IPHAAB-study Influence of Physical Activity on Atherosclerosis Biomarkers

Influence of 8 Months of Increased Physical Activity Workload on Osteoprotegerin and Endocan Levels Clinical Trial

Official title:

Influence of Physical Activity on Promising Atherosclerosis Biomarkers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02097199
• Other study ID #: 1830/2013
• Status: Completed
• Phase: N/A
• First received: March 24, 2014
• Last updated: January 6, 2016
• Start date: August 2014
• Est. completion date: December 2015

Study information

• Verified date: January 2016
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Ethikkommission
• Study type: Observational

Clinical Trial Summary

This study investigates the influence of an increased physical activity and sports workload in formerly nonsporting healthy individuals on current promising biomarkers of atherosclerosis research.

Description:

According to Statistik Austria, cardiovascular disease (CVD) is the most common reason for death in Austria in total population. In 2011, 42,3 % of all deaths were due to CVD (ICD-10 I00-I99). In People aged 45-64 years, CVD is, beyond cancer, the second most common cause of death. According to the "Österreichische Gesundheitsbefragung 2006/7" more than two-thirds of men and three-quarters of women are physically inactive whereby physical inactivity was defined as at least 3x/week of sudatory exercise like cycling, jogging or aerobic.

A very famous study done by Morris et al. in 1953 showed that bus conductors in London (walking job) had half of the coronary heart disease (CHD) mortality compared to bus drivers (sitting job) and therefore initiated the hour of birth of CVD research in connection to physical (in)activity. Cardiorespiratory fitness might reduce does-dependently all cause cardiovascular mortality by 20-30 % (5-8) and the probability of developing CHD by 30-50 % (9-11).

Recently, CVD-research focuses on the investigation of blood-markers which indicate the presence of atherosclerosis and represent risk for development and genesis of CV events. E.g. inflammatory markers such as IL-6, TNF-alpha, ICAM-1, P-selectin, hsCRP and serum amyloid A are promising markers. Studies have shown that hsCRP levels at baseline predict future CV events. Markers of plaque stability are e.g. myeloperoxidase, metalloproteinase-9 and soluble CD-40 ligand. However, the influence of exercise on these factors has already been investigated.

The main dependent variables will be endocan and osteoprotegerin (OPG): OPG is a member of the TNF-related family and involved in bone metabolism. However, high levels of OPG have been reported in association with cardiovascular outcome (CAD, vascular calcification, advanced atherosclerosis, heart failure...). Serum concentrations were found to correlate with severity of peripheral artery disease, carotic stenosis and myocardial infarction. Furthermore, OPG is was associated with left ventricle and left atrial remodelling in patients with severe aortic stenosis, a disease which is often obverse in elderly patients. Age and gender were shown to predict OPG levels, at least in hemodialysis patients. Several studies have been performed investigating the influence of acute exercise or resistance training on circulating OPG amounts but less is known about the influence of long-term physical exercise.

Endocan (endothelial cell specific molecule 1; ESM-1) is a recombinant proteoglycan which may represent a new marker that correlates with CV risk and surrogate endothelial dysfunction playing a role in endothelium-dependent pathological disorders.

Other variables will be:

• Progerin: Progerin was originally investigated in course of research in Hutchinson-Gilford-Syndrome, a genetic effect which affects children leading to atherosclerosis. Progerin correlates with the vascular pathology of "normal" aging and is present also in the "normal" population.

• Myeloid-related protein 8 and 14 (MRP-8/14): MRP-8/14 is a stable heterodimer, formed by Ca++-binding proteins. It has been shown that MRP-8/14 regulates vascular inflammation, is involved in diabetic vascular complications and occurs in CAD. Furthermore, MRP-14 was associated with histopathologic findings and inflammation status in atherosclerotic plaques.

• Angiopoietin-like protein 2 (angptl2): Angptl2 depends to the family of angiopoietin-like proteins and is involved in angiogenesis. Angptl2 was shown to be 6 times higher in mice with CAD compared to controls. Furthermore, it increases with age but this increase was more pronounced in mice with high cholesterol levels. Angptl2 therefore contributes to the genesis and pathogenesis of atherosclerosis.

• Cathepsin S and K: Cathepsins are synthesized as inactive proenzymes and get activated by proteolytic processes. Atherosclerotic lesions contain much higher amounts of cathepsin S and K than normal arteries. Furthermore, they seem to play a role in the formation of aneurysms.

• Cystatin C: Cystatin C is a cysteine protease inhibitor participating in protein catabolism and has been suggested to predict CVD. High serum levels of cystatin c were shown to correlate with early stage atherosclerosis. Cystatin C is an independent predictor for the risk of cardiovascular events.

• Placental growth factor (PlGF): PlGF, a cysteine-knot protein which is quite homologous to VEGF, was implicated in the Pathophysiology of angiogenesis. PlGF-expression in atherosclerotic lesions was shown to be associated with inflammation and microvascular density suggesting PlGF to play a role in plaque destabilization and clinical manifestation of CAD (32). Anti-PlGF monoclonal antibody therapy in mice lead to a decrease in development of atherosclerosis.

All mentioned markers are of distinctive interest in atherosclerosis research, however, the influence of long-term exercise on them has not been studied yet.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: December 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 30 Years to 65 Years

Eligibility

Inclusion Criteria:

• Age 30-65 years

• less than 30 minutes of quick walking/day

• Physical ability to perform sports and bicycle stress tests

Exclusion Criteria:

• Age <30 or >65 years

• Pregnancy

• weight >130 kg

• untreated/uncontrolled hypertension

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Atherosclerosis
• Influence of 8 Months of Increased Physical Activity Workload on Osteoprotegerin and Endocan Levels

Intervention

Other:
• Increased sports workload
At least 150 minutes of moderate or 75 minutes of vigorous exercise per week. The "Recommendations for Adults From the American College of Sports Medicine and the American Heart Association" clearly define physical exercise intensity levels. The present study follows these recommendations. Consequently, moderate physical activity can be reached by e.g. quick walking, slow bicycling, slow swimming...; it is also possible to reach the expected workload by engaging in vigorous exercise (e.g. jogging/running, quick swimming, playing soccer/tennis...). The gain in performance will objectified by performing a bicycle stress test at the beginning and the end of the study.

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of Vienna	Austrian Federal Ministry of Defence and Sports

Country where clinical trial is conducted

Austria, 

References & Publications (3)

Sponder M, Dangl D, Kampf S, Fritzer-Szekeres M, Strametz-Juranek J. Exercise increases serum endostatin levels in female and male patients with diabetes and controls. Cardiovasc Diabetol. 2014 Jan 6;13:6. doi: 10.1186/1475-2840-13-6. — View Citation

Sponder M, Fritzer-Szekeres M, Marculescu R, Litschauer B, Strametz-Juranek J. Physical inactivity increases endostatin and osteopontin in patients with coronary artery disease. Heart Vessels. 2015 Dec 11. [Epub ahead of print] — View Citation

Sponder M, Sepiol K, Lankisch S, Priglinger M, Kampf S, Litschauer B, Fritzer-Szekeres M, Strametz-Juranek J. Endostatin and physical exercise in young female and male athletes and controls. Int J Sports Med. 2014 Dec;35(13):1138-42. doi: 10.1055/s-0034-1375692. Epub 2014 Jul 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline osteoprotegerin and endocan level to osteoprotegerin and endocan levels after 8 months of increased physical activity workload	Osteoprotegerin and endocan levels will be measured at baseline, every 2 months of training and at the end of the observation after 8 months	Baseline, Month 8	No
Secondary	Change from baseline Progerin, Myeloid-related peptide 8 and 14, Angiopoietin-like protein 2, Cathepsin S and K, Cystatin C and Placental growth factor level to levels after 8 months of increased physical activity workload	Progerin, Myeloid-related peptide 8 and 14, Angiopoietin-like protein 2, Cathepsin S and K, Cystatin C and Placental growth levels will be measured at baseline, every 2 months of training and at the end of the observation after 8 months	Baseline, Month 8	No