Malignant Hypertension
Conditions
Keywords
malignant hypertension, severe hypertension, hypertensive emergency, pathophysiology, angiogenic system, inflammasome
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 Recent unpublished animal data highlight 1/ the possibility of severe deregulation of the VEGF (vascular endothelial growth factor) system in malignant hypertension 2/ the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.
Interventions
BIOLOGICALanalyse of angiogenic, vasoactive and VEGF systems
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.
Sponsors
Centre Hospitalier de PAU
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| sFLT1 concentration at inclusion | at the end of study recrutment, an average of 11 month | The primary endpoint will be the difference in sFLT1 concentrations between patients and controls at enrolment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| VEGF concentration at inclusion | at the end of study recrutment, an average of 11 month | Difference in VEGF concentrations between patients and controls at enrolment |
| renin concentration at inclusion | at the end of study recrutment, an average of 11 month | Difference in renin concentrations between patients and controls at enrolmentD30, and compare this evolution. |
| angiotensin concentration at inclusion | at the end of study recrutment, an average of 11 month | Difference in angiotensin concentrations between patients and controls at enrolmentD30, and compare this evolution. |
| evolution of IL1ß concentration | through study completion, an average of 12 month | Evaluation of the evolution of IL1ß concentration in the two groups between D0 and D30, and compare this evolution. |
| IL1ß concentration at inclusion | at the end of study recrutment, an average of 11 month | Difference in IL1ß concentrations between patients and controls at enrolment |
| evolution of renin concentration | through study completion, an average of 12 month | Evaluation of the evolution of renin concentration in the two groups between D0 and D30, and compare this evolution. |
| evolution of angiotensin concentration | through study completion, an average of 12 month | Evaluation of the evolution of angiotensin concentration in the two groups between D0 and D30, and compare this evolution. |
| mutations in the genes of interest | through study completion, an average of 11 month | comparison in the 2 groups of the frequency of mutations in the genes of interest underlying the vasoactive, angiogenic and VEGF systems |
| evolution of VEGF concentration | through study completion, an average of 12 month | Evaluation of the evolution of VEGF concentration in the two groups between D0 and D30, and compare this evolution. |
Countries
France
Outcome results
None listed