communicable Diseases, State Research Centre for Preventive Medicine
A. Ju. Gorshkov
Russian Federation
MD, Graduate Student, Department of Clinical Cardiology and Molecular Genetics, State Research Centre for Preventive Medicine
N. E. Gavrilova
Russian Federation
MD, PhD, Senior Researcher, Department of Clinical Cardiology and Molecular Genetics, State Research Centre for Preventive Medicine
V. A. Metel'skaja
Russian Federation
PhD, Professor, Head of Department of Study of Biochemical Risk Markers of Chronic Non-Communicable Diseases, State Research Centre for Preventive Medicine
S. A. Boytsov
Russian Federation
MD, PhD, Professor, Head of State Research Centre for Preventive Medicine
References
1. Mudau M., Genis A., Lochner A., et al. Endothelial dysfunction – the early predictor of atherosclerosis. Cardiovasc J Afr 2012;23(4):222-31.
2. Deanfield J.E., Halcox J.P., Rabelink T.J. Endothelial function and dysfunction: testing and clinical relevance. Circulation 2007;115:1285-95.
3. Davenport A.P., Hyndman K.A., Dhaun N., et al. Endothelin. Pharmacol Rev 2016;68:357-418.
4. Doggrell S.A. The endothelin system and its role in acute myocardial infarction. Expert Opin Ther Targets 2004;8(3):191-201.
5. Gottlieb S.S., Harris K., Todd J., et al. Prognostic significance of active and modified forms of endothelin 1 in patients with heart failure with reduced ejection fraction. Clin Biochem 2015;48(4-5):292-6.
6. Sainani G.S., Maru V.G., Mehra A.P. Role of endothelin-1 in genesis of coronary artery disease. Indian Heart J 2005;57(2):121-7.
7. Bossard M., Pumpol K., van der Lely S., et al. Plasma endothelin-1 and cardiovascular risk among young and healthy adults. Atherosclerosis 2015;239(1):186-91.
8. Hirata Y., Nagata D., Suzuki E., et al. Diagnosis and treatment of endothelial dysfunction in cardiovascular disease. Int Heart J 2010;51(1):1-6.
9. RadenkovićM., StojanovićM., Potpara T. et al. Therapeutic Approach in the Improvement of Endothelial Dysfunction: The Current State of the Art. Biomed Res Int 2013;2013:252158.
10. Nicholls S.J., Ballantyne C.M., Barter P.J., et al. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med 2011;365:2078-87.
11. Miller P.E., Martin S.S. Approach to Statin Use in 2016: an Update. Curr Atheroscler Rep 2016;18(5):20.
12. Souza-Costa D.C., Sandrim V.C., Lopes L.F., et al. Anti-inflammatory effects of atorvastatin: modulation by the T-786C polymorphism in the endothelial nitric oxide synthase gene. Atherosclerosis 2007;193(2):438-44.
13. Hosokawa S., Hiasa Y., Tomokane T., et al. The effects of atorvastatin on coronary endothelial function in patients with recent myocardial infarction. Clin Cardiol 2006;29(8):357-62.
14. Ridker P.M., Cannon C.P., Morrow D., et al. Pravastatin or Atorvastatin Evaluation and Infection Therapy- Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) Investigators. C-reactive protein levels and outcomes after statin therapy. N Engl J Med 2005;352(1):20-8.
15. Liao J.K. and Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 2005;45: 89-118.
16. Puccetti L., Pasqui A.L., Pastorelli M.,Bova G., et al. Time-dependent effect of statins on platelet function in hypercholesterolaemia. Eur J Clin Invest 2002;32(12):901-8.
17. Ito T., Ikeda U., Shimpo M., et al. HMG-CoA reductase inhibitors reduce interleukin-6 synthesis in human vascular smooth muscle cells. Cardiovasc Drugs Ther 2002;16(2):121-6.
18. Eberlein M., Heusinger-Ribeiro J., Goppelt-Struebe M. Rho-dependent inhibition of the induction of connective tissue growth factor (CTGF) by HMG CoA reductase inhibitors (statins). Br J Pharmacol 2001;133(7):1172-80.
19. Plenge J.K., Hernandez T. L., Weil K.M., et al. Simvastatin Lowers C-Reactive Protein Within 14 Days An Effect Independent of Low-Density Lipoprotein Cholesterol Reduction. Circulation 2002;106:1447- 52.
20. Muraca M., Baggio G., Miconi L., et al. Acute effects of HMG-CoA reductase inhibitors on biliary lipids in patients with interrupted enterohepatic circulation. Eur J Clin Invest 1991;21(2):204-8.
21. Sahebkar A., Kotani K., Serban C., et al. Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group. Statin therapy reduces plasma endothelin-1 concentrations: A meta-analysis of 15 randomized controlled trials. Atherosclerosis 2015;241(2):433-42.
22. Schachter M. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam Clin Pharmacol 2005;19:117-25.
23. Hernández-Perera O., Pérez-Sala D., Navarro-Antolín J., et al. Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells. J Clin Invest 1998;101(12):2711-9.
24. Tsunekawa T., Hayashi T., Kano H., et al. Cerivastatin, a hydroxymethylglutaryl coenzyme a reductase inhibitor, improves endothelial function in elderly diabetic patients within 3 days. Circulation 2001;104(4):376-9.
25. Polderman K.H., Stehouwer C.D., van Kamp GJ, et al. Influence of sex hormones on plasma endothelin levels. Ann Intern Med 1993;118(6):429-32.
26. Schooling C.M., Au Yeung S.L., Freeman G., et al. The effect of statins on testosterone in men and women, a systematic review and meta-analysis of randomized controlled trials. BMC Med 2013;11:57.
Review
For citations:
Klimushina M.V., Gumanova N.G., Gorshkov A.J., Gavrilova N.E., Metel'skaja V.A., Boytsov S.A. Endothelium Protective Function of Statins in Men and Women with Coronary Atherosclerosis. Rational Pharmacotherapy in Cardiology. 2016;12(5):503-508. (In Russ.) https://doi.org/10.20996/1819-6446-2016-12-5-503-508