Aneurysmal subarachnoid hemorrhage: Epidemiology, risk factors, and pathogenesis
- Robert J Singer, MD
Robert J Singer, MD
- Associate Professor of Neurosurgery
- Neurovascular Therapeutics
- Geisel School of Medicine at Dartmouth
- Christopher S Ogilvy, MD
Christopher S Ogilvy, MD
- Professor of Surgery
- Harvard Medical School
- Guy Rordorf, MD
Guy Rordorf, MD
- Associate Professor of Neurology
- Harvard Medical School
Twenty percent of strokes are hemorrhagic, with subarachnoid hemorrhage (SAH) and intracerebral hemorrhage, each accounting for 10 percent. Most SAHs are caused by ruptured saccular aneurysms. Other causes include trauma, arteriovenous malformations/fistulae, vasculitides, intracranial arterial dissections, amyloid angiopathy, bleeding diatheses, and illicit drug use (especially cocaine and amphetamines).
The epidemiology and risk factors of aneurysmal SAH are reviewed here. The epidemiology and management of unruptured aneurysms and the clinical features, diagnosis and treatment of aneurysmal SAH, are discussed separately. Mycotic aneurysms and nonaneurysmal subarachnoid hemorrhage are also discussed separately. (See "Unruptured intracranial aneurysms" and "Clinical manifestations and diagnosis of aneurysmal subarachnoid hemorrhage" and "Treatment of aneurysmal subarachnoid hemorrhage" and "Overview of infected (mycotic) arterial aneurysm" and "Nonaneurysmal subarachnoid hemorrhage" and "Perimesencephalic nonaneurysmal subarachnoid hemorrhage".)
The incidence of aneurysmal SAH varies by geographic region. In the United States, the incidence is reportedly between 10 and 15 people per 100,000 population [1,2]. Much lower rates are reported in China (2 cases per 100,000) and in South and Central America (4 per 100,000), while higher rates are reported in Finland and Japan (19 to 23 per 100,000) [3,4].
The mean age at aneurysmal rupture is 55 years . While most aneurysmal SAH occur between 40 and 60 years of age; however young children and the elderly can be affected [6,7]. African Americans appear to be at higher risk than Caucasian Americans . There is a slightly higher incidence of aneurysmal SAH in women, which may relate to hormonal status (see 'Estrogen deficiency' below) [6,9].
Most SAHs are due to the rupture of intracranial aneurysms. Because of this, risk factors for aneurysm formation overlap with risk factors for SAH. Risk factors that are primarily associated with formation of intracranial aneurysms are discussed separately. (See "Unruptured intracranial aneurysms".)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Labovitz DL, Halim AX, Brent B, et al. Subarachnoid hemorrhage incidence among Whites, Blacks and Caribbean Hispanics: the Northern Manhattan Study. Neuroepidemiology 2006; 26:147.
- Shea AM, Reed SD, Curtis LH, et al. Characteristics of nontraumatic subarachnoid hemorrhage in the United States in 2003. Neurosurgery 2007; 61:1131.
- Ingall T, Asplund K, Mähönen M, Bonita R. A multinational comparison of subarachnoid hemorrhage epidemiology in the WHO MONICA stroke study. Stroke 2000; 31:1054.
- de Rooij NK, Linn FH, van der Plas JA, et al. Incidence of subarachnoid haemorrhage: a systematic review with emphasis on region, age, gender and time trends. J Neurol Neurosurg Psychiatry 2007; 78:1365.
- Mayberg MR, Batjer HH, Dacey R, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage. A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 1994; 25:2315.
- Rinkel GJ, Djibuti M, Algra A, van Gijn J. Prevalence and risk of rupture of intracranial aneurysms: a systematic review. Stroke 1998; 29:251.
- Jordan LC, Johnston SC, Wu YW, et al. The importance of cerebral aneurysms in childhood hemorrhagic stroke: a population-based study. Stroke 2009; 40:400.
- Broderick JP, Brott T, Tomsick T, et al. The risk of subarachnoid and intracerebral hemorrhages in blacks as compared with whites. N Engl J Med 1992; 326:733.
- Sarti C, Tuomilehto J, Salomaa V, et al. Epidemiology of subarachnoid hemorrhage in Finland from 1983 to 1985. Stroke 1991; 22:848.
- Vlak MH, Rinkel GJ, Greebe P, et al. Lifetime risks for aneurysmal subarachnoid haemorrhage: multivariable risk stratification. J Neurol Neurosurg Psychiatry 2013; 84:619.
- Knekt P, Reunanen A, Aho K, et al. Risk factors for subarachnoid hemorrhage in a longitudinal population study. J Clin Epidemiol 1991; 44:933.
- Anderson CS, Feigin V, Bennett D, et al. Active and passive smoking and the risk of subarachnoid hemorrhage: an international population-based case-control study. Stroke 2004; 35:633.
- Feigin VL, Rinkel GJ, Lawes CM, et al. Risk factors for subarachnoid hemorrhage: an updated systematic review of epidemiological studies. Stroke 2005; 36:2773.
- Feigin V, Parag V, Lawes CM, et al. Smoking and elevated blood pressure are the most important risk factors for subarachnoid hemorrhage in the Asia-Pacific region: an overview of 26 cohorts involving 306,620 participants. Stroke 2005; 36:1360.
- Sandvei MS, Romundstad PR, Müller TB, et al. Risk factors for aneurysmal subarachnoid hemorrhage in a prospective population study: the HUNT study in Norway. Stroke 2009; 40:1958.
- Kim CK, Kim BJ, Ryu WS, et al. Impact of smoking cessation on the risk of subarachnoid haemorrhage: a nationwide multicentre case control study. J Neurol Neurosurg Psychiatry 2012; 83:1100.
- Lindekleiv H, Sandvei MS, Romundstad PR, et al. Joint effect of modifiable risk factors on the risk of aneurysmal subarachnoid hemorrhage: a cohort study. Stroke 2012; 43:1885.
- Lindekleiv H, Sandvei MS, Njølstad I, et al. Sex differences in risk factors for aneurysmal subarachnoid hemorrhage: a cohort study. Neurology 2011; 76:637.
- Woo D, Haverbusch M, Sekar P, et al. Effect of untreated hypertension on hemorrhagic stroke. Stroke 2004; 35:1703.
- Inagawa T. Risk factors for aneurysmal subarachnoid hemorrhage in patients in Izumo City, Japan. J Neurosurg 2005; 102:60.
- Korja M, Silventoinen K, McCarron P, et al. Genetic epidemiology of spontaneous subarachnoid hemorrhage: Nordic Twin Study. Stroke 2010; 41:2458.
- Okamoto K, Horisawa R, Kawamura T, et al. Family history and risk of subarachnoid hemorrhage: a case-control study in Nagoya, Japan. Stroke 2003; 34:422.
- van der Jagt M, Hasan D, Bijvoet HW, et al. Validity of prediction of the site of ruptured intracranial aneurysms with CT. Neurology 1999; 52:34.
- Broderick JP, Brown RD Jr, Sauerbeck L, et al. Greater rupture risk for familial as compared to sporadic unruptured intracranial aneurysms. Stroke 2009; 40:1952.
- Onda H, Kasuya H, Yoneyama T, et al. Genomewide-linkage and haplotype-association studies map intracranial aneurysm to chromosome 7q11. Am J Hum Genet 2001; 69:804.
- Farnham JM, Camp NJ, Neuhausen SL, et al. Confirmation of chromosome 7q11 locus for predisposition to intracranial aneurysm. Hum Genet 2004; 114:250.
- Ruigrok YM, Seitz U, Wolterink S, et al. Association of polymorphisms and haplotypes in the elastin gene in Dutch patients with sporadic aneurysmal subarachnoid hemorrhage. Stroke 2004; 35:2064.
- Nahed BV, Seker A, Guclu B, et al. Mapping a Mendelian form of intracranial aneurysm to 1p34.3-p36.13. Am J Hum Genet 2005; 76:172.
- Roos YB, Pals G, Struycken PM, et al. Genome-wide linkage in a large Dutch consanguineous family maps a locus for intracranial aneurysms to chromosome 2p13. Stroke 2004; 35:2276.
- Olsson S, Csajbok LZ, Jood K, et al. Association between genetic variation on chromosome 9p21 and aneurysmal subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry 2011; 82:384.
- Ozturk AK, Nahed BV, Bydon M, et al. Molecular genetic analysis of two large kindreds with intracranial aneurysms demonstrates linkage to 11q24-25 and 14q23-31. Stroke 2006; 37:1021.
- Olson JM, Vongpunsawad S, Kuivaniemi H, et al. Search for intracranial aneurysm susceptibility gene(s) using Finnish families. BMC Med Genet 2002; 3:7.
- van der Voet M, Olson JM, Kuivaniemi H, et al. Intracranial aneurysms in Finnish families: confirmation of linkage and refinement of the interval to chromosome 19q13.3. Am J Hum Genet 2004; 74:564.
- Yamada S, Utsunomiya M, Inoue K, et al. Genome-wide scan for Japanese familial intracranial aneurysms: linkage to several chromosomal regions. Circulation 2004; 110:3727.
- Iniesta JA, González-Conejero R, Piqueras C, et al. Platelet GP IIIa polymorphism HPA-1 (PlA) protects against subarachnoid hemorrhage. Stroke 2004; 35:2282.
- Foroud T, Koller DL, Lai D, et al. Genome-wide association study of intracranial aneurysms confirms role of Anril and SOX17 in disease risk. Stroke 2012; 43:2846.
- Schievink WI, Schaid DJ, Rogers HM, et al. On the inheritance of intracranial aneurysms. Stroke 1994; 25:2028.
- Bromberg JE, Rinkel GJ, Algra A, et al. Familial subarachnoid hemorrhage: distinctive features and patterns of inheritance. Ann Neurol 1995; 38:929.
- Ruigrok YM, Rinkel GJ, Wijmenga C, Van Gijn J. Anticipation and phenotype in familial intracranial aneurysms. J Neurol Neurosurg Psychiatry 2004; 75:1436.
- Leppälä JM, Paunio M, Virtamo J, et al. Alcohol consumption and stroke incidence in male smokers. Circulation 1999; 100:1209.
- Kernan WN, Viscoli CM, Brass LM, et al. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med 2000; 343:1826.
- Yoon BW, Bae HJ, Hong KS, et al. Phenylpropanolamine contained in cold remedies and risk of hemorrhagic stroke. Neurology 2007; 68:146.
- Lee SM, Choi NK, Lee BC, et al. Caffeine-containing medicines increase the risk of hemorrhagic stroke. Stroke 2013; 44:2139.
- Levine SR, Brust JC, Futrell N, et al. A comparative study of the cerebrovascular complications of cocaine: alkaloidal versus hydrochloride--a review. Neurology 1991; 41:1173.
- Nolte KB, Brass LM, Fletterick CF. Intracranial hemorrhage associated with cocaine abuse: a prospective autopsy study. Neurology 1996; 46:1291.
- Bederson JB, Connolly ES Jr, Batjer HH, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 2009; 40:994.
- Ago M, Ago K, Hara K, et al. Toxicological and histopathological analysis of a patient who died nine days after a single intravenous dose of methamphetamine: a case report. Leg Med (Tokyo) 2006; 8:235.
- Ho EL, Josephson SA, Lee HS, Smith WS. Cerebrovascular complications of methamphetamine abuse. Neurocrit Care 2009; 10:295.
- Beadell NC, Thompson EM, Delashaw JB, Cetas JS. The deleterious effects of methamphetamine use on initial presentation and clinical outcomes in aneurysmal subarachnoid hemorrhage. J Neurosurg 2012; 117:781.
- Chang TR, Kowalski RG, Caserta F, et al. Impact of acute cocaine use on aneurysmal subarachnoid hemorrhage. Stroke 2013; 44:1825.
- Longstreth WT, Nelson LM, Koepsell TD, van Belle G. Subarachnoid hemorrhage and hormonal factors in women. A population-based case-control study. Ann Intern Med 1994; 121:168.
- Mhurchu CN, Anderson C, Jamrozik K, et al. Hormonal factors and risk of aneurysmal subarachnoid hemorrhage: an international population-based, case-control study. Stroke 2001; 32:606.
- Algra AM, Klijn CJ, Helmerhorst FM, et al. Female risk factors for subarachnoid hemorrhage: a systematic review. Neurology 2012; 79:1230.
- Jung SY, Bae HJ, Park BJ, et al. Parity and risk of hemorrhagic strokes. Neurology 2010; 74:1424.
- Schmidt M, Johansen MB, Lash TL, et al. Antiplatelet drugs and risk of subarachnoid hemorrhage: a population-based case-control study. J Thromb Haemost 2010; 8:1468.
- Risselada R, Straatman H, van Kooten F, et al. Withdrawal of statins and risk of subarachnoid hemorrhage. Stroke 2009; 40:2887.
- STEHBENS WE. ANEURYSMS AND ANATOMICAL VARIATION OF CEREBRAL ARTERIES. Arch Pathol 1963; 75:45.
- Sandvei MS, Mathiesen EB, Vatten LJ, et al. Incidence and mortality of aneurysmal subarachnoid hemorrhage in two Norwegian cohorts, 1984-2007. Neurology 2011; 77:1833.
- Schievink WI, Karemaker JM, Hageman LM, van der Werf DJ. Circumstances surrounding aneurysmal subarachnoid hemorrhage. Surg Neurol 1989; 32:266.
- Anderson C, Ni Mhurchu C, Scott D, et al. Triggers of subarachnoid hemorrhage: role of physical exertion, smoking, and alcohol in the Australasian Cooperative Research on Subarachnoid Hemorrhage Study (ACROSS). Stroke 2003; 34:1771.
- Vlak MH, Rinkel GJ, Greebe P, et al. Trigger factors and their attributable risk for rupture of intracranial aneurysms: a case-crossover study. Stroke 2011; 42:1878.
- Shiue I, Arima H, Anderson CS, ACROSS Group. Life events and risk of subarachnoid hemorrhage: the australasian cooperative research on subarachnoid hemorrhage study (ACROSS). Stroke 2010; 41:1304.
- Penrose RJ. Life events before subarachnoid haemorrhage. J Psychosom Res 1972; 16:329.
- Biesbroek JM, van der Sprenkel JW, Algra A, Rinkel GJ. Prognosis of acute subdural haematoma from intracranial aneurysm rupture. J Neurol Neurosurg Psychiatry 2013; 84:254.
- Schuss P, Konczalla J, Platz J, et al. Aneurysm-related subarachnoid hemorrhage and acute subdural hematoma: single-center series and systematic review. J Neurosurg 2013; 118:984.
- Douglas MR, Daniel M, Lagord C, et al. High CSF transforming growth factor beta levels after subarachnoid haemorrhage: association with chronic communicating hydrocephalus. J Neurol Neurosurg Psychiatry 2009; 80:545.
- Zimmermann M, Seifert V. Endothelin and subarachnoid hemorrhage: an overview. Neurosurgery 1998; 43:863.
- Sobey CG, Faraci FM. Subarachnoid haemorrhage: what happens to the cerebral arteries? Clin Exp Pharmacol Physiol 1998; 25:867.
- Dhar R, Scalfani MT, Blackburn S, et al. Relationship between angiographic vasospasm and regional hypoperfusion in aneurysmal subarachnoid hemorrhage. Stroke 2012; 43:1788.
- Nornes H, Magnaes B. Intracranial pressure in patients with ruptured saccular aneurysm. J Neurosurg 1972; 36:537.
- Paré L, Delfino R, Leblanc R. The relationship of ventricular drainage to aneurysmal rebleeding. J Neurosurg 1992; 76:422.
- Brinker T, Seifert V, Stolke D. Acute changes in the dynamics of the cerebrospinal fluid system during experimental subarachnoid hemorrhage. Neurosurgery 1990; 27:369.
- Heinsoo M, Eelmäe J, Kuklane M, et al. The possible role of CSF hydrodynamic parameters following in management of SAH patients. Acta Neurochir Suppl 1998; 71:13.
- Sakowitz OW, Santos E, Nagel A, et al. Clusters of spreading depolarizations are associated with disturbed cerebral metabolism in patients with aneurysmal subarachnoid hemorrhage. Stroke 2013; 44:220.