Clinical trial NCT04991077: Interrupters of VAscular daMAge in Malignant Hypertension
Official title: Interrupters of VAscular daMAge in Malignant Hypertension: Role of Inflammasome, Angiogenic and Vasoactive System
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Malignant Hypertension
Keywords: malignant hypertension
severe hypertension
hypertensive emergency
pathophysiology
angiogenic system
inflammasome
Lead sponsor: Centre Hospitalier de PAU
Sponsor class: OTHER
First posted: 2021-08-05
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patient group: patient with malignant hypertension control group: paitent with severe hypertension

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 Recent unpublished animal data highlight 1/ the possibility of severe deregulation of the VEGF (vascular endothelial growth factor) system in malignant hypertension 2/ the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.

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

Primary outcomes:
measure: sFLT1 concentration at inclusion
timeFrame: at the end of study recrutment, an average of 11 month
Secondary outcomes:
measure: IL1ß concentration at inclusion
timeFrame: at the end of study recrutment, an average of 11 month
measure: VEGF concentration at inclusion
timeFrame: at the end of study recrutment, an average of 11 month
measure: renin concentration at inclusion
timeFrame: at the end of study recrutment, an average of 11 month
measure: angiotensin concentration at inclusion
timeFrame: at the end of study recrutment, an average of 11 month
measure: evolution of IL1ß concentration
timeFrame: through study completion, an average of 12 month
measure: evolution of VEGF concentration
timeFrame: through study completion, an average of 12 month
measure: evolution of renin concentration
timeFrame: through study completion, an average of 12 month
measure: evolution of angiotensin concentration
timeFrame: through study completion, an average of 12 month
measure: mutations in the genes of interest
timeFrame: through study completion, an average of 11 month
Other outcomes:
Locations:
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Paris
country: France
facility: Hôpital Bichat
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: Hôpital Tenon
city: Toulouse
country: France
facility: Chu Rangueil
city: Tours
country: France
facility: CHU de Tours
Study officials:
References: