Clinical trial NCT01173029: Renin-angiotensin-aldosterone System Polymorphisms in Resistant Hypertension and Adverse Cardiovascular Events
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 type: OBSERVATIONAL
Overall status: COMPLETED
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
Lead sponsor: Universidade Gama Filho
Sponsor class: OTHER
Collaborators: name: Instituto Nacional de Cardiologia de Laranjeiras
First posted: 2010-07-30
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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).


Eligibility 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

Primary outcomes:
measure: Strokes, Either Fatal or Nonfatal
timeFrame: up to 10 years
Secondary outcomes:
measure: Composite of Acute Myocardial Infarctions and/or Strokes Either Fatal or Nonfatal
timeFrame: up to 10 years
Other outcomes:
Locations:
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Cardiologia
state: RH
Study officials:
affiliation: Universidade Gama Filho
name: Paulo R Benchimol-Barbosa, MD, DSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Universidade Gama Filho
name: Priscilla Campos
role: PRINCIPAL_INVESTIGATOR
affiliation: Universidade Gama Filho
name: José Barbosa-Filho, MD, DSc
role: STUDY_CHAIR
affiliation: Instituto Nacional de Cardiologia, Rio de Janeiro
name: Ivan Cordovil, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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
citation: 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.
citation: 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.
citation: 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.