dissertations | 186 | Antti| 186 E Lindgren | Antti E Lindgren Eastern Finnish Saccular Intracranial Aneurysm Disease Saccular intracranial aneurysms Role of Type 2 Diabetes and Hypertension (sIAs) are balloon-like vascular Antti E Lindgren bulges that develop at branching Temporal Pattern of Incidence points of intacranial arteries in ap- Eastern Finnish Saccular Intracranial Aneurysm Disease - Role Type of 2 Diabetes and... proximately 3% of the population Eastern Finnish Saccular during life. The rupture of sIA wall is the most frequent cause of aneu- Intracranial Aneurysm rysmal subarachnoid hemorrhage (aSAH), a devastating form of stroke Disease that mainly affects the working-age population. This study is a part of the Role of Type 2 Diabetes and Hypertension long-term research effort of Kuopio sIA Database to characterize Eastern Temporal Pattern of Incidence Finnish sIA disease. In the present study, we used an overall cohort of 2904 consecutive sIA patients from 1980 to 2007 to analyze temporal pat- terns of aSAH incidence and the role of type 2 diabetes and hypertension in sIA disease. Publications of the University of Eastern Finland Dissertations in Health Sciences Publications of the University of Eastern Finland Dissertations in Health Sciences isbn 978-952-61-1203-9 ANTTI E LINDGREN Eastern Finnish Saccular Intracranial Aneurysm Disease Role of type 2 diabetes and hypertension Temporal pattern of incidence To be presented by permission of the Faculty of Health Sciences, University of Eastern Finland for public examination at Kuopio University Hospital Auditorium, Kuopio, on Friday, October 4th 2013, at 1 p.m. Publications of the University of Eastern Finland Dissertations in Health Sciences Number 186 Department of Neurosurgery, Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland Kuopio 2013 Kopijyvä Oy Kuopio, 2013 Series Editors: Professor Veli-Matti Kosma, M.D., Ph.D. Institute of Clinical Medicine, Pathology Faculty of Health Sciences Professor Hannele Turunen, Ph.D. Department of Nursing Science Faculty of Health Sciences Professor Olli Gröhn, Ph.D. A.I. Virtanen Institute for Molecular Sciences Faculty of Health Sciences Professor Kai Kaarniranta, M.D., Ph.D. Institute of Clinical Medicine, Ophthalmology Faculty of Health Sciences Lecturer Veli-Pekka Ranta, Ph.D. (Pharmacy) School of Pharmacy Faculty of Health Sciences Distributor: University of Eastern Finland Kuopio Campus Library P.O.Box 1627 FI-70211 Kuopio, Finland http://www.uef.fi/kirjasto ISBN (print): 978-952-61-1203-9 ISBN (pdf): 978-952-61-1204-6 ISSN (print): 1798-5706 ISSN (pdf): 1798-5714 ISSN-L: 1798-5706 III Author’s address: Department of Neurosurgery Institute of Clinical Medicine School of Medicine, Faculty of Health Sciences University of Eastern Finland KUOPIO FINLAND Supervisors: Professor Juha E Jääskeläinen, M.D., Ph.D. Department of Neurosurgery Institute of Clinical Medicine School of Medicine, Faculty of Health Sciences University of Eastern Finland KUOPIO FINLAND Mikael von und zu Fraunberg, M.D., Ph.D. Department of Neurosurgery Institute of Clinical Medicine School of Medicine, Faculty of Health Sciences University of Eastern Finland KUOPIO FINLAND Reviewers: Associate Professor Martin Lehecka, M.D., Ph.D. Department of Neurosurgery University of Helsinki HELSINKI FINLAND Associate Professor Ville Vuorinen, M.D., Ph.D. Department of Neurosurgery University of Turku TURKU FINLAND Opponent: Professor Tor Ingebrigtsen, M.D., Ph.D. Department of Neurosurgery University of North Norway TROMSO NORWAY IVIV V Lindgren, Antti Elias Eastern Finnish Saccular Intracranial Aneurysm Disease: Role of Type 2 Diabetes and Hypertension, Temporal pattern of incidence. University of Eastern Finland, Faculty of Health Sciences, 2013 Publications of the University of Eastern Finland. Dissertations in Health Sciences. 186. 2013. 85 p. ISBN (print): 978-952-61-1203-9 ISBN (pdf): 978-952-61-1204-6 ISSN (print): 1798-5706 ISSN (pdf): 1798-5714 ISSN-L: 1798-5706 ABSTRACT Saccular intracranial aneurysms (sIAs) form during life at the branching sites of intracranial arteries. Rupture of sIA (sIA-SAH) is the most frequent cause of aneurysmal subarachnoid hemorrhage. The Kuopio sIA Database (www.uef.fi/ns) contains all cases of unruptured sIA(s) and sIA-SAH admitted to Kuopio University Hospital (KUH) since 1980 in Eastern Finland. The purchases of prescribed medicines by sIA patients (1994-2008) were obtained from the national registry. (I) In a cohort of 1862 sIA-SAH patients (1980-2007), Sunday and Monday were the most frequent and Saturday the least frequent weekday on which SAH occurred. We could not identify any etiology to this temporal pattern, and age or gender did not correlate with the Sunday and Monday peaks. (II) In a cohort of 1058 sIA-SAH and 484 unruptured sIA patients (1995-2007), 9% used antidiabetes medication. The incidence of type 2 diabetes did not significantly differ between the groups, suggesting that type 2 diabetes does not increase the risk of sIA-SAH. (III) In a cohort of 1053 sIA-SAH and 467 unruptured sIA patients (1995-2007), 90% of the unruptured sIA patients presented with hypertension, smoking, or familial sIA. Antihypertensive medication was more frequent in the unruptured group (73% vs. 62%), with higher age-adjusted incidence. Untreated hypertension was more frequent in the sIA-SAH group at sIA diagnosis (29% vs. 23%). Size of unruptured sIAs increased with age at sIA diagnosis, independently of hypertension. Our results suggest that drug-treated hypertension is associated with the formation of sIA pouches rather than their rupture. Our study stresses the importance of blood pressure control in carriers of unruptured sIAs. National Library of Medical Classification: Intracranial Aneurysm [C10.228.140.300.510.600] Medical Subject Headings: Intracranial Aneurysm; Subarachnoid Hemorrhage; Type 2 Diabetes Mellitus, Hypertension, Incidence VIVI VII Lindgren, Antti Itäsuomalainen Sakkulaarinen Aivovaltimoaneurysmatauti: Tyypin 2 diabeteksen ja verenpaineen rooli, ilmaantuvuuden vaihtelu. Itä-Suomen yliopisto, Terveystieteiden tiedekunta, 2013 Publications of the University of Eastern Finland. Dissertations in Health Sciences. 186. 2013. 85 s. ISBN (print): 978-952-61-1203-9 ISBN (pdf): 978-952-61-1204-6 ISSN (print): 1798-5706 ISSN (pdf): 1798-5714 ISSN-L: 1798-5706 TIIVISTELMÄ Sakkulaarinen intrakraniaalinen aneurysma (sIA) muodostuu kallonsisäisten, aivojen pinnalla olevien valtimoiden haarautumiskohtiin noin 3%:lla väestöstä. Aneurysmaattinen subaraknoidaalivuoto (aSAV), joka johtuu lähes aina sIA:n puhkeamisesta (sIA-SAV), on aivoverenkiertohäiriön muoto, joka kohdistuu pääasiassa työikäiseen väestöön. Kuopion Aneurysmarekisteri (www.uef.fi/ns) sisältää kaikki aSAV- ja sIA-potilaat, jotka ovat tulleet hoitoon Kuopion yliopistolliseen sairaalaan (KYS) vuodesta 1980 lähtien. Reseptilääkkeiden ostotiedot on yhdistetty aneurysmarekisteriin kansallisesta tietokannasta. (I) Vuosina 1980–2007 1862 sIA-SAV–potilaan kohortissa sunnuntai ja maanantai olivat yleisimmät ja lauantai oli harvinaisin vuotopäivä. Syy esiintyvyyden vaihtelulle ei selvinnyt ja ikä ja sukupuoli eivät vaikuttaneet esiintyvyyshuippuihin. (II) 1058 sIA-SAV potilaasta ja 484 vuotamattomasta sIA-potilaasta (1995–2007) 9 % oli käyttänyt diabeteslääkkeitä. Ryhmien välillä ei ollut merkittävää eroa diabeteksen ikävakioidussa ilmaantuvuudessa, mikä viittaa siihen, että tyypin 2 diabeteksella ei ole vaikutusta sIA-SAV:n esiintyvyyteen. (III) 1053 aSAV-potilaan ja 467 vuotamattoman sIA-potilaan kohortissa (1995–2007) verenpainelääkityksen käyttö oli yleisempää (73 % vs. 62 %), ja verenpaineen ikävakioitu ilmaantuvuus oli suurempi vuotamattomilla. Ainoastaan 10% vuotamattomista potilaista ei käyttänyt verenpainelääkitystä, tupakoinut tai kuulunut aneurysmasukuun. sIA-SAV-potilailla oli enemmän hoitamatonta verenpainetautia ennen aneurysmadiagnoosia (29 % vs. 23 %). Vuotamattoman sIA:n koko lisääntyi iän myötä, verenpaineesta riippumatta. Löydöksemme osoittaa että lääkehoidettu verenpaine liittyy ensisijaisesti sIA:n muodostumiseen. Hoitamaton verenpainetauti voi altistaa aSAV:lle. Tuloksemme korostavat verenpaineen hoidon tärkeyttä anerysmapotilailla. Luokitus: C10.228.140.300.510.600 Yleinen Suomalainen asiasanasto: aneurysma, esiintyvyys, aivot, aivotutkimus, valtimot, aivoverenvuoto, verenpaine, diabetes, aivovaltimoaneurysma VIIIVIII IX To Auni XX XI Acknowledgements This study was carried out in the Department of Neurosurgery, University of Eastern Finland, and in Neurosurgery of NeuroCenter of Kuopio University Hospital, during the years 2010-2013. This thesis was financially supported by University of Eastern Finland, EVO funding of Kuopio University Hospital, Sakari Sohlberg Foundation, North Savo Regional Fund of Finnish Cultural Foundation and Emil Aaltonen Foundation. I am honored to have Tor Ingebrigtsen, M.D., Ph.D., from University of North Norway, Tromso, Norway, as my opponent. I want to thank associate professor Martin Lehecka, M.D., Ph.D., University of Helsinki and associate professor Ville Vuorinen, M.D., Ph.D., University of Turku, for reviewing my thesis. I would like to express my sincere thanks everyone who has contributed to the creation of KUH sIA registry or helped me with this study during these years. In particular, I wish to thank the following: Professor Juha E Jääskeläinen, M.D., Ph.D., my principal supervisor. I owe my deepest gratitude to him for his patient and insightful