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

NCT01173029 | Completed Results

• 1 other identifier: 0204/21.07.08
• Study Type: observational
• Target: 92
• Locations: 1 country
• Sites: 1

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).

Conditions

Systemic Arterial Hypertension; Hypertension Resistant to Conventional Therapy; Myocardial Infarction; Stroke

Keywords

Systemic arterial hypertension; Hypertension Resistant to Conventional Therapy; Genetic polymorphisms; Renin-angiotensin-aldosterone system genetic polymorphism; Risk markers; Adverse events; Acute myocardial infarction; Stroke

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Composite of Acute Myocardial Infarctions and/or Strokes Either Fatal or Nonfatal

  up to 10 years

Study Arms (2)

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

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

Interventions

Anti-hypertensive drug treatment DRUG

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.

Also known as: Thiazide Diuretics, Aldosterone receptor antagonist, Beta-blockers, ACE inhibitors, Angiotensin receptor blockers, Calcium channel blockers

Pseudo-resistant Arterial Hypertension; Resistant Arterial Hypertension

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• Secondary causes of systemic arterial hypertension

Sponsors & Collaborators

• Universidade Gama Filho: lead
• Instituto Nacional de Cardiologia de Laranjeiras: collaborator

Study Sites (1)

Instituto Nacional de Cardiologia

Rio de Janeiro, RH, 22240-006, Brazil

Location

Related 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.

  RESULT

• 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.

  RESULT

• 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

  RESULT

• 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.

  RESULT

• 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.

  RESULT

• 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.

  RESULT

MeSH Terms

Conditions

Hypertension; Hypertension Resistant to Conventional Therapy; Myocardial Infarction; Stroke

Interventions

Sodium Chloride Symporter Inhibitors; Mineralocorticoid Receptor Antagonists; Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Calcium Channel Blockers

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Myocardial Ischemia; Heart Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Diuretics; Natriuretic Agents; Physiological Effects of Drugs; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Diuretics, Potassium Sparing; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Protease Inhibitors; Enzyme Inhibitors; Calcium-Regulating Hormones and Agents; Cardiovascular Agents; Therapeutic Uses

Limitations and Caveats

Drugs prescribed were at the discretion of attending physician. The impact of anti-hypertensive drugs on the outcomes was not assessed.

Results Point of Contact

• Title: Paulo Robeto Benchimol Barbosa
• Organization: Universidade Gama Filho

ecgar@yahoo.com

+55-21-95320182

Study Officials

• Paulo R Benchimol-Barbosa, MD, DSc

  Universidade Gama Filho

  PRINCIPAL INVESTIGATOR

• Priscilla Campos

  Universidade Gama Filho

  PRINCIPAL INVESTIGATOR

• José Barbosa-Filho, MD, DSc

  Universidade Gama Filho

  STUDY CHAIR

• Ivan Cordovil, MD

  Instituto Nacional de Cardiologia, Rio de Janeiro

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head Researcher

Study Record Dates

• First Submitted: July 29, 2010
• First Posted: July 30, 2010
• Study Start: June 1, 2001
• Primary Completion: November 1, 2009
• Study Completion: December 1, 2010
• Last Updated: April 22, 2013
• Results First Posted: March 6, 2013

Record last verified: 2013-04

Locations

BR (1)