Interrupters of VAscular daMAge in Malignant Hypertension

Study Overview
=================
Brief Summary
-----------------
The pathophysiology of malignant hypertension is poorly understood. The objective of this translational research project is to evaluate the relationship between activation of vasoactive systems (renin-angiotensin and endothelin systems), angiogenic signal deficiency (VEGF and sFlt-1) and the occurrence of malignant hypertension episodes in humans.

Detailed Description
-----------------
The pathophysiology of malignant hypertension is poorly understood. The current dogma is based on an overwhelming renin-angiotensin-aldosterone system activation, leading to arterial hypertension that overcomes target organ auto-regulatory mechanisms and leads to subacute microvascular lesions. However, some patients present with normal or lowered renin in the acute phase of malignant hypertension, suggesting other pathophysiological pathways. Malignant hypertension was reported following anti-VEGF treatment, suggesting that this pathway may be involved. Recent unpublished animal data highlight 1/ the possibility of severe deregulation of the VEGF (vascular endothelial growth factor) system in malignant hypertension 2/ the possibility of compensation of the vasculotoxic effects of VEGF deficiency by inflammasome components. These systems have never been studied together in human hypertension. Investigators will analyze the angiogenic, vasoactive and VEGF systems through blood and urine sampling. These samples will be collected at the time of malignant hypertension diagnosis and repeated one month later in 30 patients. The same tests will be performed in 15 patients with severe non-malignant hypertension, constituting the control group.

Official Title
-----------------
Interrupters of VAscular daMAge in Malignant Hypertension: Role of Inflammasome, Angiogenic and Vasoactive System

Conditions
-----------------
Malignant Hypertension

Intervention / Treatment
-----------------
* Biological: analyse of angiogenic, vasoactive and VEGF systems


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients group : Patients included in the HAMA cohort Who is willing to take part in the IVAMA project Control group : Grade 2 or 3 hypertension with office blood pressure measurement (above 160 and/or 100 mmHg for systolic and diastolic) Persistence of blood pressure above 160 / 100 mmHg on the average of 3 attended blood pressure measurements Exclusion criteria: Patients group : Age < 18 years old Patients with chronic renal failure of stage 3 or higher. Patients with any type of diabetes Patient in per partum Patients who cannot freely give their consent, or patients who refuse to participate Chronic dialysis patient Control group: Evidence of subacute involvement of one of the following target organs: brain, kidney, eye, heart, thrombotic microangiopathy. Target organ impairment is defined in the inclusion criteria for the Patients group. Presence of known chronic kidney insufficiency of grade 3 or higher Chronic dialysis patient Diabetes of any type Patients who cannot freely give their consent, or patients who refuse to participate

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| patients group<br>patients with malignant hypertension | Biological: analyse of angiogenic, vasoactive and VEGF systems<br>* the angiogenic, vasoactive and VEGF systems will be analysed through blood and urine sampling. These samples will be collected at the time of malignant hypertension diagnosis and repeated one month later, in 30 patients (patients group). The same tests will be performed once in 15 patients with severe non-malignant hypertension, constituting the control group.<br>|
| Control group<br>patients with severe hypertension (Grade 2 or 3 hypertension) | Biological: analyse of angiogenic, vasoactive and VEGF systems<br>* the angiogenic, vasoactive and VEGF systems will be analysed through blood and urine sampling. These samples will be collected at the time of malignant hypertension diagnosis and repeated one month later, in 30 patients (patients group). The same tests will be performed once in 15 patients with severe non-malignant hypertension, constituting the control group.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sFLT1 concentration at inclusion | The primary endpoint will be the difference in sFLT1 concentrations between patients and controls at enrolment | at the end of study recrutment, an average of 11 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IL1ß concentration at inclusion | Difference in IL1ß concentrations between patients and controls at enrolment | at the end of study recrutment, an average of 11 month | 
| VEGF concentration at inclusion | Difference in VEGF concentrations between patients and controls at enrolment | at the end of study recrutment, an average of 11 month | 
| renin concentration at inclusion | Difference in renin concentrations between patients and controls at enrolmentD30, and compare this evolution. | at the end of study recrutment, an average of 11 month | 
| angiotensin concentration at inclusion | Difference in angiotensin concentrations between patients and controls at enrolmentD30, and compare this evolution. | at the end of study recrutment, an average of 11 month | 
| evolution of IL1ß concentration | Evaluation of the evolution of IL1ß concentration in the two groups between D0 and D30, and compare this evolution. | through study completion, an average of 12 month | 
| evolution of VEGF concentration | Evaluation of the evolution of VEGF concentration in the two groups between D0 and D30, and compare this evolution. | through study completion, an average of 12 month | 
| evolution of renin concentration | Evaluation of the evolution of renin concentration in the two groups between D0 and D30, and compare this evolution. | through study completion, an average of 12 month | 
| evolution of angiotensin concentration | Evaluation of the evolution of angiotensin concentration in the two groups between D0 and D30, and compare this evolution. | through study completion, an average of 12 month | 
| mutations in the genes of interest | comparison in the 2 groups of the frequency of mutations in the genes of interest underlying the vasoactive, angiogenic and VEGF systems | through study completion, an average of 11 month | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
severe hypertension, malignant hypertension, hypertensive emergency, pathophysiology, angiogenic system, inflammasome