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

Completed

Conditions: Systemic Arterial Hypertension
Hypertension Resistant to Conventional Therapy
Myocardial Infarction
Stroke

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).

Recruitment & Eligibility

Inclusion Criteria

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

Exclusion Criteria

Arm && Interventions

Group	Intervention	Description
Resistant Arterial Hypertension	Anti-hypertensive drug treatment	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.
Pseudo-resistant Arterial Hypertension	Anti-hypertensive drug treatment	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.

Primary Outcome Measures

Name	Time	Method
Strokes, Either Fatal or Nonfatal	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

Name	Time	Method
Composite of Acute Myocardial Infarctions and/or Strokes Either Fatal or Nonfatal	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.