1. Morphological, cerebral haemodynamic and neuropsychological changes before and after ACEI therapy Katalin Réka Kovács 2, Csilla-Celília Szekeres 2, Zoltán Bajkó 2, Krisztina Csapó 1, Sándor Molnár 1, László Oláh 1, Mária Tünde Magyar 1, Dániel Bereczki 3, Renáta Laczik 4, Pál Soltész 4, László Kardos 5, László Csiba 1 1 Department of Neurology, University Of Debrecen Medical and Health Science Center, Debrecen, Hungary, 2 Department of Neurology, Mures County Clinical Emergency Hospital, Targu-Mures, Romania, 3 Department of Neurology, Semmelweis University Budapest, Hungary, 4 3rd Department of Medicine, Institute for Internal Medicine, University Of Debrecen Medical and Health Science Center, Debrecen, Hungary, 5 Contract medical statistician, Debrecen, Hungary Introduction Methods Results Conclusions Abstract Background: 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 Purpose to 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 patients 47.5 ± 8.4 years male/female: 0.78 therapy with ACEI baseline examination 25 HT patients 46.9±10.0 years male/female: 1.5 control after 1 year of antihypertensive therapy well controlled HT N=13 poorly controlled HT N=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 TestWAIS 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 -AIxPulse wave velocity - PWV HUTT – head-up tilt table testing Neuropsychological testing Cognitive performance difference95% CIp Simple Reaction Time 0.055-0.004 - 0.1140.067 Choice Reaction Time 0.051-0.015 - 0.1180.123 Rey Auditory Verbal Learning -1.492-3.356 - 0.3710.109 First Recognition -0.432-1.667 - 0.8020.473 Trail Making Test 0.519-5.886 - 6.9240.867 WAIS Digit Span Test -0.926-3.091 - 1.2380.382 WAIS Block Design Test -2.011-4.141 - 0.1180.062 WAIS Digit Symbol Test 2.390-2.549 - 7.3300.322 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 difference95% CIp Spielberger State Anxiety Inventory 2.260-4.680 - 9.2010.502 Spielberger Trait Anxiety Inventory -1.273-9.235 - 6.6870.740 Beck Depression Inventory -1.579-8.819 - 5.6600.654 well controlled HT poorly controlled HT 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 Nighttime 137.0 ±12.7 84.5 ±9.9 122.7 ±6.5 75.3 ±6.1 p=0.0032 p=0.0030 baselineafter 1 year of therapybaselineafter 1 year of therapy baselineafter 1 year of therapybaselineafter 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 baselineafter 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 baselineafter 1 year of ACEI therapy 4.3 ±1.0 5.1 ±1.7 baseline1 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 → 107 → 9.7 increased-10 → 109.7 →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 Total peripheral resistance index - TPRISroke index - SI Cardiac index - CI well controlled HTpoorly controlled HTwell controlled HTpoorly controlled HTwell controlled HTpoorly 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 tilt-up supine tilt-up supine tilt-up 19.75%28.08 % 21.14 % 32.33 % p=0.0131 p=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/m 2 ). CO: the circulating blood volume per minute (L/min). CO:SV x HR. CI: is indexed to the BSA of a patient (L/min/m 2 ). TPR: is the resistance of small and large vessels against which the left ventricle is pomping the blood (dyn*sec/cm 5 ). TPRI is indexed to the BSA of the patient. (dyn*sec/cm 5 /m 2 ). Physiological reaction in response to orthostatic stress HR ↑ by 10-20 bpmsBP↓ by 0-10 mmHgdBP ↑ by 5-10 mmHg SV ↓ up to 35%CO ↓ up to 20%TPR ↑ up to 25% sBP dBP sBP dBP sBP dBP sBP dBP sBP dBP sBP dBP sBP dBP sBP dBP 6.0 ±1.1 5.6 ±1.2 N=25