IPHAAB-study Influence of Physical Activity on Atherosclerosis Biomarkers
- Conditions
- Influence of 8 Months of Increased Physical Activity Workload on Osteoprotegerin and Endocan Levels
- Interventions
- Other: Increased sports workload
- Registration Number
- NCT02097199
- Lead Sponsor
- Medical University of Vienna
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 98
- Age 30-65 years
- less than 30 minutes of quick walking/day
- Physical ability to perform sports and bicycle stress tests
- Age <30 or >65 years
- Pregnancy
- weight >130 kg
- untreated/uncontrolled hypertension
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Sports group Increased sports workload The cohort 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) who want to engage more in physical activity (at least 150 minutes of at least moderate intensity per week). The gain in workload will be objectified and quantified by performing a bicycle stress test at the beginning of the study and after 8 months of physical engagement.
- Primary Outcome Measures
Name Time Method Change from baseline osteoprotegerin and endocan level to osteoprotegerin and endocan levels after 8 months of increased physical activity workload Baseline, Month 8 Osteoprotegerin and endocan levels will be measured at baseline, every 2 months of training and at the end of the observation after 8 months
- Secondary Outcome Measures
Name Time Method 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 Baseline, Month 8 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
Trial Locations
- Locations (1)
Medical University of Vienna
🇦🇹Vienna, Austria