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

Study Description

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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 or disease	Intervention/treatment
Systemic Arterial Hypertension; Hypertension Resistant to Conventional Therapy; Myocardial Infarction; Stroke	Drug: Anti-hypertensive drug treatment

Study Design

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Observational
Actual Enrollment :	92 participants
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
Study Start Date :	June 2001
Actual Primary Completion Date :	November 2009
Actual Study Completion Date :	December 2010

Groups and Cohorts

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort	Intervention/treatment
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

Outcome Measures

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Primary Outcome Measures :

1. Strokes, Either Fatal or Nonfatal [ Time Frame: up to 10 years ]

   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 :

1. Composite of Acute Myocardial Infarctions and/or Strokes Either Fatal or Nonfatal [ Time Frame: up to 10 years ]

   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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
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

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

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Publications of Results:

Benchimol Barbosa PR, Silva PC, Cordovil I, Barbosa-Filho J. Renin-angiotensin-aldosterone system polymorphisms in resistant hypertension and adverse cardiovascular events: GENHART-RIO Study. Eur Heart J 2010;31(suppl 1):243-243.

Benchimol-Barbosa PR, Silva PC, Cordovil I, Barbosa-Filho J. Renin-angiotensin-aldosterone system polymorphisms in resistant arterial hypertension: a genetic risk score for adverse cardiovascular events - GENHART-RIO study. Eur Heart J (2011) 32 (suppl 1): 103-103.

Campos PS, Benchimol-Barbosa PR, Cordovil I, Gomes-Filho JB, Tura BR. Polimorfismos do sistema renina-angiotensina-aldosterona na hipertensão arterial resistente e desfechos cardiovasculares adversos: Estudo GENHART-RIO. Arq Bras Cardiol; 2010. 95(3 supl. 1): 59-59

Campos FV, Benchimol-Barbosa PR, Vilela FD, Miranda CS, Gobbi GN, Barbosa-Filho J, Gondar AF, Barros MV, Lima AB, Cordovil I. Evaluation on the risk of target organ damage based on the genetic profile of AGT 235MT, mineralocorticoid receptor GCC5GG4C and ACE I/D in subjects with resistant hypertension. Circulation. 2008; 118:e223-e223.

Vilela FD, Benchimol-Barbosa PR, Zeno CC, Lima AB, Barros M, Campos FV, Miranda CS, Gobbi GN, Barbosa-Filho J, Cordovil I. The resistant hypertension genotypes of the population resident in Rio de Janeiro. Circulation. 2008; 118:e356-e357.

Benchimol-Barbosa PR, Varanda-Rosario AD, Rollin-Ornelas M, Vilela FD, Miranda CS, Gobbi GN, Barbosa-Filho J, Cordovil I. Aldosterone synthase C344T polymorphisms determine circadian arterial blood pressure variation in resistant systemic arterial hypertension. Circulation. 2008; 118:e398-e398.

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
First Posted:	July 30, 2010
Results First Posted:	March 6, 2013
Last Update Posted:	April 22, 2013
Last Verified:	April 2013

Keywords provided by Paulo Roberto Benchimol Barbosa, 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; Coronary Vasospasm; Vascular Diseases; Cardiovascular Diseases; Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Coronary Disease	Diuretics; Calcium Channel Blockers; Antihypertensive Agents; Angiotensin Receptor Antagonists; Mineralocorticoid Receptor Antagonists; Natriuretic Agents; Physiological Effects of Drugs; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Diuretics, Potassium Sparing