Effects of fluvastatin, valsartan, and their combination on endothelial function in patients with arterial hypertension and dyslipidemia
Abstract
Aim. To study the effects of an angiotensin II receptor antagonist (ARA II) valsartan, a statin (fluvastatin XL), and their combination on endothelial function (EF) in patients with arterial hypertension (AH) and dyslipidemia (DLP).
Material and methods. In total, 30 patients with untreated, non-complicated Stage I-II AH and DLP IIA or IIB were randomised for 8-week monotherapy with valsartan or fluvastatin XL, with the subsequent addition of the second component, fluvastatin XL or valsartan, respectively.
Results. Valsartan monotherapy was associated with a reduced increase in linear blood flow velocity (LFV) during the reactive hyperemia test (RHT) - 177,7+5,8 vs. 170,0+4,9% (p<0,01). At the same time, brachial artery endothelium-dependent vasodilatation (BA EDVD) increased by 14% (p>0,05). Eight-week monotherapy with fluvastatin XL (80 mg/d) was linked to moderate but statistically significant reduction (-2%) in systolic blood pressure (SBP), with no effect on diastolic BP level. In RHT, LFV increase did not change, but EF improved, as manifested in BA EDVD increase. Prolonged combined therapy resulted in further EF improvement.
Conclusion. Combined fluvastatin XL and valsartan therapy in patients with untreated Stage I-II AH and DLP IIA or IIB improved EF more effectively than valsartan or fluvastatin XL monotherapy.
About the Authors
T. Sh. Mirilashvili
Russian People’s Friendship University; City Clinical Hospital No. 64
Russian Federation
Russian Federation
Moscow
S. V. Villewalde
Russian People’s Friendship University
Russian Federation
Russian Federation
Moscow
Yu. V. Kotovskaya
Russian People’s Friendship University
Russian Federation
Russian Federation
Moscow
Zh. D. Kobalava
Russian People’s Friendship University
Russian Federation
Russian Federation
Moscow
References
1. Thuillez C, Richard V. Targeting endothelial dysfunction in hypertensive subjects. J Hum Hypertens 2005; 19: 21-5.
2. Petricone F, Ceravolo R, Pujia A, et al. Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation 2001; 104: 191-6.
3. Spencer CGC, Gurney D, Blann AD, et al. Von Willebrand factor, soluble P selectin, and target organ damage in hypertension. A substudy of the Anglo Scandinavian Cardiac Outcomes Trial (ASCOT). Hypertension 2002; 40: 61-6.
4. Griendling KK, Ushio-Fukai M, Lassegue B, Alexander RW. Angiotensin II signaling in vascular smooth muscle: New concepts. Hypertension 1997; 29: 213-29.
5. Tsiara S, Elisaf M, Mikhailidis D. Early vascular benefits of statin therapy. Curr Med Res Opin 2003; 19: 540-56.
6. Диагностика и лечение артериальной гипертонии. Рекомендцаии Российского медицинского общества по артериальной гипертонии и Всероссийского научного общества кардиологов. Кардиоваск тер профил 2008; 7(6): Приложение 2.
7. Qadri F, Arens T, Schwartz EC, et al. Angiotensin-converting enzyme inhibitors and AT 1—receptor antagonist restore nitric oxide synthase (NOS) activity and neuronal NOS expression in the adrenal glands of spontaneously hypertensive rats. Jpn J Pharmacol 2001; 85: 365-9.
8. Schiffrin EL, Park JB, Touyz RM. Correction of Arterial Structure and Endothelial Dysfunction in Human Essential Hypertension by the Angiotensin Receptor Antagonist Losartan. Circulation 2000; 101: 1653.
9. Habib JB, Bossaller C, Wells S, et al. Preservation of endothelium—depent vascular relaxation in cholesterol—fed rabbit by treatment with the calcium blocker PN 200110. Circ Res 1986; 58: 305-9.
10. Ghiadoni L, Virdis A, Magagna A, et al. Effect of the Angiotensin II Type 1 Receptor Blocker Candesartan on Endothelial Function in Patients With Essential Hypertension. Hypertension 2000; 35: 501.
11. Li P, Fukuhara M, Diz DI, et al. Novel angiotensin II AT (1) receptor antagonist irbesartan prevents thromboxane A (2)—induced vasoconstriction in canine coronary arteries and human platelet aggregation. J Pharmacol Exp Ther 2000; 292: 238-46.
12. Siragy HM, de Gasparo M, Carey RM. Angiotensin type 2 receptor mediates valsartan—induced hypotension in conscious rats. Hypertension 2000; 35: 1074-7.
13. Ledingham JM, Laverty R. Basilar artery remodelling in the genetically hypertensive rat: effects of nitric oxide synthase inhibition and treatment with valsartan and enalapril. Clin Exp Pharmacol Physiol 2000; 27: 642-6.
14. Borghi C, Veronesi M, Prandin MG. Statins and blood pressure regulation. Curr Hypertens Rep 2001; 3: 281-8.
15. Strazzullo P, Kerry SM, Barbato A, et al. Do Statins Reduce Blood Pressure?: A Meta-Analysis of Randomized, Controlled Trials. Hypertension 2007; 49: 792-8.
16. Inoue T, Hayashi M, Takayanagi K, et al. Lipid-lowering therapy with fluvastatin inhibits oxidative modification of low density lipoprotein and improves vascular endothelial function in hypercholesterolemiс patients. Atherosclerosis 2002; 160: 369-76.
Review
For citations:
Mirilashvili T.Sh., Villewalde S.V., Kotovskaya Yu.V., Kobalava Zh.D. Effects of fluvastatin, valsartan, and their combination on endothelial function in patients with arterial hypertension and dyslipidemia. Cardiovascular Therapy and Prevention. 2009;8(4):28-32. (In Russ.)
Views:
619
Email this article 
