G.N. Dalekos3, M. Elisaf2, A.I. Hatzitolios1 ASSOCIATION OF CIRCADIAN BLOOD PRESSURE AND HEART RATE PATTERNS WITH SEVERITY OF ACUTE ISCHEMIC STROKE: PRELIMINARY RESULTS N. Kakaletsis1, H. Milionis2, G. Ntaios3, C. Savopoulos1, K. Makaritsis3, K. Tziomalos1, G.N. Dalekos3, M. Elisaf2, A.I. Hatzitolios1 First Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece Department of Medicine, University of Ioannina, Ioannina, Greece Department of Medicine, University of Thessaly, Larissa, Greece LARISSA  21 March 2015

Introduction - Aim The association of blood pressure (BP) levels following acute ischemic stroke (AIS) with outcome still remains controversial. BP is increased in up to 75% to 80% of patients with acute stroke and usually decreases spontaneously over the next few days. 1-3 Data from a number of studies suggest that high BP in the acute stroke period is associated with a poor short-term outcome, but in other studies the opposite has been reported. 4-7 Recently, ambulatory 24-hour BP monitoring (ABPM) which allows the more precisely observation of a rapidly evolving phenomenon such as the BP course in the acute stage of stroke, has been used. Our purpose is to study the relationship between BP course in the acute phase of stroke by ambulatory 24-hour BP monitoring (ABPM) and stroke severity assessed with the National Institutes of Health Stroke Scale (NIHSS). 1. Wallace et al, JAMA 1981 2. Britton et al, Stroke 1986 3. Toyoda et al, Stroke 2006 4. Lawes et al, Stroke 2004 5. Robinson et al, Cerebrovasc Dis 1997 6. Allen et al, J Neurol Neurosurg Psychiatry 1984 7. Jorgensen et al, Lancet 1994

Methods Inclusion Criteria: Exclusion Criteria: Known stroke risk factors and clinical findings on admission were recorded. ABPM every 20 min within 24 hours of hospital admission automated oscillometric device (TM 2430, A&D Company Ltd) Day-time; 7:00-22:59 Night-time; 23:00-6:59 Definitions; Minor AIS: NIHSS ≤4 Moderate/severe AIS: NIHSS>4 Analysis of parameters derived by ABPM was made by BP analysis software; Doctor Pro 3 (A&D Company Ltd) Statistical analysis for continuous data (mean ± standard deviation) was made by Student's T-test, while for non-continuous data (numbers and percentages) chi-square test was used. IBM SPSS Statistics for Windows, Version 21.0 Blood Pressure Variability in Acute Ischemic Stroke (PREVISE study) NCT01915862 Inclusion Criteria: Acute ischemic stroke Admission within 24 after the onset of symptom Exclusion Criteria: Transient ischemic attack Intracerebral hemorrhage Subarachnoid hemorrhage Cerebral sinus venous thrombosis Stroke mimics Late admission (>24 hours after stroke onset) The protocol has been approved by Bioethics Committee of Medical School of Aristotle University of Thessaloniki and local University Hospital Scientific Committees

Clinical characteristics and known stroke risk factors on admission Variables Population (n=22) NIHSS≤4 (n=9) NIHSS>4 (n=13) p Pre-Stroke mRS>2 18 (81.8%) 7 (77.8%) 11 (84.6%) 1.000 NIHSS admission 9.9 (9.1) 2.3 (1.1) 15.2 (8,5) <0.001 Age (years) 79.3 (7) 77.8 (5.6) 80.4 (7.9) 0.404 Male gender 12 (54.5%) 6 (66.7%) 6 (46.2%) 0.342 Cerebrovascular Disease 6 (27.3%) 3 (33.3%) 3 (23.1%) 0.595 Hypertension 19 (86.4%) 8 (88.9%) Dyslipidemia 15 (68.2%) 8 (61.5%) 0.421 Diabetes Mellitus 8 (36.4%) 2 (22.2%) 0.251 Atrial Fibrillation 1 (11.1%) 7 (53.8%) 0.040 Smoking Coronary artery Disease 5 (22.7%) 4 (30.8%) 0.279 Congestive Heart Failure 3 (13.6%) 0 (0%) 0.240 Body Mass Index 29.4 (5.1) 29.6 (5) 29.4 (5.3) 0.927 Statistical analysis for continuous data (mean ± standard deviation) was made by Student’s T-test, while for non-continuous data (numbers and percentages) chi-square test was used.

Parameters derived by 24-h ABPM Variables Population (n=22) NIHSS≤4 (n=9) NIHSS>4 (n=13) p Systolic 24h SBP 147.7 (17.7) 143.8 (14) 149.6 (20) 0.460 Mean day SBP 147.4 (16.9) 144,8 (14.7) 149.2 (18.7) 0.557 Mean night SBP 146.5 (22.2) 140 (16.8) 150.9 (24.9) 0.266 p (day/night) 0.715 0.284 0.607 - Diastolic 24h DBP 77.4 (11) 74.1 (11.7) 79.7 (11.7) 0.251 Mean day DBP 78.1 (11) 75.2 (9.9) 80.2 (11.6) 0.313 Mean night DBP 75.1 (11.8) 70.1 (8.8) 78.6 (12.6) 0.097 0.033 0.009 0.438 Mean 24h MBP 100.3 (12.7) 96.9 (10.5) 102.7 (13.9) 0.303 Mean day MBP 100.9 (12.5) 98 (11.3) 102.8 (13.4) 0.386 Mean night MBP 98.6 (14.6) 93.1 (10.8) 102.5 (16) 0.142 0.159 0.060 0.849 Heart Rate 24h HR 72.7 (13.7) 63.9 (6.8) 79.1 (13.9) 0.003 Mean day HR 73.2 (12.6) 65.4 (6.9) 78.5 (13) 0.006 Mean night HR 72.7 (17.4) 60.2 (7.5) 81.3 (17.1) 0.001 0.771 0.250 SBP: Systolic BP (mmHg), DBP: Diastolic BP (mmHg), MBP: Mean BP = DBP + Pulse Pressure/3 (mmHg), HR: Heart rate (bpm) Conclusions Lower values of DBP (dipping pattern) and HR during night in AIS patients derived by ABPM are associated with minor AIS. Furthermore, higher HR values during 24h are associated with moderate/severe AIS.