Schlaganfall

A. V. Khaw; Ch. Kessler

doi:10.1055/s-0037-1616973

Hämostaseologie, Table of Contents

Hamostaseologie 2006; 26(04): 287-297
DOI: 10.1055/s-0037-1616973

Research Articles

Schattauer GmbH

Schlaganfall

Epidemiologie, Risikofaktoren und GenetikStroke: epidemiology, risk factors, and genetics

A. V. Khaw

¹Klinik und Poliklinik für Neurologie (Direktor: Prof. Dr. C. Kessler) der Ernst-Moritz-Arndt-Universität Greifswald

,

Ch. Kessler

¹Klinik und Poliklinik für Neurologie (Direktor: Prof. Dr. C. Kessler) der Ernst-Moritz-Arndt-Universität Greifswald

› Author Affiliations

Abstract

Zusammenfassung

Der Schlaganfall stellt eine große globale gesundheitspolitische und ökonomische Herausforderung dar. Die Eindämmung des Schlaganfalls kann nur durch genaue Kenntnis der Risikofaktoren und ggf. präventive Intervention erfolgen. Es werden unbeeinflussbare biologische Faktoren (z. B. Geschlecht, Lebensalter, ethnische Herkunft) von proatherosklerotischen bzw. prothrombotischen Risikofaktoren (Hypertonie, Diabetes mellitus, Fettstoffwechselstörungen, serologische und hämostaseologische Faktoren) und kardialer Komorbidität unterschieden. Immer wichtiger werden so genannte Lifestyle-Faktoren (z. B. Rauchen, körperliche Inaktivität und Alkoholkonsum). Neben diesen traditionellen Risikofaktoren hat in den vergangenen Jahren die Beschäftigung mit den genetischen Grundlagen des Schlaganfalls enorm zugenommen. Bei der Suche nach Kandidatengenen werden genetische Varianten (Polymorphismen) funktionell relevanter Gene in Fallkontrollstudien untersucht. Metaanalysen haben eine signifikante Assoziation des Faktor-V-Leiden-Arg506Gln-Polymorphismus, des MTHFR-C677T-Polymorphismus und des ACE-Insertions- Deletions-Polymorphismus zum Schlaganfall gezeigt. Große Hoffnung wird auf populationsbasierte, genomweite Linkage-Analysen gesetzt.

Summary

Stroke constitutes a major global challenge for health policy and healthcare economics. Reducing stroke burden requires extensive knowledge of risk factors and, if applicable, preventive control. Risk factors may be categorized in non-modifiable biological factors, such as age, gender, race/ethnicity; proatherosclerotic/prothrombotic factors (hypertension, diabetes, dyslipidaemia, other serologic and haemostasis factors); cardiac comorbidity (CAD, CHF, atrial fibrillation); lifestyle factors, which play an increasing role, e.g. smoking, physical inactivity, alcohol consumption. These traditional risk factors are extended by rapidly growing efforts in elucidating genetic backgrounds for stroke. Genetic polymorphisms of functionally or pathophysiologically important proteins are investigated in the setting of case-control-studies for their role as candidate genes. Metaanalyses have corroborated the association of the factor V-Leiden arg506gln, MTHFR-C677T, and ACE-insertion- deletion polymorphisms with stroke. Current population- based, genome-wide linkage analyses face high expectations for identifying new genetic risk factors.

Schlüsselwörter

Schlaganfall - Epidemiologie - Risikofaktoren - Genetik

Keywords

Stroke - epidemiology - risk factors - genetics

Full Text

References

Literatur
1 Abbott RD, Donahue RP, MacMahon SW. et al. Diabetes and the risk of stroke: the Honolulu Heart Program. JAMA 1987; 257: 949-52.
2 Abbott RD, Rodriquez BL, Burchfiel CM. et al. Physical activity in older middle-aged men and reduced risk of stroke: the Honolulu Heart Program. Am J Epidemiol 1994; 139: 881-93.
3 Adams Jr HP, Bendixen BH, Kappelle LJ. et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993; 24: 35-41.
4 Anderson CS, Jamrozik KD, Burvill PW. et al. Determining the incidence of different subtypes of stroke: results from the Perth Community Stroke Study, 1989–1990. Med J Aust 1993; 158: 85-9.
5 Ariyo AA, Thach C, Tracy R. Cardiovascular Health Study Investigators.. Lp(a) lipoprotein, vascular disease, and mortality in the elderly. N Engl J Med 2003; 349: 2108-15.
6 Asia Pacific Cohort Studies Collaboration.. Blood pressure and cardiovascular disease in the Asia Pacific region. J Hypertens 2003; 21: 707-16.
7 Austin H, Chimowitz MI, Hill HA. et al. for the Genetics and Stroke in the Young Study Group. Cryptogenic stroke in relation to genetic variation in clotting factors and other genetic polymorphisms among young men and women. Stroke 2002; 33: 2762-8.
8 Bak S, Gaist D, Sindrup SH. et al. Genetic liability in stroke: a long-term follow-up study of Danish twins. Stroke 2002; 33: 769-74.
9 Bamford J, Sandercock P, Dennis M. et al. A prospective study of acute cerebrovascular disease in the community: the Oxfordshire Community Stroke Project 1981–1986, II: incidence, case fatality rates and overall outcome at one year of cerebral infarction, primary intracerebral haemorrhage and subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry 1990; 53: 16-22.
10 Bautista LE, Arenas IA, Penuela A. et al. Total plasma homocysteine level and risk of cardiovascular disease: a meta-analysis of prospective cohort studies. J Clin Epidemiol 2002; 55: 882-7.
11 Berger K, Schulte H, Stögbauer F. et al. Incidence and risk factors for stroke in an occupational cohort: the PROCAM study. Stroke 1998; 29: 1562-6.
12 Bermudez EA, Rifai N, Buring J. et al. Interrelationships among circulating interleukin-6, C-reactive protein, and traditional cardiovascular risk factors in women. Arterioscler Thromb Vasc Biol 2002; 22: 1668-73.
13 Bevan S, Porteous L, Sitzer M. et al. Phosphodiesterase 4D gene, ischemic stroke, and asymptomatic carotid atherosclerosis. Stroke 2005; 36: 949-53.
14 Bikkina M, Levy D, Evans JC. et al. Left ventricular mass and risk of stroke in an elderly cohort. The Framingham Heart Study. JAMA 1994; 272: 33-6.
15 Bots ML, Launer LJ, Lindemans J. et al. Homocysteine and short-term risk of myocardial infarction and stroke in the elderly: the Rotterdam Study. Arch Intern Med 1999; 159: 38-44.
16 Brass LM, Isaacsohn JL, Merikangas KR. et al. A study of twins and stroke. Stroke 1992; 23: 221-3.
17 Broderick J, Brott T, Kothari R. et al. The Greater Cincinnati/Northern Kentucky Stroke Study: preliminary first-ever and total incidence rates of stroke among blacks. Stroke 1998; 29: 415-21.
18 Broderick JP, Phillips SJ, O’Fallon WM. et al. Relationship of cardiac disease to stroke occurrence, recurrence, and mortality. Stroke 1992; 23: 1250-6.
19 Brown RD, Whisnant JP, Sicks JD. et al. Stroke incidence, prevalence, and survival: secular trends in Rochester, Minnesota, through 1989. Stroke 1996; 27: 373-80.
20 Burchfiel CM, Curb JD, Rodriguez BL. et al. Glucose intolerance and 22-year stroke incidence. The Honolulu Heart Program. Stroke 1994; 25: 951-7.
21 Buring JE, Hebert R, Romero J. et al. Migraine and subsequent risk of stroke in the Physicians’ Health Study. Arch Neurol 1995; 52: 129-34.
22 Cambien F, Poirier O, Lecerf L. et al. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 1992; 359: 641-4.
23 Cao JJ, Thach C, Manolio TA. et al. C-reactive protein, carotid intima-media thickness, and incidence of ischemic stroke in the elderly: the Cardiovascular Health Study. Circulation 2003; 108: 166-70.
24 Carlsson LE, Greinacher A, Spitzer C. et al. Polymorphisms of the human platelet antigens HPA-1, HPA-2,HPA-3, and HPA-5 on the platelet receptors for fibrinogen (GPIIb/IIIa), von Willebrand factor (GPIb/IX), and collagen (GPIa/IIa) are not correlated with an increased risk of stroke. Stroke 1997; 28: 1392-5.
25 Carlsson LE, Santoso S, Spitzer C. et al. The alpha2 gene coding sequence T807/A873 of the platelet collagen receptor integrin A2/B1 is a genetic risk factor for the development of stroke in younger patients. Blood 1999; 93: 3583-6.
26 Carolei A, Marini C, Di Napoli M. et al. High stroke incidence in the prospective community-based L’Aquila registry (1994–1998): first year’s results. Stroke 1997; 28: 2500-6.
27 Casas JP, Hingorani A, Bautista LE. et al. Metaanalysis of genetic studies in ischemic stroke. Arch Neurol 2004; 61: 1652-61.
28 Chambless LE, Folsom AR, Clegg LX. et al. Carotid wall thickness is predictive of incident clinical stroke: the Atherosclerosis Risk in Communities (ARIC) study. Am J Epidemiol 2000; 151: 478-87.
29 Chan AK, deVeber G. Prothrombotic disorders and ischemic stroke in children. Sem Pediatr Neurol 2000; 7: 301-8.
30 Chang CL, Donaghy M, Poulter N. Migraine and stroke in young women: case-control study. The World Health Organisation Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Br Med J 1999; 318 7175 13-8.
31 Chasan-Taber L, Stampfer MJ. Epidemiology of oral contraceptives and cardiovascular disease. Ann Intern Med 1998; 128: 467-77.
32 Curb JD, Abbott RD, Rodriguez BL. et al. C-reactive protein and the future risk of thromboembolic stroke in healthy men. Circulation 2003; 107: 2016-20.
33 D´Agostino RB, Wolf PA, Belanger AJ. et al. Stroke risk profile: adjustment for antihypertensive medication. The Framingham Study. Stroke 1994; 25: 40-3.
34 D’Alessandro G, Di Giovanni M, Roveyaz L. et al. Incidence and prognosis of stroke in the Valle d‘Aosta, Italy: first-year results of a communitybased study. Stroke 1992; 23: 1712-5.
35 Danesh J, Lewington S, Thompson SG. et al. for the Fibrinogen Studies Collaboration. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA 2005; 294: 1799-809.
36 Davis PH, Dambrosia JM, Schoenberg BS. et al. Risk factors for ischemic stroke: a prospective study in Rochester, Minnesota. Ann Neurol 1987; 22: 319-27.
37 De Groot JC, de Leeuw FE, Oudkerk M. et al. Cerebral white matter lesions and cognitive function: the Rotterdam Scan Study. Ann Neurol 2000; 47: 145-51.
38 De Leeuw FE, de Groot JC, Oudkerk M. et al. Hypertension and cerebral white matter lesions in a prospective cohort study. Brain 2002; 125: 765-72.
39 Demarmels Biasiutti F, Berger D, Mattle HP. et al. Hemostatic risk factors in ischemic stroke. Thromb Haemost 2003; 90: 1094-9.
40 Devuyst G, Bogousslavsky J. Patent foramen ovale: the never-ending story. Curr Treat Options Cardiovasc Med 2005; 7: 227-39.
41 Djousse L, Ellison RC, Beiser A. et al. Alcohol consumption and risk of ischemic stroke. The Framingham Study. Stroke 2002; 33: 907-12.
42 Donahue RP, Abbott RD, Reed DM. et al. Alcohol and hemorrhagic stroke: the Honolulu Heart Program. JAMA 1986; 255: 2311-4.
43 Elkind MS, Sciacca R, Boden-Albala B. et al. Moderate alcohol consumption reduces risk of ischemic stroke: the Northern Manhattan Study. Stroke 2006; 37: 13-9.
44 Ellekjaer H, Holmen J, Indredavik B. et al. Epidemiology of stroke in Innherred, Norway, 1994 to 1996: incidence and 30-day case-fatality rate. Stroke 1997; 28: 2180-4.
45 Feigin VL, Wiebers DO, Nikitin YP. et al. Risk factors for ischemic stroke in a Russian community: a population-based case-control study. Stroke 1998; 29: 34-9.
46 Ford ES, Giles WH. Serum C-reactive protein and self-reported stroke: findings from the Third National Health and Nutrition Examination Survey. Arterioscler Thromb Vasc Biol 2000; 20: 1052-6.
47 Foulkes MA, Wolf PA, Price TR. et al. The Stroke Data Bank: Design, methods, and baseline characteristics. Stroke 1988; 19: 547-54.
48 Fox CS, Cupples LA, Chazaro I. et al. Genomewide linkage analysis for internal carotid artery intimal medial thickness: evidence for linkage to chromosome 12. Am J Hum Genet 2004; 74: 253-61.
49 Gillum RF, Mussolino ME, Ingram DD. Physical activity and stroke incidence in women and men: the NHANES I epidemiologic follow-up study. Am J Epidemiol 1996; 143: 860-9.
50 Giroud M, Milan C, Beuriat P. et al. Incidence and survival rates during a two-year period of intracerebral and subarachnoid haemorrhages, cortical infarcts, lacunes and transient ischaemic attacks: the stroke registry of Dijon: 1985–1989. Int J Epidemiol 1991; 20: 892-9.
51 Gretarsdottir S, Sveinbjornsdottir S, Jonsson HH. et al. Localization of a susceptibility gene for common forms of stroke to 5q12. Am J Hum Genet 2002; 70: 593-603.
52 Gretarsdottir S, Thorleifsson G, Reynisdottir ST. et al. The gene encoding phosphodiesterase 4D confers risk of ischemic stroke. Nat Genet 2003; 35: 131-8.
53 Hankey GJ, Eikelboom JW, van Bockxmeer FM. et al. Inherited thrombophilia in ischemic stroke and its pathogenic subtypes. Stroke 2001; 32: 1793-9.
54 Hassan A, Hunt BJ, O’Sullivan M. et al. Markers of endothelial dysfunction in lacunar infarction and ischemic leukoaraiosis. Brain 2003; 126: 424-32.
55 Hassan A, Markus HS. Genetics in ischemic stroke. Brain 2000; 133: 1784-812.
56 Heinemann LA, Lewis MA, Thorogood M. et al. Case-control study of oral contraceptives and risk of thromboembolic stroke: results from International Study on Oral Contraceptives and Health of Young Women. Br Med J 1997; 315 7121 1502-4.
57 Henkens LHG, Kroon AA, van Boxte MPJ. et al. Associations of the angiotensin II type 1 receptor A1166C and the endothelial NO synthase G894T gene polymorphisms with silent subcortical white matter lesions in essential hypertension. Stroke 2005; 36: 1869-73.
58 Heywood DM, Carter AM, Catto AJ. et al. Polymorphisms of the factor VII gene and circulating FVII:C levels in relation to acute cerebrovascular disease and poststroke mortality. Stroke 1997; 28: 816-21.
59 Homma S, Sacco RL, Di Tullio MR. et al.; PFO in Cryptogenic Stroke Study (PICSS) Investigators.. Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in Cryptogenic Stroke Study. Circulation 2002; 105: 2625-31.
60 Homocysteine Studies Collaboration.. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 2002; 288: 2015-22.
61 Hu FB, Stampfer MJ, Colditz GA. et al. Physical activity and risk of stroke in women. JAMA 2000; 283: 2961-7.
62 Hu G, Tuomilehto J, Silventoinen K. et al. Joint effects of physical activity, body mass index, waist circumference and waist-to-hip ratio with the risk of cardiovascular disease among middle-aged Finnish men and women. Eur Heart J 2004; 25: 2212-9.
63 Hulley S, Grady D, Bush T. et al.; the HERS Research Group.. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998; 280: 605-11.
64 Iso H, Baba S, Mannami T. et al; JPHC Study Group.. Alcohol consumption and risk of stroke among middle-aged men: the JPHC Study Cohort I. Stroke 2004; 35: 1124-9.
65 Jeng JS, Sacco RL, Kargman DE. et al. Apolipoproteins and carotid artery atherosclerosis in an elderly multiethnic population: the Northern Manhattan stroke study. Atherosclerosis 2002; 165: 317-25.
66 Jerrard-Dunne P, Cloud G, Hassan A. et al. Evaluating the genetic component of ischemic stroke subtypes: a family history study. Stroke 2003; 34: 1364-9.
67 Johansson L, Jansson JH, Boman K. et al. Tissue plasminogen activator, plasminogen activator inhibitor- 1, and tissue plasminogen activator/plasminogen activator inhibitor-1 complex as risk factors for the development of a first stroke. Stroke 2000; 31: 26-32.
68 Jorgensen H, Nakayama H, Raaschou HO. et al. Stroke in patients with diabetes: the Copenhagen Stroke Study. Stroke 1994; 25: 1977-84.
69 Jorgensen HS, Plesner AM, Hubbe P. et al. Marked increase of stroke incidence in men between 1972 and 1990 in Frederiksberg, Denmark. Stroke 1992; 23: 1701-4.
70 Jousilahti P, Rastenyte D, Tuomilehto J. et al. Parental history of cardiovascular disease and risk of stroke: a prospective follow-up of 14 371 middleaged men and women in Finland. Stroke 1997; 28: 1361-6.
71 Kannel WB, Cupples LA, Ramaswami R. et al. Regional obesity and risk of cardiovascular disease; the Framingham Study. J Clin Epidemiol 1991; 44: 183-90.
72 Kannel WB, Wolf PA, Castelli WP. et al. Fibrinogen and risk of cardiovascular disease. The Framingham Study. JAMA 1987; 258: 1183-6.
73 Kawachi I, Colditz GA, Stampfer MJ. et al. Smoking cessation and decreased risk of stroke in women. JAMA 1993; 269: 232-6.
74 Kay R, Woo J, Kreel L. et al. Stroke subtypes among Chinese living in Hong Kong: the Shatin Stroke Registry. Neurology 1992; 42: 985-7.
75 Kelly-Hayes M, Wolf PA, Kase CS. et al. Temporal patterns of stroke onset. The Framingham Study. Stroke 1995; 26: 1343-7.
76 Kelly PJ, Rosand J, Kistler JP. et al. Homocysteine, MTHFR 677C→T polymorphism, and risk of ischemic stroke: results of a meta-analysis. Neurology 2002; 59: 529-36.
77 Khaw KT, Barrett-Connor E. Family history of stroke as an independent predictor of ischemic heart disease in men and stroke in women. Am J Epidemiol 1986; 123: 59-66.
78 Kiely DK, Wolf PA, Cupples LA. et al. Physical activity and stroke risk: the Framingham Study. Am J Epidemiol 1994; 140: 608-20.
79 Kiely DK, Wolf PA, Cupples LA. et al. Familial aggregation of stroke. The Framingham Study. Stroke 1993; 24: 1366-71.
80 Kim RJ, Becker RC. Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: a metaanalysis of published studies. Am Heart J 2003; 146: 948-57.
81 Kimura Y, Takishita S, Muratani H. et al. Demographic study of first-ever stroke and acute myocardial infarction in Okinawa, Japan. Intern Med 1998; 37: 736-45.
82 Kolominsky-Rabas PL, Sarti C, Heuschmann PU. et al. A prospective community-based study of stroke in Germany, the Erlangen Stroke Project (ESPro): incidence and case fatality at 1, 3, and 12 months. Stroke 1998; 29: 2501-6.
83 Kristensen B, Malm J, Nilsson TK. et al. Increased fibrinogen levels and acquired hypofibrinolysis in young adults with ischemic stroke. Stroke 1998; 29: 2261-7.
84 Kuhlenbäumer G, Berger K, Huge A. et al. Evaluation of single nucleotide polymorphisms in the phosphodiesterase 4D gene (PDE4D) and their assoziation with ischemic stroke in a large german cohort. J Neurol Neurosurg Psychiatry 2006; 77: 521-4.
85 Kurth T, Kase CS, Berger K. et al. Smoking and the risk of hemorrhagic stroke in men. Stroke 2003; 34: 1151-5.
86 Lalouschek W, Schillinger M, Hsieh K. et al. Matched case-control study on factor V Leiden and the prothrombin G20210A mutation in patients with ischemic stroke/transient ischemic attack up to the age of 60 years. Stroke 2005; 36: 1405-9.
87 Lamy C, Giannesini C, Zuber M. et al. Clinical and imaging findings in cryptogenic stroke patients with and without patent foramen ovale: the PFOASA Study. Atrial Septal Aneurysm. Stroke 2002; 33: 706-11.
88 Larsson B, Svardsudd K, Welin L. et al. Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: 13 year follow up of participants in the study of men born in 1913. Br Med J (Clin Res Ed) 1984; 288 6428 1401-4.
89 Lauria G, Gentile M, Fassetta G. et al. Incidence and prognosis of stroke in the Belluno province, Italy: first-year results of a community-based study. Stroke 1995; 26: 1787-93.
90 Lindenstrøm E, Boysen G, Nyboe J. Lifestyle factors and risk of cerebrovascular disease in women: the Copenhagen City Heart Study. Stroke 1993; 24: 1468-72.
91 Lohmussaar E, Gschwendtner A, Mueller JC. et al. ALOX5AP gene and the PDE4D gene in a central European population of stroke patients. Stroke. 2005; 36: 731-6.
92 Lynch JK, Han CJ, Nee LE. et al. Prothrombotic factors in children with stroke or porencephaly. Pediatrics 2005; 116: 447-53.
93 Lynch JK, Nelson KB. Epidemiology of perinatal stroke. Curr Opin Pediatr 2001; 13: 499-505.
94 Macko RF, Kittner SJ, Epstein A. et al. Elevated tissue plasminogen activator antigen and stroke risk: The Stroke Prevention In Young Women Study. Stroke 1999; 30: 7-11.
95 Mannami T, Iso H, Baba S. et al; Japan Public Health Center-Based Prospective Study on Cancer and Cardiovascular Disease Group.. Cigarette smoking and risk of stroke and its subtypes among middle-aged Japanese men and women: the JPHC Study Cohort I. Stroke 2004; 35: 1248-53.
96 Mas JL, Zuber M. Recurrent cerebrovascular events in patients with patent foramen ovale, atrial septal aneurysm, or both and cryptogenic stroke or transient ischemic attack. French Study Group on Patent Foramen Ovale and Atrial Septal Aneurysm. Am Heart J 1995; 130: 1083-8.
97 McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969; 56: 111-28.
98 Meissner I, Khandheria BK, Heit JA. et al. Patent foramen ovale: innocent or guilty? Evidence from a prospective population-based study. J Am Coll Cardiol 2006; 47: 440-5.
99 Mercuri E, Cowan F, Gupte G. et al. Prothrombotic disorders and abnormal neurodevelopmental outcome in infants with neonatal cerebral infarction. Pediatrics 2001; 107: 1400-4.
100 Merikangas KR, Fenton BT, Cheng SH. et al. Association between migraine and stroke in a largescale epidemiological study of the United States. Arch Neurol 1997; 54: 362-8.
101 Mukamal KJ, Ascherio A, Mittleman MA. et al. Alcohol and risk for ischemic stroke in men: The role of drinking patterns and usual beverage. Ann Intern Med 2005; 142: 11-9.
102 Mukamal KJ, Chung H, Jenny NS. et al. Alcohol use and risk of ischemic stroke among older adults: the cardiovascular health study. Stroke 2005; 36: 1830-4.
103 Ninomiya JK, L’Italien G, Criqui MH. et al. Association of the metabolic syndrome with history of myocardial infarction and stroke in the Third National Health and Nutrition Examination Survey. Circulation 2004; 109: 42-6.
104 Numminen H, Kotila M, Waltimo O. et al. Declining incidence and mortality rates of stroke in Finland from 1972 to 1991: results of three population- based stroke registers. Stroke 1996; 27: 1487-91.
105 Petitti DB, Sidney S, Bernstein A. et al. Stroke in users of low-dose oral contraceptives. N Engl J Med 1996; 335: 8-15.
106 Pradhan AD, Manson JE, Rossouw JE. et al. Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: prospective analysis from the Women’s Health Initiative observational study. JAMA 2002; 288: 980-7.
107 Prospective Studies Collaboration.. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360: 1903-13.
108 Prospective Studies Collaboration.. Cholesterol, diastolic blood pressure, and stroke: 13,000 strokes in 450,000 people in 45 prospective cohorts. Lancet 1995; 346 8991–8992 1647-53.
109 Qureshi AI, Suri MF, Mohammad Y. et al. Isolated and borderline isolated systolic hypertension relative to long-term risk and type of stroke: a 20-year follow-up of the national health and nutrition survey. Stroke 2002; 33: 2781-8.
110 Rexrode KM, Hennekens CH, Willett WC. et al. A prospective study of body mass index, weight change, and risk of stroke in women. JAMA 1997; 277: 1539-45.
111 Ricci S, Celani MG, La Rosa F. et al. SEPIVAC: a community-based study of stroke incidence in Umbria, Italy. J Neurol Neurosurg Psychiatry. 1991; 54: 695-8.
112 Ridker PM, Buring JE, Shih J. et al. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation 1998; 98: 731-3.
113 Ridker PM, Hennekens CH, Buring JE. et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000; 342: 836-43.
114 Ridker PM, Rifai N, Rose L. et al. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 2002; 347: 1557-65.
115 Rosamond WD, Folsom AR, Chambless LE. et al. Stroke incidence and survival among middleaged adults: 9-year follow-up of the Atherosclerosis Risk in Communities (ARIC) cohort. Stroke 1999; 30: 736-43.
116 Rost NS, Wolf PA, Kase CS. et al. Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham study. Stroke 2001; 32: 2575-9.
117 Rothwell PM, Coull AJ, Giles MF. et al. Change in stroke incidence, mortality, case-fatality, severity, and risk factors in Oxfordshire, UK from 1981 to 2004 (Oxford Vascular Study). Lancet 2004; 363: 1925-33.
118 Rothwell PM. Prevention of stroke in patients with diabetes mellitus and the metabolic syndrome. Cerebrovasc Dis 2005; 20 (Suppl. 01) 24-34.
119 Sacco RL, Anand K, Lee HS. et al. Homocysteine and the risk of ischemic stroke in a triethnic cohort: the Northern Manhattan Study. Stroke 2004; 35: 2263-9.
120 Sacco RL, Benson RT, Kargman DE. et al. Highdensity lipoprotein cholesterol and ischemic stroke in the elderly: the Northern Manhattan Stroke Study. JAMA 2001; 285: 2729-35.
121 Sacco RL, Boden-Albala B, Gan R. et al. Stroke incidence among white, black, and Hispanic residents of an urban community: the Northern Manhattan Stroke Study. Am J Epidemiol 1998; 147: 259-68.
122 Sacco RL, Gan R, Boden-Albala B. et al. Leisuretime physical activity and ischemic stroke risk: the Northern Manhattan Stroke Study. Stroke 1998; 29: 380-7.
123 Sarti C, Stegmayr B, Tolonen H. et al. Are changes in mortality from stroke caused by changes in stroke event rates or case fatality? Results from the WHO MONICA Project. Stroke 2003; 34: 1833-40.
124 Sarti C, Rastenyte D, Cepaitis Z. et al. International trends in mortality from stroke, 1968 to 1994. Stroke 2000; 31: 1588-601.
125 Seshadri S, Beiser A, Kelly-Hayes M. et al. The lifetime risk of stroke: estimates from the Framingham Study. Stroke 2006; 37: 345-50.
126 Shahar E, Chambless LE, Rosamond WD. et al. Plasma lipid profile and incident ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) study. Stroke 2003; 34: 623-31.
127 Sharma P. Meta-analysis of the ACE gene in ischaemic stroke. J Neurol Neurosurg Psychiatry 1998; 64: 227-30.
128 Simon JA, Hsia J, Cauley JA. et al. the HERS Research Group. Postmenopausal hormone therapy and risk of stroke: the Heart and Estrogen-progestin Replacement Study (HERS). Circulation 2001; 103: 638-42.
129 Singhal S, Bevan S, Barrick T. et al. The influence of genetic and cardiovascular risk factors on the CADASIL phenotype. Brain 2004; 127: 2031-8.
130 Smiles AM, Jenny NS, Tang Z. et al. No association of plasma prothrombin concentration or the G20210A mutation with incident cardiovascular disease: results from the Cardiovascular Health Study. Thromb Haemost 2002; 87: 614-21.
131 Smith FB, Lee AJ, Fowkes FG. et al. Hemostatic factors as predictors of ischemic heart disease and stroke in the Edinburgh Artery Study. Arterioscler Thromb Vasc Biol 1997; 17: 3321-5.
132 Stampfer MJ, Colditz GA, Willett WC. et al. Postmenopausal estrogen therapy and cardiovascular disease. Ten-year follow-up from the nurses’ health study. N Engl J Med 1991; 325: 756-62.
133 Stewart JA, Dundas R, Howard RS. et al. Ethnic differences in incidence of stroke: prospective study with stroke register. Br Med J 1999; 318: 967-71.
134 Strandberg TE, Tilvis RS. C-reactive protein, cardiovascular risk factors, and mortality in a prospective study in the elderly. Arterioscler Thromb Vasc Biol 2000; 20: 1057-60.
135 Sudlow CL, Warlow CP. Comparable studies of the incidence of stroke and its pathological types: results from an international collaboration. International Stroke Incidence Collaboration. Stroke 1997; 28: 491-9.
136 Suk SH, Sacco RL, Boden-Albala B. et al. Northern Manhattan Stroke Study. Abdominal obesity and risk of ischemic stroke: the Northern Manhattan Stroke Study. Stroke 2003; 34: 1586-92.
137 Thom T, Haase N, Rosamond W. et al. Heart Disease and Stroke Statistics – 2006 Update. A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2006; 113: e85.
138 Thomas CE. Patent foramen ovale and stroke risk: incidental finding or causal culprit?. Sem Neurol 2005; 25: 371-5.
139 Thorand B, Lowel H, Schneider A. et al. C-reactive protein as a predictor for incident diabetes mellitus among middle-aged men: results from the MONICA Augsburg cohort study, 1984–1998. Arch Intern Med 2003; 163: 93-9.
140 Thorvaldsen P, Kuulasmaa K, Rajakangas AM. et al. Stroke trends in the WHO MONICA Project. Stroke 1997; 28: 500-6.
141 Tournier-Lasserve E, Iba-Zizen MT, Romero N. et al. Autosomal dominant syndrome with strokelike episodes and leukoencephalopathy. Stroke 1991; 22: 1297-302.
142 Tzourio C, Tehindrazanarivelo A, Iglesias S. et al. Case-control study of migraine and risk of ischaemic stroke in young women. Br Med J 1995; 310: 830-3.
143 Van Exel E, Gussekloo J, de Craen AJ. et al. Inflammation and stroke: the Leiden 85-Plus Study. Stroke 2002; 33: 1135-8.
144 Vemmos KN, Bots ML, Tsibouris PK. et al. Stroke incidence and case fatality in southern Greece: the Arcadia stroke registry. Stroke 1999; 30: 363-70.
145 Wendel-Vos GC, Schuit AJ, Feskens EJ. et al. Physical activity and stroke. A meta-analysis of observational data. Int J Epidemiol 2004; 33: 787-98.
146 WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception.. Haemorrhagic stroke, overall stroke risk, and combined oral contraceptives: results of an international, multicentre, case-control study. Lancet 1996; 348 9026 505-10.
147 Wiesner G, Grimm J. Bittner. Schlaganfall: Prävalenz, Inzidenz, Trend, Ost-West-Vergleich. Erste Ergebnisse aus dem Bundes-Gesundheitssurvey 1998. Gesundheitswesen 1999; 61 (Suppl. 02) S79-84.
148 Wilhelmsen L, Svardsudd K, Korsan-Bengtsen K. et al. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med 1984; 311: 501-5.
149 Williams RR, Hunt SC, Heiss G. et al. Usefulness of cardiovascular family history data for population- based preventive medicine and medical research (the Health Family Tree Study and the NHLBI Family Heart Study). Am J Cardiol 2001; 87: 129-35.
150 Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991; 22: 983-8.
151 Wolf PA, D’Agostino RB, Belanger AJ. et al. Probability of stroke: a risk profile from the Framingham Study. Stroke 1991; 22: 312-8.
152 Woodward M, Lam TH, Barzi F. et al. Asia Pacific Cohort Studies Collaboration. Smoking, quitting, and the risk of cardiovascular disease among women and men in the Asia-Pacific region. Int J Epidemiol 2005; 34: 1036-45.
15 World Health Organization. The atlas of heart disease and stroke. www.who.int/cardiovascular_diseases/en/cvd_atlas_15_burden_stroke. Letzter Zugriff 6. April 2006.
154 World Health Organization. The atlas of heart disease and stroke. www.who.int/cardiovascular_diseases/en/cvd_atlas_01_types. Letzter Zugriff 6. April 2006.
155 World Health Organization. The atlas of heart disease and stroke. www.who.int/cardiovascular_diseases/en/cvd_atlas_16_death_from_stroke. Letzter Zugriff 6. April 2006.
156 Writing Group for the Women’s Health Initiative Investigators.. Risk and benefits of estrogen plus progestin in health postmenopausal women. JAMA 2002; 288: 321-33.
157 Yaggi H, Mohsenin V. Obstructive sleep apnoea and stroke. Lancet Neurol 2004; 3: 333-42.
158 Yano K, Reed DM, MacLean CJ. Serum cholesterol and hemorrhagic stroke in the Honolulu Heart Program. Stroke 1989; 20: 1460-5.
159 Zhang LF, Yang J, Hong Z. et al. Collaborative Group of China Multicenter Study of Cardiovascular Epidemiology. Proportion of different subtypes of stroke in China. Stroke 2003; 34: 2091-6.
160 Zhang X, Patel A, Horibe H. et al. Asia Pacific Cohort Studies Collaboration. Cholesterol, coronary heart disease, and stroke in the Asia Pacific region. Int J Epidemiol 2003; 32: 563-72.