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Vascular morphological and functional impairments
in symptom-free, non-treated hypertensive
patients
László Csiba1, Katalin Réka Kovács2,
Csilla-Cecília Szekeres2, Zoltán Bajkó2,
Krisztina Csapó1, Sándor Molnár1, László Oláh1,
Mária Tünde Magyar1, Dániel Bereczki3,
Renáta Laczik4, Pál Soltész4, László Kardos5
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
Abstract
Introduction Purpose
Complex assessment of morphological and
hemodynamical alterations in early stage
hypertensive patients
untreated hypertension
Background Chronic hypertension (HT) results in
morphological and functional changes in the
vessels. Our aim was to verify these initial
subclinical alterations in early stage
hypertension. Methods The diagnosis of HT was
based on ambulatory blood pressure monitoring.
Diabetic patients were excluded and all HT
patients had normal CT. 78 HT patients (mean age
44,8/-10,1 years, male/female 0,85) were
compared with 85 age-matched controls (mean age
43,5/- 9,3 years, male/female 1). In both
groups blood tests, intima-media thickness (IMT)
and vascular stiffness parameters were measured.
Attention and memory skills, anxiety and
depression state were also determined by twelve
neuropsychological tests. Continuous,
non-invasive and simultaneous monitoring of
cerebral (MCA velocity) and cardiac
haemodynamical parameters were analyzed during
head-up tilt table testing (HUTT). Results No
significant differences were observed between the
blood values of the two groups. The IMT was
significantly thicker in the HT patients compared
to the control group (0,62/-0,11 mm vs.
0,54/-0,08 mm, plt0,0001). Significant
differences were also found in stiffness
parameters brachial augmentation index (AIx-br)
was -7,69/-29,63 in the HT group and
-21,23/-26,28 in the control group (p0,0031),
aortic pulse wave velocity (PWVao) was
10,06/-2,38 m/s in the HT group and 8,64/-1,96
m/s in the control group (plt0,0001). Alterations
of neuropsychological performances of HT patients
were also observed in some tests (WAIS Digit Span
Test-forward recall plt0,0001, WAIS Digit Symbol
Test plt0,0054). Anxiety was significantly more
often present in the HT patients. The results of
the parameters obtained by HUTT are under
evaluation. Conclusion Early morphological and
functional impairments of the CNS could be
detected in the symptom-free non-treated
hypertensive patients.
attention and memory deficit!
vascularremodelling
Stroke
recently diagnosed, untreated
hypertensive pts. 44.6 9.9 yrs male/female
0.9 n61
LVH fibrosis remodelling apoptosis
smoker diabetes
controls 45.39.5 yrs male/female 0.9n76
cardio- and cerebrovascular complications!
arrhythmia heart failure MI
death
LDL-cholesterollt3,4 mmol/Lgt
? glomerular filtration rate proteinuria/albuminu
ria glomerulosclerosis ? aldosterone release
renal failure
C n38
HTn25
hypertensive patients
healthy controls
vasoconstriction vascular hypertrophy endothelial
dysfunction atherosclerosis
hypertension thrombosis
?LDL n38
HT ?LDLn36
hyperlipidemic persons
hypertensive hyperlipidemic patients
Methods
Results

• ABPM (ambulatory blood pressure monitoring)
• blood tests (biochemistry, complete blood count,
  sedimentation rate, HbA1C, etc.)
• IMT - intima-media thickness common carotid
  arteries
• arterial stiffness (Arteriograph)
• HUTT - head-up tilt table testing (CNSystem Task
  Force Monitor)
• neuropsychological testing (memory, attention,
  reaction time, anxiety, depression)

Intima-media thickness - IMT
Flow mediated vasodilatation - FMD

• right and left common carotid arteries
• 6 measurement on each side ? mean

HT?LDL
C

NS
C
HT
0.650.1
0.610.1
0.560.7
6.15.2
0.540.8
p0.0126 p0.0085 p0.0009
5.60.7
5.05.5
5.15.5

C
?LDL
HT
HT?LDL
C
?LDL
HT
HT?LDL

?LDL
HT?LDL
Head-up tilt table testing - HUTT
Stiffness parameters
Parameters during HUTT
Pulse wave velocity - PWV
Augmentation index - AIx
supine position 10 (pretilt) supine position 10 (pretilt) p after tilt-up 10 (tilt) after tilt-up 10 (tilt) p
normotensive hypertensive normotensive hypertensive
HR - b/min 68.99.2 76.09.7 lt0.0001 79.715.5 86.412.1 0.0094
sBP - mmHg 117.69.9 136.017.5 lt0.0001 122.317.4 143.616.5 lt0.0001
dBP - mmHg 78.38.7 91.612.0 lt0.0001 85.912.8 100.812.0 lt0.0001
mBP - mmHg 89.68.9 103.812.4 lt0.0001 96.714.1 113.212.1 lt0.0001
CI - l/min/m2 2.99.2 2.90.86 NS 2.60.72 2.50.55 NS
SI - ml/m2 43.011.4 38.610.0 0.0209 32.47.5 29.15.6 0.0043
TPR -dyns/cm5 1377.8394.4 1577.6426.4 0.0143 1633.2463.8 1959.3411.9 0.0001
CBF_l - cm/s 60.725.5 58.126.0 NS 52.225.5 51.824.0 NS
CBF_r - cm/s 63.920.7 59.821.7 NS 55.620.4 52.122.5 NS
-10
10
9.7
12
ECG

0
m/s
elevated
high
normal
elevated
high
normal
oscillometric BP

C
HT?LDL
beat-to beat BP


HT
C
C
HT?LDL
10.02.0
9.82.5
ICG
9.12.6
8.111.5
-14.327.7
-28.423.4
-16.530.8
-8.125.2
TCD CBF
!

• continuous
• noninvazive
• simultaneous

10 tilt 10 supine 5
supine (pretilt) (posttilt)
CI cardiac indexSI stroke indexTPR total
peripheral resistance
HR heart ratesBP systolic blood pressure dBP
diastolic blood pressure mBP mean blood pressure
C
?LDL
HT
HT?LDL
C
?LDL
HT
HT?LDL
CBF_l cerebral blood flow - left MCACBF_r
cerebral blood flow - right MCA

p0.0012
p0.0016
p0.0003
ECG, beat-to beat blood pressure
ICG- Impedance cardiograph
TCD- Transcranial Doppler
Neuropsychological testing
Spielberger State Trait Anxiety Inventory
WAIS Digit Span Test
WAIS Digit Symbol Test

• State anxiety a transitory emotional response
  involving unpleasant feelings of tension and
  apprehensive thoughts.

• Personality trait of anxiety individual
  differences in the likelihood that a person would
  experience state anxiety in a stressful situation.

• Simple and Choice Reaction Time - reaction time
• Rey Auditory Verbal Learning Test - memory
  function
• Pieron Test - attention, spatial orientation,
  psychomotor tempo
• Trail Making Test - attention, visual searching,
  mental processing speed
• Digit Span Test - short-term memory, attention
• Block Design Test - visuospatial and motor skills
• Digit Symbol Test - attention, perceptual speed,
  motor speed, visual scanning and memory
• Spielberger State -Trait Anxiety Inventory -
  anxiety
• Beck Depression Inventory 21-question
  multiple-choice, self-report inventory

p0.0239

HT?LDL
C
HT?LDL
C
45.010.1
p0.0018
44.910.8
HT
C
ability to recall a sequence of numbers-
forward, backward -
the patient is given 90 sec to fill in as many
boxes as possible with the appropriate symbol
41.610.3
39.78.8
40.012.1
37.710.5
38.810.9

33.17.5

HT?LDL
C
C
HT?LDL
C
HT?LDL
?LDL
HT?LDL
?LDL
HT
C
HT
C
p0.0172

C
HT
HT
C
plt0.0001
11.82.1
53.410.3
Beck - Depression Inventory
50.49.1
11.62.6
47.110.3
score
9.51.9
score
9.21.6
NS
40.410.7
7.06.9
5.87.0
5.16.5
5.05.0
C
?LDL
HT
HT?LDL
C
?LDL
HT
HT?LDL
p0.0013
p0.0005
C
?LDL
HT
HT?LDL
HT
?LDL
HT?LDL
?LDL
p0.0006
HT?LDL
adjusted for age, gender, education
?LDL
Conclusions

• significantly ? intima-media thickness - IMT of
  common carotid arteries due to hypertension
• significantly ? stiffness parameters AIx and PWV
  in association with hypertension
• during HUTT remarkable differences in
  haemodynamical parameters (HR, sBP, dBP, mBP,
  TPR, SI, etc.) both in supine position and after
  tilt-up due to hypertension
• significantly lower neuropsychological
  performance in association with hypertension
  (i.e. Digit Span Test, Digit Symbol Test)
• significantly ? anxiety due to hypertension