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Patients with primary hyperaldosteronism experience more cardiovascular events compared to patients with primary hypertension, independent of the blood pressure level.
In this research we hypothesize that patients with primary hyperaldosteronism are more susceptible to ischemia-reperfusion injury.
Patients with PHA have an increased risk of cardiovascular events, independent of blood pressure level. Also in patients suffering a myocardial infarction, circulating aldosterone levels are associated with increased mortality. In animal models of myocardial infarction, the administration of exogenous aldosterone increased infarct size, although other studies did not report this effect. In similar models, antagonists of the mineralocorticoid receptor (MR) reduced infarct size, which was completely abolished in ecto-5'-nucleotidase (CD73, the enzyme that catalyses extracellular formation of the endogenous nucleoside adenosine) and adenosine receptor knock-out mice. Therefore, we hypothesize that patients with PHA have an increased susceptibility for ischemia-reperfusion (IR)-injury due to down-regulation of the enzyme CD73. We will use the reduction in brachial flow-mediated dilation (FMD) by forearm IR as a well-validated endpoint for (endothelial) IR-injury.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Primary hyperaldosteronism | Active Comparator | patients with primary hyperaldosteronism will be subjected to the intervention forearm ischemia and reperfusion (20 minutes of forearm ischemia and 20 minutes of reperfusion). Primary endpoint is the reduction in brachial FMD by forearm ischemia-reperfusion, as a measure of endothelial ischemia-reperfusion injury |
|
| Primary hypertension | Placebo Comparator | Patients with primary hypertension (PHA excluded)will be subjected to 20 minutes of forearm ischemia and 20 minutes of reperfusion. Primary endpoint is the reduction in brachial FMD by forearm ischemia-reperfusion, as a measure of endothelial ischemia-reperfusion injury |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| forearm ischemia and reperfusion | Procedure | both arms will be subjected to 20 minutes of forearm ischemia and 20 minutes of reperfusion. |
|
| Measure | Description | Time Frame |
|---|---|---|
| brachial FMD | primary outcome measure is the reduction in brachial artery FMD after 20 minutes of forearm ischemia and 20 minutes of reperfusion in patients with primary hyperaldosteronism (compared to patients with primary hypertension) | 1 day morning |
| Measure | Description | Time Frame |
|---|---|---|
| CD73 and adenosine | Blood will be drawn to determine circulating adenosine concentration and the CD73 activity on mononuclear cells | one day morning (just before FMD experiment) |
| Measure | Description | Time Frame |
|---|---|---|
| aldosterone and renin | Just before the FMD experiment, blood will be drawn for aldosterone and renin levels. These levels will not be determined, unless the brachial artery FMD after ischemia and reperfusion is significantly reduced in patients with primary hyperaldosteronism. We will store the plasma and serum at -20 C. If applicable, the aldosterone and aldosterone-to-renin ratio will be determined to correlate the primary outcome measure to the aldosterone and ARR levels. |
Inclusion Criteria patients with primary hyperaldosteronism:
Inclusion Criteria patients with primary hypertension:
Exclusion Criteria for both arms (patients with primary hyperaldosteronism and patients with primary hypertension:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Radboud University Medical Centre | Nijmegen | Gelderland | 6525EZ | Netherlands |
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| ID | Term |
|---|---|
| D006929 | Hyperaldosteronism |
| D000075222 | Essential Hypertension |
| ID | Term |
|---|---|
| D000308 | Adrenocortical Hyperfunction |
| D000307 | Adrenal Gland Diseases |
| D004700 | Endocrine System Diseases |
| D006973 | Hypertension |
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| ID | Term |
|---|---|
| D015424 | Reperfusion |
| ID | Term |
|---|---|
| D013504 | Cardiovascular Surgical Procedures |
| D013514 | Surgical Procedures, Operative |
| D010477 | Perfusion |
| D008919 | Investigative Techniques |
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| 1 day |
| leukocyte telomere length (LTL) | We will measure LTL in 12 patients with PHA and 12 patients with EHT to assess wether aldosterone excess increases telomere shortening in patients with PHA | 1 day |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |