Trial Outcomes & Findings for Renin-angiotensin-aldosterone System Polymorphisms in Resistant Hypertension and Adverse Cardiovascular Events (NCT NCT01173029)
NCT ID: NCT01173029
Last Updated: 2013-04-22
Results Overview
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.
COMPLETED
92 participants
up to 10 years
2013-04-22
Participant Flow
Recruitment was carried out in outpatient clinics at Instituto Nacional de Cardiologia.
Participants who have been diagnosed as secondary hypertension were excluded from the trial before assignment to resistant and pseudo-resistant groups.
Participant milestones
| Measure |
Resistant Arterial Hypertension
Subjects with systemic arterial hypertension in whom arterial pressure control was not achieved (24h ambulatory pressure monitoring: mean 24h systolic pressure \>/=130 mmHg and mean 24h 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.
|
Pseudo-resistant Arterial Hypertension
Subjects with systemic arterial hypertension in whom arterial pressure control was achieved (24h ambulatory pressure monitoring: mean 24h systolic pressure \<130 mmHg and mean 24h 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.
|
|---|---|---|
|
Overall Study
STARTED
|
61
|
31
|
|
Overall Study
COMPLETED
|
61
|
31
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Renin-angiotensin-aldosterone System Polymorphisms in Resistant Hypertension and Adverse Cardiovascular Events
Baseline characteristics by cohort
| Measure |
Resistant Arterial Hypertension
n=61 Participants
Subjects with systemic arterial hypertension in whom arterial pressure control was not achieved (24h ambulatory pressure monitoring: mean 24h systolic pressure \>/=130 mmHg and mean 24h 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.
|
Pseudo-resistant Arterial Hypertension
n=31 Participants
Subjects with systemic arterial hypertension in whom arterial pressure control was achieved (24h ambulatory pressure monitoring: mean 24h systolic pressure \<130 mmHg and mean 24h 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.
|
Total
n=92 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
50 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
70 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
11 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Age Continuous
|
52.3 years
STANDARD_DEVIATION 9.6 • n=5 Participants
|
56.8 years
STANDARD_DEVIATION 9.0 • n=7 Participants
|
54.4 years
STANDARD_DEVIATION 9.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
40 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Region of Enrollment
Brazil
|
61 participants
n=5 Participants
|
31 participants
n=7 Participants
|
92 participants
n=5 Participants
|
|
Renin-Angiotensin-Aldosterone System Polymorphism
Renin (G1051A) GG
|
22 participants
n=5 Participants
|
10 participants
n=7 Participants
|
32 participants
n=5 Participants
|
|
Renin-Angiotensin-Aldosterone System Polymorphism
Renin (G1051A) GA
|
24 participants
n=5 Participants
|
6 participants
n=7 Participants
|
30 participants
n=5 Participants
|
|
Renin-Angiotensin-Aldosterone System Polymorphism
Renin (G1051A) AA
|
15 participants
n=5 Participants
|
15 participants
n=7 Participants
|
30 participants
n=5 Participants
|
|
Renin-Angiotensin-Aldosterone System Polymorphism
ACE (I/D) II
|
12 participants
n=5 Participants
|
7 participants
n=7 Participants
|
19 participants
n=5 Participants
|
|
Renin-Angiotensin-Aldosterone System Polymorphism
ACE (I/D) ID
|
29 participants
n=5 Participants
|
13 participants
n=7 Participants
|
42 participants
n=5 Participants
|
|
Renin-Angiotensin-Aldosterone System Polymorphism
ACE (I/D) DD
|
20 participants
n=5 Participants
|
11 participants
n=7 Participants
|
31 participants
n=5 Participants
|
|
Renin-Angiotensin-Aldosterone System Polymorphism
Angiotensin II type 1 receptor (A1166C) AA
|
36 participants
n=5 Participants
|
26 participants
n=7 Participants
|
62 participants
n=5 Participants
|
|
Renin-Angiotensin-Aldosterone System Polymorphism
Angiotensin II type 1 receptor (A1166C) AC
|
24 participants
n=5 Participants
|
5 participants
n=7 Participants
|
29 participants
n=5 Participants
|
|
Renin-Angiotensin-Aldosterone System Polymorphism
Angiotensin II type 1 receptor (A1166C) CC
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Renin-Angiotensin-Aldosterone System Polymorphism
aldosterone synthase (C344T) CC
|
24 participants
n=5 Participants
|
9 participants
n=7 Participants
|
33 participants
n=5 Participants
|
|
Renin-Angiotensin-Aldosterone System Polymorphism
aldosterone synthase (C344T) TC
|
30 participants
n=5 Participants
|
15 participants
n=7 Participants
|
45 participants
n=5 Participants
|
|
Renin-Angiotensin-Aldosterone System Polymorphism
aldosterone synthase (C344T) TT
|
7 participants
n=5 Participants
|
7 participants
n=7 Participants
|
14 participants
n=5 Participants
|
|
Renin-Angiotensin-Aldosterone System Polymorphism
Angiotensinogen (M235T) TT
|
24 participants
n=5 Participants
|
6 participants
n=7 Participants
|
30 participants
n=5 Participants
|
|
Renin-Angiotensin-Aldosterone System Polymorphism
Angiotensinogen (M235T) MT
|
25 participants
n=5 Participants
|
15 participants
n=7 Participants
|
40 participants
n=5 Participants
|
|
Renin-Angiotensin-Aldosterone System Polymorphism
Angiotensinogen (M235T) MM
|
12 participants
n=5 Participants
|
10 participants
n=7 Participants
|
22 participants
n=5 Participants
|
|
Anti-hypertensive treatment
|
61 participants
n=5 Participants
|
31 participants
n=7 Participants
|
92 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: up to 10 yearsPopulation: Number of participants was based on input demand at outpatient clinics. Those who provided provided consent for genetic testing were included. A post-hoc sampling procedure (power calculation) validated sample size.
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.
Outcome measures
| Measure |
Resistant Arterial Hypertension
n=61 Participants
Subjects with systemic arterial hypertension in whom arterial pressure control was not achieved (24h ambulatory pressure monitoring: mean 24h systolic pressure \>/=130 mmHg and mean 24h 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.
|
Pseudo-resistant Arterial Hypertension
n=31 Participants
Subjects with systemic arterial hypertension in whom arterial pressure control was achieved (24h ambulatory pressure monitoring: mean 24h systolic pressure \<130 mmHg and mean 24h 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.
|
Polygenic Score: Two
Sum of the weights for analyzing polymorphisms equal to two.
|
Polygenic Score: Three
Sum of the weights for analyzing polymorphisms equal to three.
|
Polygenic Score: Four
Sum of the weights for analyzing polymorphisms equal to four.
|
Polygenic Score: Five
Sum of the weights for analyzing polymorphisms equal to five.
|
Polygenic Score: Six
Sum of the weights for analyzing polymorphisms equal to six.
|
Polygenic Score: Seven
Sum of the weights for analyzing polymorphisms equal to seven.
|
Polygenic Score: Eight
Sum of the weights for analyzing polymorphisms equal to eight.
|
|---|---|---|---|---|---|---|---|---|---|
|
Strokes, Either Fatal or Nonfatal
|
24 participants
|
7 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 10 yearsPopulation: Number of participants was based on input demand at outpatient clinics. Those who provided provided consent for genetic testing were included. A post-hoc sampling procedure (power calculation) validated sample size.
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.
Outcome measures
| Measure |
Resistant Arterial Hypertension
n=61 Participants
Subjects with systemic arterial hypertension in whom arterial pressure control was not achieved (24h ambulatory pressure monitoring: mean 24h systolic pressure \>/=130 mmHg and mean 24h 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.
|
Pseudo-resistant Arterial Hypertension
n=31 Participants
Subjects with systemic arterial hypertension in whom arterial pressure control was achieved (24h ambulatory pressure monitoring: mean 24h systolic pressure \<130 mmHg and mean 24h 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.
|
Polygenic Score: Two
Sum of the weights for analyzing polymorphisms equal to two.
|
Polygenic Score: Three
Sum of the weights for analyzing polymorphisms equal to three.
|
Polygenic Score: Four
Sum of the weights for analyzing polymorphisms equal to four.
|
Polygenic Score: Five
Sum of the weights for analyzing polymorphisms equal to five.
|
Polygenic Score: Six
Sum of the weights for analyzing polymorphisms equal to six.
|
Polygenic Score: Seven
Sum of the weights for analyzing polymorphisms equal to seven.
|
Polygenic Score: Eight
Sum of the weights for analyzing polymorphisms equal to eight.
|
|---|---|---|---|---|---|---|---|---|---|
|
Composite of Acute Myocardial Infarctions and/or Strokes Either Fatal or Nonfatal
|
34 participants
|
9 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
POST_HOC outcome
Timeframe: up to 10 yearsPopulation: Subjects in both resistant systemic arterial hypertension and pseudo-resistant systemic arterial hypertension groups had their respective genetic background scored according to present rule.
Among all analyzed, four renin-angiotensin-aldosterone polymorphisms had statistical significance relating to composite endpoint. They were: Angiotensinogen, renin, angiotensin II type 1 receptor and aldosterone synthase. Each polymorphism was arbitrarily weighted according to respective presentation in both alleles as follows: zero (low risk homozygosis), one (heterozygosis) and two (high risk homozygosis). In a following step, they were summed up for each subject, thus, creating a polygenic risk score. The weights of the polymorphisms were, thus, defined: 1. Angiotensinogen: MM - zero, MT - one, TT - two 2. Renin: AA - zero, GA - one, GG - two 3. Angiotensin II type 1 receptor: CC - zero, AC - one, AA - two 4. Aldosterone synthase: CC - zero, TC - one, TT - two The polygenic risk score value ranges from zero (all low risk polymorphisms in homozygosis) to eight (all high risk polymorphisms in homozygosis).
Outcome measures
| Measure |
Resistant Arterial Hypertension
n=1 Participants
Subjects with systemic arterial hypertension in whom arterial pressure control was not achieved (24h ambulatory pressure monitoring: mean 24h systolic pressure \>/=130 mmHg and mean 24h 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.
|
Pseudo-resistant Arterial Hypertension
n=1 Participants
Subjects with systemic arterial hypertension in whom arterial pressure control was achieved (24h ambulatory pressure monitoring: mean 24h systolic pressure \<130 mmHg and mean 24h 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.
|
Polygenic Score: Two
n=7 Participants
Sum of the weights for analyzing polymorphisms equal to two.
|
Polygenic Score: Three
n=14 Participants
Sum of the weights for analyzing polymorphisms equal to three.
|
Polygenic Score: Four
n=28 Participants
Sum of the weights for analyzing polymorphisms equal to four.
|
Polygenic Score: Five
n=21 Participants
Sum of the weights for analyzing polymorphisms equal to five.
|
Polygenic Score: Six
n=14 Participants
Sum of the weights for analyzing polymorphisms equal to six.
|
Polygenic Score: Seven
n=5 Participants
Sum of the weights for analyzing polymorphisms equal to seven.
|
Polygenic Score: Eight
n=2 Participants
Sum of the weights for analyzing polymorphisms equal to eight.
|
|---|---|---|---|---|---|---|---|---|---|
|
Polygenic Risk Score
|
0 composite enpoint events
|
0 composite enpoint events
|
1 composite enpoint events
|
3 composite enpoint events
|
17 composite enpoint events
|
10 composite enpoint events
|
8 composite enpoint events
|
3 composite enpoint events
|
2 composite enpoint events
|
Adverse Events
Resistant Arterial Hypertension
Pseudo-resistant Arterial Hypertension
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Paulo Robeto Benchimol Barbosa
Universidade Gama Filho
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place