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

Stroke Clinical Trial

— GENHART  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01173029
• Other study ID #: 0204/21.07.08
• Status: Completed
• Phase: N/A
• First received: July 29, 2010
• Last updated: April 13, 2013
• Start date: June 2001
• Est. completion date: December 2010

Study information

• Verified date: April 2013
• Source: Universidade Gama Filho
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Observational

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: December 2010
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Coronary Vasospasm
• Hypertension
• Hypertension Resistant to Conventional Therapy
• Infarction
• Myocardial Infarction
• Stroke
• Systemic Arterial Hypertension

Intervention

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.

Locations

Country	Name	City	State
Brazil	Instituto Nacional de Cardiologia	Rio de Janeiro	RH

Sponsors (2)

Lead Sponsor	Collaborator
Universidade Gama Filho	Instituto Nacional de Cardiologia de Laranjeiras

Country where clinical trial is conducted

Brazil, 

References & Publications (6)

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)

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 hyperte

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

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.

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Strokes, Either Fatal or Nonfatal	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.	up to 10 years	No
Secondary	Composite of Acute Myocardial Infarctions and/or Strokes Either Fatal or Nonfatal	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.	up to 10 years	No