To investigate the genetic, genomic and proteomic basis of hypertension and susceptibility to hypertension-related target-organ damage (renal insufficiency and heart failure).
ID
Source
Brief title
Condition
- Heart failures
- Nephropathies
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To analyse genetic and genomic factors involved in the pathogenesis of
hypertension.
To analyse genetic, genomic and proteomic factors involved in changes in
microalbuminuria.
To analyse genetic, genomic and proteomic factors involved in changes in
cardiac and large artery structure and function.
Secondary outcome
To analyse the proteomic factors involves in the pathogenesis of hypertension.
To explore the role of oxidative stress and microinflammation in the
pathogenesis of hypertension.
To analyse genetic, genomic and proteomic factors associated with renal
phenotypes in hypertensive subjects: elevated urinary albumin excretion
(microalbuminuria, proteinuria) salt-sensitivity, reduced GFR, and end-stage
renal disease.
To analyse genetic, genomic and proteomic factors associated with presence or
development of heart dysfunction and failure in hypertensive patients.
Background summary
Hypertension and its cardiovascular consequences are a major cause of mortality
and morbidity. The knowledge and experience in the mechanisms of blood pressure
control, the development of hypertension and hypertension related organ damage
is still very fragmented. The InGenious HyperCare network aims to integrate
this knowledge and to build up comprehensive databases of common phenotypes,
genotypes and proteomic data from hypertensive subjects. The current Joint
Research Project (JRP A2-B2-B3) focuses on the so-called *mechanomics* of
hypertension: genetic, genomic and proteomic markers of disturbances in the
major mechanisms (inflammation and oxidative stress) involved in the
development of hypertension and hypertension related organ damage (renal
insufficiency and heart failure). Hypertension-related organ disease results
from arterial and arteriolar damage. Important mediators of this damage are
activation of the renin-angiotensin system, fibrosis, hypertrophy and
inflammation. Inflammation is thought to be an important link between
hypertension, endothelial dysfunction, oxidative stress and ultimately organ
damage. Both hypertension and oxidative stress are known to cause endothelial
dysfunction and an inflammatory cascade involving expression of endothelial
adhesion molecules. These molecules facilitate leukocyte infiltration of the
extracellular matrix, leading to altered cell-signalling, production of growth
factors, production of matrix proteins and proliferation of vascular smooth
muscle cells, all contributing to vascular damage. Genetic factors seem to play
a prominent role in these mechanisms. This is supported by the fact that both
hypertension in itself and hypertension related renal disease have a strong
familial occurrence. Nevertheless, studies investigating the link between
genetics and different cardiovascular phenotypes have not given univocal
results. Therefore, the present study aims to investigate genetic, genomic and
proteomic factors involved in inflammation and oxidative stress in hypertension
and its related organ damage.
Study objective
To investigate the genetic, genomic and proteomic basis of hypertension and
susceptibility to hypertension-related target-organ damage (renal insufficiency
and heart failure).
Study design
The present study is a large, multicenter, observational family-study with
follow-up moments after 2 and 4 years. Subjects and family-members will undergo
extensive cardiovascular phenotyping involving a complete medical history,
physical examination, measurement of the carotid Intima Media Thickness (cIMT),
Pulse-wave velocity, ECG, cardiac ultrasonography, ambulatory blood-pressure
measurement (ABPM) and laboratory tests of blood and urine. Data is collected
from over 30 research-centres in Europe and is integrated in a large central
database.
Study burden and risks
Subjects will visit the research-laboratory for two hours on two consecutive
days. During these visits the medical history, physical examination and the
other investigations will be performed. Blood samples will be obtained by
venipuncture. There is a risk of hematoma-development after venipuncture. In
addition are subjects required to collect a morning-sample of urine on two
days. The investigations will be repeated after two and four years.
Postbus 5800
6202 AZ Maastricht
Nederland
Postbus 5800
6202 AZ Maastricht
Nederland
Listed location countries
Age
Inclusion criteria
- Men or women between 18 and 60 years of age at time of enrolment
- Essential hypertension diagnosed before the age of 50 years.
- At least 3 first-degree relatives of whom at least 1 should have hypertension and at least one from a different generation, willing to participate in the study.
- Written informed consent
Exclusion criteria
- Any known form of secondary hypertension,
- Any known previous clinical complications of hypertension (angina, myocardial infarction, stroke, TIA, peripheral artery disease) at any time
- known renal disease, including GFR < 60 mL/min/1.73 m2 as estimated by the abbreviated MDRD formula, or kidney stones
- Kidney or other organ transplantation
- Type 1 diabetes mellitus
- Heart failure stage D (AHA/ACC criteria)
- Any malignant concomitant diseases or history of malignant diseases within the last five years, with exception of treated squamous skin cancer or basalioma
- Clinical or laboratory signs of acute infection.
- Systemic inflammatory diseases,
- Steroids or any other immunosuppressive drug
- Severe known liver disease (ALT or gamma-GT above three-fold of upper normal limit)
- Current alcohol consume of more than 21 drinks/week or drug abuse
- Pregnancy
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL26082.068.08 |