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Morphological, cerebral haemodynamic and neuropsychological changes before and after ACEI therapy

Katalin Réka Kovács2, Csilla-Celília Szekeres2, Zoltán Bajkó2, Krisztina Csapó1, Sándor Molnár1, László Oláh1, Mária Tünde Magyar1, Dániel Bereczki3, Renáta Laczik4, Pál Soltész4,

László Kardos5, László Csiba1

1Department of Neurology, University Of Debrecen Medical and Health Science Center, Debrecen, Hungary, 2Department of Neurology, Mures County Clinical Emergency Hospital, Targu-Mures, Romania, 3Department of Neurology, Semmelweis University  Budapest, Hungary, 43rd Department of Medicine, Institute for Internal Medicine, University Of Debrecen Medical and Health Science Center, Debrecen, Hungary, 5Contract medical statistician, Debrecen, Hungary

Introduction

Methods

Results

Conclusions

AbstractBackground: Hypertension (HT) is one of the major risk factors of stroke. The early diagnosis and treatment of impairments caused by HT is essential for effective stroke prevention. We investigated the morphological and functional alterations affecting cardio- and cerebrovascular parameters in HT patients before and after antihypertensive therapy. 41 HT patients were included (mean age: 47,5+/-8,4 years, male/female: 0,78), none of them suffered from diabetes. All HT patients had normal CT. The results before and after 6 and 12 months ACEI therapy were compared. Methods: The diagnosis of HT was based on ambulatory blood pressure monitoring. Blood tests, intima-media thickness (IMT) and stiffness parameters were measured. By head-up tilt table testing (HUTT) continuous non-invasive cerebral blood velocity was measured in bilateral MCA with simultaneous monitoring of beat-to-beat BP changes. Twelve neuropsychological tests (attention, memory, depression etc.) were also performed.Results: After six months ACEI therapy the BP values significantly reduced in 57,7% of patients (BPsys: p=0,0013, BPdia: p=0,018). The patients were divided into two groups (well and poorly controlled BP) based on BP monitoring. 6 months antihypertensive therapy resulted in non significant IMT reduction in both groups (6%). Vessel stiffness parameters (augmentation index [AIx] and pulse wave velocity [PWV)]) improved in both groups after therapy, but in the well controlled group more drastic reduction of AIx and PWV was observed compared to the poorly controlled group (PWV reduction 7,8% vs. 1,2%). During HUTT significant differences were observed between the baseline and 6 months BP values in the well controlled group (BPdia: p=0,01), while during the HUTT the BP of poorly controlled patients remained significantly worse compared to well treated ones (p=0,01). Conclusions: The improvement of hemodynamic parameters could be detected already after 6 months therapy if the BP was well controlled.

many cardiovascular & cerebrovascular parameters

• intima media thickness – IMT ↑• impaired endothelial dysfunction• impaired elasticity and vasoreactivity of cerebral and peripheral vessels• altered autonomic nervous system activity (baroreflex sensitivity, heart rate variability, total peripheral resistance etc.)

hypertension compromise

Purposeto evaluate morphological and functional alterations through cardio- and

cerebrovascular parameters in hypertensive patients before and after antihypertensive therapy

Patients

- no diabetes- normal cerebral CT scan

41 HT patients47.5 ± 8.4 years

male/female: 0.78

therapy with ACEI

baseline examination

25 HT patients46.9±10.0 yearsmale/female: 1.5

control after 1 year of antihypertensive therapy

well controlled HTN=13

poorly controlled HTN=12

ABPM

• ambulatory blood pressure monitoring – ABPM

• intima-media thickness – IMT: - common carotid arteries - 6 measurements on each side

• flow mediated vasodilatation - FMD

• arterial stiffness: - augmentation index - AIX - pulse wave velocity - PWV

- pulse pressure - PP

• head-up tilt table testing – HUTT

- beat-to-beat blood pressure- 3 leads electrocardiogram (ECG)- bilateral blood flow velocities in middle cerebral

arteries, measured by Transcranial Doppler (TCD) - stroke volumen (SV)

- cardiac output (CO) - total peripheral resistance (TPR) - baroreflex sensitivity

- heart rate variability

continous, noninvasive, simultaneous registration of:

impedance cardiography(ICG)

• neuropsychological testing

→ 10 minutes of resting phase → passive tilt upright to an angle of 70° for 10 min. → returned to the supine position for another 5 min.

- 12 neuropsychological tests: reaction time, memory function, attention, perceptual speed, motor speed, visual scanning, anxiety, depression

Trail Making Test WAIS Digit Span Test WAIS Block Design Test WAIS Digit Symbol Test

• intima media thickness ↓ after 12 months; in the well controlled HT group compared to the poorly controlled one IMT was nonsignificantly lower after ACEI therapy• flow mediated dilatation ↑ by 18.4% in well controlled HT group , and ↓ by 23.0% in poorly controlled HT patients after 12 months of therapy• nonsignificanty ↓ stiffness parameters in well controlled HT patients after therapy • significantly higher blood pressure values (dBP, mBP) during HUTT in poorly controlled HT patients; after tilt-up nonsignificant ↑ of TPRI and significant ↓ of stroke index and cardiac index in poorly controlled HT patients • nonsignificant differencies in neuropsychological perfomance between the well and poorly controlled HT patients

ABPM - Ambulatory bood pressure monitoring

IMT – intima media thickness

FMD – flow mediated dilatation

Arterial stiffness

Augmentation index -AIx Pulse wave velocity - PWV

HUTT – head-up tilt table testing

Neuropsychological testingCognitive performance difference 95% CI p

Simple Reaction Time 0.055 -0.004 - 0.114 0.067

Choice Reaction Time 0.051 -0.015 - 0.118 0.123

Rey Auditory Verbal Learning -1.492 -3.356 - 0.371 0.109

First Recognition -0.432 -1.667 - 0.802 0.473

Trail Making Test 0.519 -5.886 - 6.924 0.867

WAIS Digit Span Test -0.926 -3.091 - 1.238 0.382

WAIS Block Design Test -2.011 -4.141 - 0.118 0.062

WAIS Digit Symbol Test 2.390 -2.549 - 7.330 0.322

Difference between well vs. poorly controlled HT patients at the 12 months into treatment adjusted for baseline values of the different tests and age

Anxiety and depression difference 95% CI p

Spielberger State Anxiety Inventory 2.260 -4.680 - 9.201 0.502

Spielberger Trait Anxiety Inventory -1.273 -9.235 - 6.687 0.740

Beck Depression Inventory -1.579 -8.819 - 5.660 0.654

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well controlled HT poorly controlled HT

mmHg

mmHgmmHg

mmHg

Normal values<130/80 mmHg: daytime - active period: (06.00-22.00)<120/70 mmHg: nighttime - passive period: (22.00-06.00)

• sBP: systolic blood pressure• dBP: diastolic blood pressure

Daytime Daytime

Nighttime Nighttime

137.0±12.7

84.5±9.9

122.7±6.5

75.3±6.1

p=0.0032

p=0.0030

baseline after 1 year of therapy baseline after 1 year of therapy

baseline after 1 year of therapy baseline after 1 year of therapy

123.4±17.5

73.2±12.5

109.1±8.8

64.4±6.6

p=0.0161

p=0.0496

144.9±7.9

91.2±5.8

142.1±6.7

90.4±6.2

122.6±9.9

74.2±7.2

124.5±10.9

75.9±7.1

baseline after 1 year of ACEI therapy

0.65±0.11 0.62±0.11 difference between well vs. poorly

controlled HT at 12 months into treatment adjusted for baseline values of the IMT and

age: -0.031

• the percentual change of the brachial artery diameter from rest to the diameter at 60 second after ischaemia cuff release

• it may be reduced by factors such as aging and hypertension

baseline after 1 year of ACEI therapy

4.3±1.0

5.1±1.7

baseline 1 year control

7.8±1.9

6.0±1.8

18.4% ↑

23.0% ↓

well controlled HT

poorly controlled HT

%

%

Values of stiffness parameters

Aix (%) PWV (m/s)

optimal < -30 < 7

normal -30 → 10 7 → 9.7

increased -10 → 10 9.7 →12

high >10 >12

Difference between well vs. poorly controlled HT at 12 months into treatment adjusted for baseline values and age

-21.46 % -1.12 m/s

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Total peripheral resistance index - TPRI Sroke index - SI Cardiac index - CI

well controlled HT poorly controlled HTwell controlled HT poorly controlled HTwell controlled HT poorly controlled HT

Differences between well vs. poorly controlled HT patients at the 12 months into treatment adjusted for baseline values of different parameters , gender and age

supine supinetilt-up tilt-up supine supinetilt-up tilt-up supine supinetilt-up tilt-up

19.75% 28.08 %

21.14 %32.33 %

p=0.0131p=0.0035

8.97 %

19.50 %

• during HUTT significant differences in dBP (p= 0.0403) and mBP (p=0.0487) values between well vs. poorly controlled HT patients in supine position (adjustment for baseline values and age)

SV: amount of blood which the left ventricle ejects into the aorta with each heartbeat (ml). SI: is indexed to the Body Surface Area (BSA) of the patient (ml/m2).CO: the circulating blood volume per minute (L/min). CO:SV x HR. CI: is indexed to the BSA of a patient (L/min/m2).TPR: is the resistance of small and large vessels against which the left ventricle is pomping the blood (dyn*sec/cm5). TPRI is indexed to the BSA of the patient. (dyn*sec/cm5/m2).

Physiological reaction in response to orthostatic stress

HR ↑ by 10-20 bpm sBP↓ by 0-10 mmHg dBP ↑ by 5-10 mmHg

SV ↓ up to 35% CO ↓ up to 20% TPR ↑ up to 25%

sBP dBP sBP dBP

sBP dBPsBP dBP sBP dBPsBP dBP

sBP dBPsBP dBP

6.0±1.1 5.6±1.2

N=25

N=25