Abstract

1. 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, p<0,0001). 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 (p=0,0031), 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 (p<0,0001). Alterations of neuropsychological performances of HT patients were also observed in some tests (WAIS Digit Span Test-forward recall p<0,0001, WAIS Digit Symbol Test p<0,0054). 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± 9.9yrs male/female: 0.9 n=61 LVH fibrosis remodelling apoptosis smoker diabetes controls45.3±9.5yrs male/female: 0.9n=76 cardio- and cerebrovascular complications! arrhythmia heart failure MI death LDL-cholesterol<3,4 mmol/L>  glomerular filtration rate proteinuria/albuminuria glomerulosclerosis  aldosterone release renal failure HTn=25 Cn=38 hypertensive patients healthy controls vasoconstriction vascular hypertrophy endothelial dysfunction atherosclerosis hypertension thrombosis HT+ ↑LDLn=36 ↑LDLn=38 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 0.65±0.1 0.61±0.1 0.56±0.7 6.1±5.2 0.54±0.8 *p=0.0126 **p=0.0085 ***p=0.0009 5.6±0.7 5.0±5.5 5.1±5.5 *** 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 -10 10 9.7 12 ECG % 0 m/s normal elevated high normal elevated high oscillometric BP *** C HT+↑LDL beat-to beat BP ** ** HT C C HT+↑LDL 10.0±2.0 9.8±2.5 ICG 9.1±2.6 8.11±1.5 -14.3±27.7 -28.4±23.4 -16.5±30.8 -8.1±25.2 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 C HT+↑LDL ↑LDL HT HT+↑LDL CBF_l: cerebral blood flow - left MCACBF_r: cerebral blood flow - right MCA **p=0.0012 **p=0.0016 ***p=0.0003 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 • Stateanxiety: a transitory emotional response involving unpleasant feelings of tension and apprehensive thoughts. • Personalitytrait 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 p=0.0239 *** HT+↑LDL HT+↑LDL C C 45.0±10.1 p=0.0018 HT 44.9±10.8 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 41.6±10.3 39.7±8.8 40.0±12.1 37.7±10.5 38.8±10.9 *** 33.1±7.5 *** C HT+↑LDL C HT+↑LDL C HT+↑LDL HT ↑LDL ↑LDL HT+↑LDL C HT C p=0.0172 *** C HT HT C ***p<0.0001 11.8±2.1 53.4±10.3 Beck - Depression Inventory 50.4±9.1 11.6±2.6 47.1±10.3 score 9.5±1.9 score 9.2±1.6 NS 40.4±10.7 7.0±6.9 5.8±7.0 5.1±6.5 5.0±5.0 C ↑LDL HT HT HT+↑LDL HT+↑LDL C ↑LDL p=0.0013 p=0.0005 ↑LDL HT HT+↑LDL C HT ↑LDL HT+↑LDL ↑LDL p=0.0006 HT+↑LDL adjusted for age, gender, education ↑LDL Conclusions • significantly ↑ intima-media thickness -IMT of common carotid arteries due tohypertension • 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