Prevalent OPG and RANKL Excession in Patients With CAD Clinical Trial
Official title:
Graz Osteoprotegerin as a Risk Factor (GORF) Study: THE ROLE of OSTEOPROTEGERIN (OPG) and the RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-Kb LIGAND (RANKL) IN PATIENTS REQUIRING SURGERY FOR CORONARY HEART DISEASE
Osteoprotegerin (OPG) is membrane bound in the immune system but can also be produced and
secreted almost everywhere in the organism, so that it is mainly available in soluble form.
So far, the OPG/RANKL/RANK system has been most intensively studied in bone. The binding of
RANKL on its receptor RANK, which is expressed by osteoclasts, activates a number of
osteoclastic cell functions. OPG also has a key function in the vascular system. Patients
with coronary heart disease (CAD) have elevated OPG serum levels, probably as a sign of
ischemic or inflammatory endothelial damage. Elevated OPG levels were also found in patients
with advanced heart failure, whereby OPG correlated with pro BNP (brain natriuretic peptide)
and was a predictor for cardiovascular morbidity and mortality.
Our prospective cohort study will include 150 men (75 patients requiring surgery for CAD and
a control group without coronary heart disease). The primary endpoints are the differences
between the two groups in serum levels of OPG and RANKL, markers of bone metabolism
(osteocalcin [OC], crosslaps [CTX], tartrate resistant acid phosphatase (TRAP5b), 25(OH)
vitamin D [Vit D], 1.25(OH) vitamin D, parathormone [iPTH], endocrine parameters related to
vascular damage (e.g. aldosterone, renin and cortisol) and bone mineral density. Metabolomic
based biomarkers will be evaluated to explore the mechanisms behind OPG-RANKL linked CVD
damage. In the patients further studies of the mRNA expression of OPG, RANKL, TRAP5b,
arginine:glycine amidinotransferase (AGAT) and osteocalcin in bone (sternum sliver) and
vascular wall (aorta, internal thoracic artery and the great saphenous vein) will be
performed.
A further study endpoint is the analysis of a causal coincidence between osteoporosis and
CAD and the discrimination of possible key factors in the two entities. These will be
determined by the correlation between the above-mentioned markers in serum and the
expression in different vessels and in bone tissue.
In addition to analysis of the degree of vascular sclerosis, the mineral content of the bone
will also be analyzed in a subpopulation with quantitative backscattered electron imaging
(qBEI) related to the degree of vascular sclerosis and bone mineral density. The ultimate
goal of the analysis is the discrimination of the most sensitive predictive marker(s) for
diagnosis and outcome of patients with CAD for the purpose of early diagnosis and primary
prevention of the disease.
CAD and osteoporosis are increasingly prevalent diseases that overlap. In both entities, OPG
plays a role not only in pathogenesis but also as an outcome predictor. We aim to study the
relevance of OPG concentration in serum but also in the vessel wall and the bone.
| Status | Recruiting |
| Enrollment | 150 |
| Est. completion date | September 2012 |
| Est. primary completion date | July 2012 |
| Accepts healthy volunteers | No |
| Gender | Male |
| Age group | 40 Years to 90 Years |
| Eligibility |
Inclusion Criteria: - Male patients above 40 years of age presenting with symptomatic CAD and scheduled for a coronary artery bypass graft (CABG) are eligible for the study. The control group includes male patients scheduled for elective surgery other than cardiac procedures. Exclusion Criteria: - Exclusion criteria are a second indication for heart surgery, chronic renal disease with a glomerular filtration rate < 30ml/min, advanced liver disease (AST, ALT, GGT > 3fold upper limit of normal), history of malignancy within the last 5 years and ongoing osteoprotective treatment. |
Observational Model: Cohort, Time Perspective: Prospective
| Country | Name | City | State |
|---|---|---|---|
| Austria | Medical University of Graz | Graz |
| Lead Sponsor | Collaborator |
|---|---|
| Medical University of Graz | Medical University of Vienna |
Austria,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | OSTEOPROTEGERIN (OPG) | The primary endpoints are the differences between the two groups in serum levels of OPG and RANKL, markers of bone metabolism (osteocalcin [OC], crosslaps [CTX], tartrate resistant acid phosphatase (TRAP5b), 25(OH) vitamin D [Vit D], 1.25(OH) vitamin D, parathormone [iPTH], endocrine parameters related to vascular damage (e.g. aldosterone, renin and cortisol) and bone mineral density. | Baseline at time 0 (at the beginning of the study). The participants will be followed for the duration of hospital stay, an expected average of 10 days. | Yes |
| Secondary | RANKL | The primary endpoints are the differences between the two groups in serum levels of OPG and RANKL, markers of bone metabolism (osteocalcin [OC], crosslaps [CTX], tartrate resistant acid phosphatase (TRAP5b), 25(OH) vitamin D [Vit D], 1.25(OH) vitamin D, parathormone [iPTH], endocrine parameters related to vascular damage (e.g. aldosterone, renin and cortisol) and bone mineral density. | At baseline. The participants will be followed for the duration of hospital stay, an expected average of 10 days. | Yes |