Abstract
Hemorrhagic stroke accounts for approximately 5–15% of all acute stroke events worldwide, with its two most common subtypes being intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). Each of these hemorrhagic stroke subtypes accounts for 5–10% of all strokes, with noticeable variations in incidence across geographic regions and racial/ethnic groups. Despite significant advancements in neurocritical care and preventative strategies, morbidity and mortality related to ICH and SAH continue to represent a substantial public health problem worldwide. Indeed, despite accounting for a minority of stroke cases, hemorrhagic stroke accounts for almost half of all stroke-related morbidity and mortality. An in-depth understanding of the genetic, personal, and environmental risk factors influencing hemorrhagic stroke risk will be crucial to implementing novel, effective primary and secondary prevention strategies aimed at preserving lives and preventing disability among at-risk individuals. This chapter will focus on presenting existing evidence on risk factors for ICH and SAH, aiming at providing a critical review of published studies and highlighting current unresolved epidemiological questions pertaining to hemorrhagic stroke.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Qureshi AI, Tuhrim S, Broderick JP, et al. Spontaneous intracerebral hemorrhage. N Engl J Med. 2001;344:1450–60.
Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010;9:689–701.
Biffi A, Greenberg SM. Cerebral amyloid angiopathy: a systematic review. J Clin Neurol. 2011;7:1–9.
Biffi A, Anderson C, Battey TW, et al. Association between blood pressure control and risk of recurrent intracerebral hemorrhage. JAMA. 2015;314(9):904–12.
Rost NS, Greenberg SM, Rosand J. The genetic architecture of intracerebral hemorrhage. Stroke. 2008;39:2166–73.
Woo D, Sekar P, Chakraborty R, et al. Genetic epidemiology of intracerebral hemorrhage. J Stroke Cerebrovasc. 2005;14:239–43.
Devan WJ, Falcone GJ, Anderson CD, et al. Heritability estimates identify a substantial genetic contribution to risk and outcome of intracerebral hemorrhage. Stroke. 2013;44:1578–83.
Biffi A, Sonni A, Anderson CD, et al. Variants at APOE influence risk of deep and lobar intracerebral hemorrhage. Ann Neurol. 2010;68:934–43.
Biffi A, Shulman JM, Jagiella JM, et al. Genetic variation at CR1 increases risk of cerebral amyloid angiopathy. Neurology. 2012;78:334–41.
Valant V, Keenan B, Anderson C, et al. TOMM40 in cerebral amyloid angiopathy related intracerebral hemorrhage: comparative genetic analysis with Alzheimer’s disease. Transl Stroke Res. 2012;3(Suppl 1):S102–12.
Hamaguchi T, Okino S, Sodeyama N, et al. Association of a polymorphism of the transforming growth factor-{beta}1 gene with cerebral amyloid angiopathy. J Neurol Neurosur Ps. 2005;76:696–9.
Peila R, Yucesoy B, White LR, et al. A TGF-beta1 polymorphism association with dementia and neuropathologies: the HAAS. Neurobiol Aging. 2007;28:1367–73.
Woo D, Broderick JP. Spontaneous intracerebral hemorrhage: epidemiology and clinical presentation. Neurosurg Clin N Am. 2002;13:265–79.
Woo D, Falcone GJ, Devan WJ, et al. Meta-analysis of genome-wide association studies identifies 1q22 as a susceptibility locus for intracerebral hemorrhage. Am J Hum Genet. 2014;94:511–21.
Fornage M, Debette S, Bis JC, et al. Genome-wide association studies of cerebral white matter lesion burden: the CHARGE consortium. Ann Neurol. 2011;69:928–39.
Verhaaren BF, Debette S, Bis JC, et al. Multiethnic genome-wide association study of cerebral white matter hyperintensities on MRI. Circ Cardiovasc Genet. 2015;8:398–409.
Raffeld MR, Biffi A, Battey TW, et al. APOE epsilon4 and lipid levels affect risk of recurrent nonlobar intracerebral hemorrhage. Neurology. 2015;85:349–56.
Volonghi I, Pezzini A, Del Zotto E, et al. Role of COL4A1 in basement-membrane integrity and cerebral small-vessel disease. The COL4A1 stroke syndrome. Curr Med Chem. 2010;17:1317–24.
Gould DB, Phalan FC, Van Mil SE, et al. Role of COL4A1 in small-vessel disease and hemorrhagic stroke. N Engl J Med. 2006;354:1489–96.
Weng YC, Sonni A, Labelle-Dumais C, et al. COL4A1 mutations in patients with sporadic late-onset intracerebral hemorrhage. Ann Neurol. 2012;71:470–7.
Jeanne M, Labelle-Dumais C, Jorgensen J, et al. COL4A2 mutations impair COL4A1 and COL4A2 secretion and cause hemorrhagic stroke. Am J Hum Genet. 2012;90:91–101.
Rannikmae K, Davies G, Thomson PA, et al. Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease. Neurology. 2015;84:918–26.
Poon MT, Bell SM, Al-Shahi Salman R. Epidemiology of intracerebral haemorrhage. Front Neurol Neurosci. 2015;37:1–12.
Flaherty ML, Woo D, Haverbusch M, et al. Racial variations in location and risk of intracerebral hemorrhage. Stroke. 2005;36:934–7.
Labovitz DL, Halim A, Boden-Albala B, et al. The incidence of deep and lobar intracerebral hemorrhage in whites, blacks, and Hispanics. Neurology. 2005;65:518–22.
Woo D, Rosand J, Kidwell C, et al. The ethnic/racial variations of intracerebral hemorrhage (ERICH) study protocol. Stroke. 2013;44:e120–5.
Walsh KB, Woo D, Sekar P, et al. Untreated hypertension: a powerful risk factor for lobar and nonlobar intracerebral hemorrhage in whites, blacks, and hispanics. Circulation. 2016;134:1444–52.
Hong KS, Bang OY, Kang DW, et al. Stroke statistics in Korea: part I. Epidemiology and risk factors: a report from the Korean stroke society and clinical research center for stroke. J Stroke. 2013;15:2–20.
Toyoda K. Epidemiology and registry studies of stroke in Japan. J Stroke. 2013;15:21–6.
Benjamin EJ, Blaha MJ, Chiuve SE et al. Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation. 2017; 135:00–00.
Ariesen MJ, Claus SP, Rinkel GJE, et al. Risk factors for intracerebral hemorrhage in the general population: a systematic review. Stroke. 2003;34:2060–5.
Van Asch CJ, Luitse MJ, Rinkel GJ, et al. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol. 2010;9:167–76.
Zia E, Pessah-Rasmussen H, Khan FA, et al. Risk factors for primary intracerebral hemorrhage: a population-based nested case-control study. Cerebrovasc Dis. 2006;21:18–25.
Martini SR, Flaherty ML, Brown WM, et al. Risk factors for intracerebral hemorrhage differ according to hemorrhage location. Neurology. 2012;79:2275–82.
Jackson CA, Sudlow CLM. Is hypertension a more frequent risk factor for deep than for lobar supratentorial intracerebral haemorrhage? J Neurol Neurosurg. 2006;77:1244–52.
Rothwell PM, Howard SC, Dolan E, et al. Effects of beta blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke. Lancet Neurol. 2010;9:469–80.
Jolink WM, Klijn CJ, Brouwers PJ, et al. Time trends in incidence, case fatality, and mortality of intracerebral hemorrhage. Neurology. 2015;85:1318–24.
Lionakis N, Mendrinos D, Sanidas E, et al. Hypertension in the elderly. World J Cardiol. 2012;4:135–47.
Larsson SC, Wallin A, Wolk A, et al. Differing association of alcohol consumption with different stroke types: a systematic review and meta-analysis. BMC Med. 2016;14:178.
Xin X, He J, Frontini MG, et al. Effects of alcohol reduction on blood pressure: a meta-analysis of randomized controlled trials. Hypertension. 2001;38:1112–7.
Gorelick PB, Kelly MA. Alcohol as a risk factor for stroke. Heart Dis Stroke. 1992;1:255–8.
Thrift AG, Mcneil JJ, Forbes A, et al. Risk factors for cerebral hemorrhage in the era of well-controlled hypertension. Melbourne risk factor study (MERFS) group. Stroke. 1996;27:2020–5.
Giroud M, Creisson E, Fayolle H, et al. Risk factors for primary cerebral hemorrhage: a population-based study—the stroke registry of Dijon. Neuroepidemiology. 1995;14:20–6.
Iribarren C, Jacobs DR, Sadler M, et al. Low total serum cholesterol and intracerebral hemorrhagic stroke: is the association confined to elderly men? Stroke. 1996;27:1993–8.
Segal AZ, Chiu RI, Eggleston-Sexton PM, et al. Low cholesterol as a risk factor for primary intracerebral hemorrhage: a case-control study. Neuroepidemiology. 1999;18:185–93.
Yano K, Reed DM, Maclean CJ. Serum cholesterol and hemorrhagic stroke in the Honolulu heart program. Stroke. 1989;20:1460–5.
Wang X, Dong Y, Qi X, et al. Cholesterol levels and risk of hemorrhagic stroke: a systematic review and meta-analysis. Stroke. 2013;44:1833–9.
Xie L, Wu W, Chen J, et al. Cholesterol levels and hemorrhagic stroke risk in east Asian versus non-east Asian populations: a systematic review and meta-analysis. Neurologist. 2017;22:107–15.
Mckinney JS, Kostis WJ. Statin therapy and the risk of intracerebral hemorrhage: a meta-analysis of 31 randomized controlled trials. Stroke. 2012;43:2149–56.
Pandit AK, Kumar P, Kumar A, et al. High-dose statin therapy and risk of intracerebral hemorrhage: a meta-analysis. Acta Neurol Scand. 2016;134:22–8.
Bos MJ, Koudstaal PJ, Hofman A, et al. Decreased glomerular filtration rate is a risk factor for hemorrhagic but not for ischemic stroke: the Rotterdam study. Stroke. 2007;38:3127–32.
Ovbiagele B, Wing JJ, Menon RS, et al. Association of chronic kidney disease with cerebral microbleeds in patients with primary intracerebral hemorrhage. Stroke. 2013;44:2409–13.
Kim SH, Shin DW, Yun JM, et al. Kidney dysfunction and cerebral microbleeds in neurologically healthy adults. PLoS One. 2017;12:e0172210.
Hoirisch-Clapauch S, Nardi AE, Gris JC, et al. Are the antiplatelet and profibrinolytic properties of selective serotonin-reuptake inhibitors relevant to their brain effects? Thromb Res. 2014;134:11–6.
Pozzi M, Roccatagliata D, Sterzi R. Drug abuse and intracranial hemorrhage. Neurol Sci. 2008;29(Suppl 2):S269–70.
Treadwell SD, Robinson TG. Cocaine use and stroke. Postgrad Med J. 2007;83:389–94.
Mcevoy AW, Kitchen ND, Thomas DG. Intracerebral haemorrhage and drug abuse in young adults. Brit J Neurosurg. 2000;14:449–54.
Rosand J, Eckman MH, Knudsen KA, et al. The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Arch Intern Med. 2004;164:880–4.
Flaherty ML, Haverbusch M, Sekar P, et al. The increasing burden of anticoagulant-associated intracerebral hemorrhage. Stroke. 2006;37:623.
Shireman TI, Howard PA, Kresowik TF, et al. Combined anticoagulant-antiplatelet use and major bleeding events in elderly atrial fibrillation patients. Stroke. 2004;35:2362–7.
An SJ, Kim TJ, Yoon BW. Epidemiology, risk factors, and clinical features of intracerebral hemorrhage: an update. J Stroke. 2017;19:3–10.
Charidimou A, Shoamanesh A, Al-Shahi Salman R, et al. Cerebral amyloid angiopathy, cerebral microbleeds and implications for anticoagulation decisions: the need for a balanced approach. Int J Stroke. 2018;13:117–20.
Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146:857–67.
Gorelick PB. Combining aspirin with oral anticoagulant therapy: is this a safe and effective practice in patients with atrial fibrillation? Stroke. 2007;38:1652–4.
Investigators A, Connolly SJ, Pogue J, et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med. 2009;360:2066–78.
Covassin N, Somers VK. Sleep apnea, hypertension, and hemorrhagic stroke-deja vu all over again. J Am Soc Hypertens. 2016;10:197–200.
Floras JS. Hypertension and sleep apnea. Can J Cardiol. 2015;31:889–97.
Koo DL, Kim JY, Lim JS, et al. Cerebral microbleeds on MRI in patients with obstructive sleep apnea. J Clin Sleep Med. 2017;13:65–72.
Sacco S, Ricci S, Carolei A. Migraine and vascular diseases: a review of the evidence and potential implications for management. Cephalalgia. 2012;32:785–95.
Sacco S, Ornello R, Ripa P, et al. Migraine and hemorrhagic stroke: a meta-analysis. Stroke. 2013;44:3032–8.
Gaist D, Gonzalez-Perez A, Ashina M, et al. Migraine and risk of hemorrhagic stroke: a study based on data from general practice. J Headache Pain. 2014;15:74.
Macdonald RL, Schweizer TA. Spontaneous subarachnoid haemorrhage. Lancet. 2017;389:655–66.
Broderick JP, Brown RD Jr, Sauerbeck L, et al. Greater rupture risk for familial as compared to sporadic unruptured intracranial aneurysms. Stroke. 2009;40:1952–7.
Broderick JP, Sauerbeck LR, Foroud T, et al. Familial intracranial aneurysm (FIA) study protocol. BMC Med Genet. 2005;6(17)
Ruigrok YM, Buskens E, Rinkel GJ. Attributable risk of common and rare determinants of subarachnoid hemorrhage. Stroke. 2001;32:1173–5.
Alg VS, Sofat R, Houlden H, et al. Genetic risk factors for intracranial aneurysms: a meta-analysis in more than 116,000 individuals. Neurology. 2013;80:2154–65.
Yasuno K, Bilguvar K, Bijlenga P, et al. Genome-wide association study of intracranial aneurysm identifies three new risk loci. Nat Genet. 2010;42:420–5.
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. 2007;78:1365–72.
Eden SV, Meurer WJ, Sanchez BN, et al. Gender and ethnic differences in subarachnoid hemorrhage. Neurology. 2008;71:731–5.
Algra AM, Klijn CJ, Helmerhorst FM, et al. Female risk factors for subarachnoid hemorrhage: a systematic review. Neurology. 2012;79:1230–6.
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. 2012;83:1100–3.
Lindekleiv H, Sandvei MS, Njolstad I, et al. Sex differences in risk factors for aneurysmal subarachnoid hemorrhage: a cohort study. Neurology. 2011;76:637–43.
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;43:1885–9.
Andreasen TH, Bartek J Jr, Andresen M, et al. Modifiable risk factors for aneurysmal subarachnoid hemorrhage. Stroke. 2013;44:3607–12.
Yoon BW, Bae HJ, Hong KS, et al. Phenylpropanolamine contained in cold remedies and risk of hemorrhagic stroke. Neurology. 2007;68:146–9.
Lee SM, Choi NK, Lee BC, et al. Caffeine-containing medicines increase the risk of hemorrhagic stroke. Stroke. 2013;44:2139–43.
Feigin VL, Rinkel GJ, Lawes CM, et al. Risk factors for subarachnoid hemorrhage: an updated systematic review of epidemiological studies. Stroke. 2005;36:2773–80.
Kawate N, Kayaba K, Hara M, et al. Body mass index and incidence of subarachnoid hemorrhage in Japanese community residents: the Jichi medical school cohort study. J Stroke Cerebrovasc. 2017;26:1683–8.
Phan K, Moore JM, Griessenauer CJ, et al. Aspirin and risk of subarachnoid hemorrhage: systematic review and meta-analysis. Stroke. 2017;48:1210–7.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer Science+Business Media Singapore
About this chapter
Cite this chapter
Biffi, A. (2018). Risk Factors for Hemorrhagic Stroke. In: Lee, SH. (eds) Stroke Revisited: Hemorrhagic Stroke. Stroke Revisited. Springer, Singapore. https://doi.org/10.1007/978-981-10-1427-7_2
Download citation
DOI: https://doi.org/10.1007/978-981-10-1427-7_2
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-10-1426-0
Online ISBN: 978-981-10-1427-7
eBook Packages: MedicineMedicine (R0)