Preventive Arterial Wall Phenotype and Low-dose Fluvastatin/Valsartan Combination

Atherosclerosis Clinical Trial

— AGE-ZT  

Official title:

Preventive Arterial Wall Phenotype in Subjects at Moderate Cardiovascular Risk Induced by Very Low-dose Fluvastatin/Valsartan Combination: a Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03393377
• Other study ID #: AGE-ZT
• Status: Completed
• Phase: N/A
• First received: December 29, 2017
• Last updated: January 5, 2018
• Start date: September 2014
• Est. completion date: June 2017

Study information

• Verified date: January 2018
• Source: University Medical Centre Ljubljana
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study was designed to test whether short-term treatment with a very low-dose combination of fluvastatin and valsartan could induce improvement of endothelial function, arterial stiffness, vascular inflammation, oxidative stress and expression of protective genes in subjects with moderate cardiovascular risk.

Description:

The largest population that suffers from cardiovascular events are subjects at moderate cardiovascular risk. However, no effective and safe preventive treatment is available for this population. This study aimed to investigate whether their arterial wall phenotype could be turned to a preventive direction by low-dose fluvastatin/valsartan combination (low-flu/val).

Twenty males at moderate cardiovascular risk (as classified by SCORE) were blindly randomised into the intervention group (n=10, low-flu/val: 10 mg/20mg) or control group (n=10, placebo). At inclusion and after 30 days of treatment, brachial flow-mediated dilatation (FMD), beta stiffness coefficient, carotid pulse wave velocity (c-PWV), carotid-femoral PWV, reactive hyperaemia index, high-sensitivity C-reactive protein (hs-CRP), interleukin 6, vascular cell adhesion molecule 1, total antioxidant status and expression of several protective genes (SIRT1, mTOR, NF-κB1, NFE2L2, PRKAA1) were followed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 2017
• Est. primary completion date: June 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 40 Years to 55 Years

Eligibility

Inclusion Criteria:

• moderate cardiovascular risk according to Systematic Coronary Risk Estimation (SCORE) risk charts of the European Society of Cardiology

• males

• aged between 40 and 55 years

Exclusion Criteria:

• diabetes mellitus

• manifest peripheral artery disease or carotid artery disease

• acute infection

• chronic diseases

• present therapy with fluvastatin and/or valsartan

Related Conditions & MeSH terms

• Atherosclerosis

Intervention

Drug:
• fluvastatin 10 mg and valsartan 20 mg

• placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Centre Ljubljana

References & Publications (10)

Boncelj Svetek M, Eržen B, Kanc K, Šabovic M. Impaired endothelial function and arterial stiffness in patients with type 2 diabetes - The effect of a very low-dose combination of fluvastatin and valsartan. J Diabetes Complications. 2017 Mar;31(3):544-550. doi: 10.1016/j.jdiacomp.2016.12.002. Epub 2016 Dec 16. — View Citation

Janic M, Lunder M, Prezelj M, Šabovic M. A combination of low-dose fluvastatin and valsartan decreases inflammation and oxidative stress in apparently healthy middle-aged males. J Cardiopulm Rehabil Prev. 2014 May-Jun;34(3):208-12. doi: 10.1097/HCR.0000000000000027. — View Citation

Lunder M, Janic M, Jug B, Sabovic M. The effects of low-dose fluvastatin and valsartan combination on arterial function: a randomized clinical trial. Eur J Intern Med. 2012 Apr;23(3):261-6. doi: 10.1016/j.ejim.2011.11.011. Epub 2011 Dec 12. — View Citation

Matsuzawa Y, Kwon TG, Lennon RJ, Lerman LO, Lerman A. Prognostic Value of Flow-Mediated Vasodilation in Brachial Artery and Fingertip Artery for Cardiovascular Events: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2015 Nov 13;4(11). pii: e002270. doi: 10.1161/JAHA.115.002270. Review. — View Citation

Paneni F, Diaz Cañestro C, Libby P, Lüscher TF, Camici GG. The Aging Cardiovascular System: Understanding It at the Cellular and Clinical Levels. J Am Coll Cardiol. 2017 Apr 18;69(15):1952-1967. doi: 10.1016/j.jacc.2017.01.064. Review. — View Citation

Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, Cooney MT, Corrà U, Cosyns B, Deaton C, Graham I, Hall MS, Hobbs FD, Løchen ML, Löllgen H, Marques-Vidal P, Perk J, Prescott E, Redon J, Richter DJ, Sattar N, Smulders Y, Tiberi M, van der Worp HB, van Dis I, Verschuren WM; Authors/Task Force Members. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016 Aug 1;37(29):2315-81. doi: 10.1093/eurheartj/ehw106. Epub 2016 May 23. — View Citation

Robinson JG, Gidding SS. Curing atherosclerosis should be the next major cardiovascular prevention goal. J Am Coll Cardiol. 2014 Jul 1;63(25 Pt A):2779-85. doi: 10.1016/j.jacc.2014.04.009. Epub 2014 May 7. — View Citation

Sosnowska B, Mazidi M, Penson P, Gluba-Brzózka A, Rysz J, Banach M. The sirtuin family members SIRT1, SIRT3 and SIRT6: Their role in vascular biology and atherogenesis. Atherosclerosis. 2017 Oct;265:275-282. doi: 10.1016/j.atherosclerosis.2017.08.027. Epub 2017 Aug 26. Review. — View Citation

Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol. 2010 Mar 30;55(13):1318-27. doi: 10.1016/j.jacc.2009.10.061. Review. — View Citation

Yusuf S, Bosch J, Dagenais G, Zhu J, Xavier D, Liu L, Pais P, López-Jaramillo P, Leiter LA, Dans A, Avezum A, Piegas LS, Parkhomenko A, Keltai K, Keltai M, Sliwa K, Peters RJ, Held C, Chazova I, Yusoff K, Lewis BS, Jansky P, Khunti K, Toff WD, Reid CM, Varigos J, Sanchez-Vallejo G, McKelvie R, Pogue J, Jung H, Gao P, Diaz R, Lonn E; HOPE-3 Investigators. Cholesterol Lowering in Intermediate-Risk Persons without Cardiovascular Disease. N Engl J Med. 2016 May 26;374(21):2021-31. doi: 10.1056/NEJMoa1600176. Epub 2016 Apr 2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	brachial flow-mediated dilatation (FMD)	FMD measured by ultrasound on right brachial artery (as result of reactive hyperaemia)	30 days
Primary	reactive hyperaemia index (RHI)	RHI measured by Endopat device	30 days
Primary	beta stiffness coefficient	assessed by ultrasound employing e-Tracking on right common carotid artery	30 days
Primary	carotid pulse wave velocity (c-PWV)	assessed by ultrasound employing e-Tracking on right common carotid artery	30 days
Primary	carotid-femoral PWV (cf-PWV)	cf-PWV measured by Sphygmocor device	30 days
Primary	high-sensitivity C-reactive protein (hs-CRP)	inflammatory marker	30 days
Primary	interleukin 6 (IL-6)	inflammatory marker	30 days
Primary	vascular cell adhesion molecule 1 (VCAM1)	inflammatory marker	30 days
Primary	total antioxidant status (TAS)	marker of oxidative stress	30 days
Primary	gene SIRT1	Hs01009006_m1	30 days
Primary	gene mTOR	Hs00234522_m1	30 days
Primary	gene NF-kB1	Hs00765730_m1	30 days
Primary	gene Nrf2/NFE2L2	Hs00975961_g1	30 days
Primary	gene AMPK/PRKAA1	Hs01562315_m1	30 days
Secondary	brachial flow-mediated dilatation (FMD)	FMD measured by ultrasound on right brachial artery (as result of reactive hyperaemia)	10 weeks after treatment completion
Secondary	reactive hyperaemia index (RHI)	RHI measured by Endopat device	10 weeks after treatment completion
Secondary	beta stiffness coefficient	assessed by ultrasound employing e-Tracking on right common carotid artery	10 weeks after treatment completion
Secondary	carotid pulse wave velocity (c-PWV)	assessed by ultrasound employing e-Tracking on right common carotid artery	10 weeks after treatment completion
Secondary	carotid-femoral PWV (cf-PWV)	cf-PWV measured by Sphygmocor device	10 weeks after treatment completion