Omics Signature in the Diagnosis of Hypertension

Study Overview
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Brief Summary
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The purpose of this study is to assess the validity and usefulness of omics signatures for improved identification and risk stratification of patients with endocrine hypertension and stratification of patients with primary hypertension.

Detailed Description
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Arterial hypertension is the most important cause of death in the world. At referral hypertension centers about 25% of patients have a single cause for hypertension, so-called secondary hypertension, mostly of endocrine, adrenal origin (primary aldosteronism, pheochromocytoma/ paraganglioma, Cushing's syndrome). This rate steps up to 50% in patients with drug resistant hypertension. Proper treatment of secondary hypertension improves prognosis considerably but depends on adequate diagnosis. Classically the diagnosis of such forms of hypertension rests on cumbersome biochemical and imaging procedures that may not completely take away uncertainty. Modern '-omics' techniques (genomics, metabolomics, proteomics of plasma and urine) may allow faster and better diagnosis. In addition, they may provide a basis for stratification of hypertensive patients that do not have a identifiable cause of hypertension, so-called primary hypertension. This stratification may help predicting response to antihypertensive drugs and determining prognosis and thus, help to establish personalized medicine in hypertension care.

Official Title
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Performance of an Omics-signature in the Diagnosis and Prognosis of Endocrine and Primary Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Other: omics


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged from 18 to 75 years old A signed and dated informed consent form A diagnosis of hypertension defined either as: Use of antihypertensive drug (s) Arterial hypertension: in untreated patients this must be confirmed by daytime ambulatory blood pressure monitoring (ABPM), or home blood pressure monitoring, with blood pressure higher or equal to 135 mmHg for systolic blood pressure and/or higher or equal to 85 mmHg for diastolic blood pressure. In order to be eligible to participate in the nested case control study, a subject must also meet the following criteria: - A conformed diagnosis of PA, PPGL or CS for case patients and PHT (exclusion of secondary forms) for their matched counterparts Exclusion Criteria: Any severe comorbid conditions that, according to the attending physician, could decrease the life expectancy to less than 3 years Any active malignancy unrelated to adrenal disease or PPGL Guardianship for incapacity A potential control subject who meets any of the following criteria will be excluded from participation in the nested case controlled study in case of: Existence of any other forms of secondary hypertension such as renal artery stenosis, renal disease, Munchausen's syndrome in which the patient induces hypertension regardless of method. Drug-induced (included factitious use of illicit substances) hypertension

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hypertensive patients<br>Diagnostic procedures in patients with hypertension applying omics results | Other: omics<br>* diagnostic procedures applying omics results<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sensitivities of omics signatures for the diagnosis of subtypes of hypertension | The proportion of patients with various subtypes of endocrine hypertension as identified by omics signature in patients in which subtypes have been identified by usual diagnostic algorithms | 1 year | 
| specificities of omics signatures for the diagnosis of subtypes of hypertension | The proportion of patients with non-endocrine hypertension as identified by omics signature in patients identified as having non-endocrine hypertension by usual diagnostic algorithms. | 1 year | 
| positive likelihood ratio | positive likelihood ratios of omics signatures for the diagnosis of subtypes of hypertension | 1 year | 
| negative likelihood ratio | negative likelihood ratios of omics signatures for the diagnosis of subtypes of hypertension | 1 year | 
| positive predictive value | positive predictive values of omics signatures for the diagnosis of subtypes of hypertension | 1 year | 
| negative predictive value | negative predictive values of omics signatures for the diagnosis of subtypes of hypertension | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of major adverse cardiovascular events (MACE) | death, myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) or need for them, cerebrovascular accident (CVA), hospitalization for acute decompensated heart failure | within 12 months after baseline | 
| Left ventricular mass as assessed by echocardiography | Left ventricular mass index measured by ultrasound imaging | 1 year | 
| Costs | Questionnaires on costs of evaluation, costs of misdiagnosis | 1 year | 
| Ambulatory blood pressure measurement (ABPM) | ABPM | 1 year | 
| microalbuminuria | albumin-creatinine ratio in urine | 1 year | 
| atrial fibrillation | atrial fibrillation as assessed by EKG | 1 year | 
| RAND-36 | Quality of life assessment by the RAND-36 questionnaire | 1 year | 
| EQ5D | Quality of life assessment by the EQ5D questionnaire | 1 year | 
| Hospital Anxiety and Depression Scale (HADS) | Assessment of anxiety and depression by the HADS questionnaire | 1 year | 
| Cognitive Functioning Questionnaire (CFQ) | Assessment of cognitive functioning by CFQ | 1 year | 
| Montreal Cognitive Assessment (MOCA) | Assessment of cognitive functioning by MOCA | 1 year | 
| Home blood pressure measurement (HBPM) | HBPM | 1 year | 
| number of antihypertensive drugs | number of antihypertensive drugs | 1 year | 
| defined daily dosages | defined daily dosages of antihypertensive drugs | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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genomics, proteomics, metabolomics, endocrine hypertension, primary aldosteronism, Cushing syndrom, pheochromocytoma