IPHAAB-study Influence of Physical Activity on Atherosclerosis Biomarkers
Condition: Influence of 8 Months of Increased Physical Activity Workload on Osteoprotegerin and Endocan Levels
MeSH terms: Atherosclerosis
Study type: Observational

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.
    

Detailed 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.
    

Intervention name(s): Increased sports workload
Intervention type(s): Other
Intervention description(s): 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.
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        The study population will consist of about 55 female and 55 male individuals aged 30-65
        years with mostly sedentary work (>6 hours/day) doing no or less physical activity (<30
        minutes quick walking/day).
      
Biospecimen description: 
      whole blood
    
Keywords: activity, osteoprotegerin, endocan, atherosclerosis, biomarker