Renin-angiotensin-aldosterone System Polymorphisms in Resistant Hypertension and Adverse Cardiovascular Events (GENHART)

This study has been completed.
Sponsor:
Collaborator:
Instituto Nacional de Cardiologia de Laranjeiras
Information provided by (Responsible Party):
Paulo Roberto Benchimol Barbosa, Universidade Gama Filho
ClinicalTrials.gov Identifier:
NCT01173029
First received: July 29, 2010
Last updated: April 13, 2013
Last verified: April 2013
  Purpose

Renin-angiotensin-aldosterone system (RAAS) polymorphisms influence 24h arterial pressure fluctuation. Resistant systemic arterial hypertension (RSAH) has an increased risk of end organ damage and unfavourable prognosis, whereas pseudo-RSAH usually respond favourably to drug therapy.

To prospectively investigate, in subjects with RSAH in a tropical South American city: 1) Adverse cardiovascular events defined as fatal and non-fatal stroke or acute myocardial infarction (AMI); and 2) the association of RAAS polymorphisms and adverse cardiovascular events in this population.

Study population: 212 hypertensives recruited from primary care assistance (time since first diagnosis of hypertension: 16.5±8.1 years) and without appropriate pressure control, between 2001 and 2006, corresponding to 0.48% of all hypertensives under care (18 new cases/year), 57±10 years old, 66% females. Under drug treatment schedule: three or more drugs including a diuretic. Ninety two randomly selected hypertensives basis had renin-angiotensin-aldosterone system genetic profile determined. Genetic assessment was carried out using a polymerase chain reaction assay amplification technique. The following single nucleotide polymorphisms were analyzed: renin (G1051A), angiotensinogen (M235T), angiotensin converting enzyme-ACE (I/D), angiotensin II type 1 receptor (A1166C), aldosterone synthase (C344T) and mineralocorticoid receptor (G3514C).


Condition Intervention
Systemic Arterial Hypertension
Hypertension Resistant to Conventional Therapy
Myocardial Infarction
Stroke
Drug: Anti-hypertensive drug treatment

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Observational Study of the Polymorphisms of the Renin-angiotensin-aldosterone System and Their Relation to Resistant Systemic Arterial Hypertension and Adverse Cardiovascular Events

Resource links provided by NLM:


Further study details as provided by Universidade Gama Filho:

Primary Outcome Measures:
  • Strokes, Either Fatal or Nonfatal [ Time Frame: up to 10 years ] [ Designated as safety issue: No ]

    Evidence of clinically definite stroke (focal neurological deficits persisting for more than 24 hours) confirmed or not by non-investigational computerized tomography.

    Death was considered to be related to the event if occurring up to 30 days after the acute event.

    Assessment twice an year by active and direct contact to patients or relatives and review of medical records.



Secondary Outcome Measures:
  • Composite of Acute Myocardial Infarctions and/or Strokes Either Fatal or Nonfatal [ Time Frame: up to 10 years ] [ Designated as safety issue: No ]

    Evidence of clinically definite stroke (focal neurological deficits persisting for more than 24 hours) confirmed or not by non-investigational computerized tomography.

    Evidence of clinically definite acute myocardial infarction (prolonged > 20min chest pain, not relieved by sublingual nitrate, ST-T segment deviation on 12-lead surface ECG, elevation of plasma troponin >0.2 ng/dL 6h following chest pain episode).

    Death was considered to be related to the event if occurring up to 30 days after the acute event.

    Assessment twice an year by active and direct contact to patients or relatives and review of medical records.



Enrollment: 92
Study Start Date: June 2001
Study Completion Date: December 2010
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Resistant Arterial Hypertension
Subjects with systemic arterial hypertension in whom arterial pressure control was not achieved (24hr ambulatory pressure monitoring: mean 24hr systolic pressure >/=130 mmHg or mean 24hr diastolic pressure >/=80mmHg) by non-investigation specialized hypertensive unit care, in spite of appropriate drug treatment regimen with three or more anti-hypertensive drugs including a diuretic. Anti-hypertensive drug treatment was non-investigational and was prescribed at discretion of the physician who performed primary evaluation.
Drug: Anti-hypertensive drug treatment
Anti-hypertensive drug treatment was non-investigational. Drug regimen, including which drug and the number of drugs prescribed, was left at discretion of the physician who carried primary assistance.
Other Names:
  • Thiazide Diuretics
  • Aldosterone receptor antagonist
  • Beta-blockers
  • ACE inhibitors
  • Angiotensin receptor blockers
  • Calcium channel blockers
Pseudo-resistant Arterial Hypertension
Subjects with systemic arterial hypertension in whom arterial pressure control was achieved (24hr ambulatory pressure monitoring: mean 24hr systolic pressure <130 mmHg and mean 24hr diastolic pressure <80mmHg) by non-investigation specialized hypertensive unit care, with appropriate drug treatment regimen with three or more anti-hypertensive drugs including a diuretic. Anti-hypertensive drug treatment was non-investigational and was prescribed at discretion of the physician who performed primary evaluation.
Drug: Anti-hypertensive drug treatment
Anti-hypertensive drug treatment was non-investigational. Drug regimen, including which drug and the number of drugs prescribed, was left at discretion of the physician who carried primary assistance.
Other Names:
  • Thiazide Diuretics
  • Aldosterone receptor antagonist
  • Beta-blockers
  • ACE inhibitors
  • Angiotensin receptor blockers
  • Calcium channel blockers

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Subjects of both genders in investigation for resistant systemic arterial hypertension at the Hypertension Unit, whose arterial pressure control was not achieved by primary care assistance despite regular use of three anti-hypertensive drugs, including one diuretic. All subjects received standard drug therapy, aiming at achieving outpatients clinics pressure <140/90mmHg and were re-evaluated up to four weeks later, including 24h ambulatory arterial pressure monitoring.

Criteria

Inclusion Criteria:

  • Subjects with uncontrolled systemic arterial hypertension despite use of three anti-hypertensive drugs, including one diuretic

Exclusion Criteria:

  • Secondary causes of systemic arterial hypertension
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01173029

Locations
Brazil
Instituto Nacional de Cardiologia
Rio de Janeiro, RH, Brazil, 22240-006
Sponsors and Collaborators
Universidade Gama Filho
Instituto Nacional de Cardiologia de Laranjeiras
Investigators
Principal Investigator: Paulo R Benchimol-Barbosa, MD, DSc Universidade Gama Filho
Principal Investigator: Priscilla Campos Universidade Gama Filho
Study Chair: José Barbosa-Filho, MD, DSc Universidade Gama Filho
Study Chair: Ivan Cordovil, MD Instituto Nacional de Cardiologia, Rio de Janeiro
  More Information

No publications provided

Responsible Party: Paulo Roberto Benchimol Barbosa, Head Researcher, Universidade Gama Filho
ClinicalTrials.gov Identifier: NCT01173029     History of Changes
Other Study ID Numbers: 0204/21.07.08
Study First Received: July 29, 2010
Results First Received: April 21, 2011
Last Updated: April 13, 2013
Health Authority: Brazil: Ethics Committee

Keywords provided by Universidade Gama Filho:
Systemic arterial hypertension
Hypertension Resistant to Conventional Therapy
Genetic polymorphisms
Renin-angiotensin-aldosterone system genetic polymorphism
Risk markers
Adverse events
Acute myocardial infarction
Stroke

Additional relevant MeSH terms:
Hypertension
Infarction
Myocardial Infarction
Stroke
Vascular Diseases
Cardiovascular Diseases
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Angiotensin-Converting Enzyme Inhibitors
Antihypertensive Agents
Calcium Channel Blockers
Diuretics
Sodium Chloride Symporter Inhibitors
Angiotensin Receptor Antagonists
Aldosterone Antagonists
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Membrane Transport Modulators
Natriuretic Agents

ClinicalTrials.gov processed this record on April 15, 2014