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
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.
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.
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Time Perspective: Prospective