Interrupters of VAscular daMAge in Malignant Hypertension: Role of Inflammasome, Angiogenic and Vasoactive System
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 7
- 主要终点
- sFLT1 concentration at inclusion
研究概览
简要总结
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.
详细描述
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 Recent unpublished animal data highlight 1/ the possibility of severe deregulation of the VEGF (vascular endothelial growth factor) system in malignant hypertension 2/ the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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- 未提供
研究组 & 干预措施
patients group
patients with malignant hypertension
干预措施: analyse of angiogenic, vasoactive and VEGF systems (Biological)
Control group
patients with severe hypertension (Grade 2 or 3 hypertension)
干预措施: analyse of angiogenic, vasoactive and VEGF systems (Biological)
结局指标
主要结局
sFLT1 concentration at inclusion
时间窗: 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
次要结局
- VEGF concentration at inclusion(at the end of study recrutment, an average of 11 month)
- renin concentration at inclusion(at the end of study recrutment, an average of 11 month)
- evolution of renin concentration(through study completion, an average of 12 month)
- IL1ß concentration at inclusion(at the end of study recrutment, an average of 11 month)
- evolution of VEGF concentration(through study completion, an average of 12 month)
- evolution of angiotensin concentration(through study completion, an average of 12 month)
- angiotensin concentration at inclusion(at the end of study recrutment, an average of 11 month)
- evolution of IL1ß concentration(through study completion, an average of 12 month)
- mutations in the genes of interest(through study completion, an average of 11 month)