Prospective Study on Primary Aldosteronism in Resistant Hypertension

Study Overview
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Brief Summary
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Prevalence of primary aldosteronism (PA) in resistant hypertension is not clear. In addition, emerging evidence supports the role of elevated serum aldosterone in promoting cardiovascular disease, independently from high blood pressure (BP) levels, but current data on this issue are heterogeneous.

Detailed Description
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PA is the most frequent form of secondary hypertension, with a prevalence that increases with the severity of hypertension. The wide variation of the reported PA prevalence is due to different study design and population. Very few data derive from well designed prospective study. Additional problems in the interpretation of study results are the different diagnostic cut-off used in various centers and the low diffusion of the adrenal vein sampling, that has a central role in the PA diagnosis. Resistant hypertension (RH) is a condition of insufficient BP control, despite appropriate lifestyle measures and treatment with at least 3 drugs at full dose, including a diuretic, in patients whose adherence to therapy has been confirmed. The primary aim of our study is define prospectively the prevalence of PA in RH. Moreover, emerging evidence supports the crucial role of elevated serum aldosterone in promoting cardiovascular disease, independently from high BP levels. Aldosterone improves oxidative stress, inflammation, impairs insulin metabolic signaling, reduced endothelial-mediated vasorelaxation and is associated to cardiovascular and renal abnormalities. However, current data on the contribution of PA on cardiometabolic complications have heterogeneous results. The secondary outcome of our study is to investigate prospectively the association of PA with cardiometabolic complications in a cohort of patients with RH.

Official Title
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Prospective Cross-sectional Study on Prevalence of Primary Aldosteronism in Resistant Hypertension and Association With Cardiometabolic Complications

Conditions
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Resistant Hypertension, Primary Aldosteronism, Refractory Hypertension, Hypertensive End-Organ Damage, Atrial Fibrillation, Aortic Ectasia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age over 18 and under 80 years old; diagnosis of resistant hypertension defined as: uncontrolled blood pressure at ambulatory blood pressure measurement (ABPM), despite the use of at least 3 antihypertensive drugs at full dose, including a diuretic. Exclusion Criteria: age under 18 or over 80 years old; pseudo-resistant hypertension (poor medication adherence, high salt intake); previous cardiovascular disease; insulin treated diabetes mellitus; other than primary aldosteronism cause of secondary hypertension (obstructive sleep apnea, renal artery stenosis, pheochromocytoma/paraganglioma, primary hyperparathyroidism, autonomous cortisol secretion or over hypercortisolism); liver cirrhosis; chronic heart failure; known malignant neoplasm; chronic disease with major organ involvement; excessive alcohol ingestion; current steroids assumption; use of sympathomimetic drugs; use of contraceptives.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of diagnosis (prevalence) of primary aldosteronism in prospective cohort of patients with resistant hypertension. | Basal Aldosterone (pg/mL) at baseline. | Baseline. | 
| Number of diagnosis (prevalence) of primary aldosteronism in prospective cohort of patients with resistant hypertension. | Basal Plasma Renin Activity (PRA, ng/mL/h) at baseline. | Baseline. | 
| Number of diagnosis (prevalence) of primary aldosteronism in prospective cohort of patients with resistant hypertension. | Aldosterone (pg/mL) post saline infusion test, performed at baseline. | Baseline. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular hypertrophy in primary aldosteronism and essential resistant hypertension | Left ventricular mass evaluation with Echocardiogram at baseline. | Baseline. | 
| Microalbuminuria in primary aldosteronism and essential resistant hypertension. | Albuminuria/Creatininuria ratio (mg/mmoL) at baseline. | Baseline. | 
| Intima media thickness > 0.9 mm rate in primary aldosteronism versus essential resistant hypertension. | Intima media thickness values (mm) evaluation with carotid Doppler ultrasound at baseline. | Baseline | 
| Chronic kidney disease in primary aldosteronism versus essential resistant hypertension. | Serum creatinine (mg/dL) at baseline. | Baseline. | 
| Aortic ectasia in primary aldosteronism versus essential resistant hypertension. | Aortic size (mm) determined with echocardiogram at baseline. | Baseline. | 
| Atrial fibrillation in primary aldosteronism versus essential resistant hypertension. | Electrocardiogram (ECG) at baseline. | Baseline. | 
| Insulin resistance in primary aldosteronism versus essential resistant hypertension. | Oral glucose tolerance test (OGTT) for determination of glucose (mg/dL) at time 0', 30', 60', 90' and 120' at baseline. | Baseline | 
| Insulin resistance in primary aldosteronism versus essential resistant hypertension. | Oral glucose tolerance test (OGTT) for determination of insulin (mg/dL) at time 0', 30', 60', 90' and 120' at baseline. | Baseline. | 
| Diabetes mellitus rate in primary aldosteronism versus essential resistant hypertension. | Oral glucose tolerance test (OGTT) for determination of glucose (mg/dL) at time 0' and 120' at baseline. | Baseline. | 
| Diabetes mellitus rate in primary aldosteronism versus essential resistant hypertension. | HbA1c (mmol/mol) at baseline. | Baseline. | 
| Sodium levels in primary aldosteronism versus essential resistant hypertension. | Serum Sodium (mmol/L) at baseline. | Baseline. | 
| Potassium levels in primary aldosteronism versus essential resistant hypertension. | Serum Potassium (mmol/L) at baseline. | Baseline. | 
| Oxidative stress in primary aldosteronism versus essential resistant hypertension. | Blood determination of 8-isoprostane (UI/L) at baseline. | Baseline. | 
| Oxidative stress in primary aldosteronism versus essential resistant hypertension. | Blood determination of total antioxidant capacity (UI/L) at baseline. | Baseline. | 
| Dyslipidemia in primary aldosteronism versus essential resistant hypertension. | Serum triglycerides (mg/dL) at baseline. | Baseline. | 
| Dyslipidemia in primary aldosteronism versus essential resistant hypertension. | Serum total-Cholesterol (mg/dL) at baseline. | Baseline. | 
| Dyslipidemia in primary aldosteronism versus essential resistant hypertension. | Serum HDL-Cholesterol (mg/dL) at baseline. | Baseline. | 
| Dyslipidemia in primary aldosteronism versus essential resistant hypertension. | Serum LDL-Cholesterol (mg/dL) at baseline. | Baseline. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Resistant Hypertension, Primary Aldosteronism, Renin-Angiotensin System, Blood Pressure, Cardiometabolic Risk, Early Atherosclerotic Damage, Oxidative Stress