Risk Factors for Lobar and Non-Lobar Intracerebral Hemorrhage in Patients with Vascular Disease

Introduction Lobar and non-lobar non-traumatic intracerebral hemorrhage (ICH) are presumably caused by different types of small vessel diseases. The aim of this study was to assess risk factors for ICH according to location. Methods In two large prospective studies, SMART (n = 9088) and ESPRIT (n = 2625), including patients with manifest cardiovascular, cerebrovascular or peripheral artery disease or with vascular risk factors, we investigated potential risk factors for ICH during follow-up according to lobar or non-lobar location by Cox proportional hazards analyses. Results During 65,156 patient years of follow up 19 patients had lobar ICH (incidence rate 29, 95% CI 19–42 per 100,000 person-years) and 24 non-lobar ICH (incidence rate 37, 95% CI 26–51 per 100,000 person-years). Age significantly increased the risk of lobar ICH (HR per 10 years increase 1.90; 95% CI 1.17–3.10) in the multivariable analysis, but not of non-lobar hemorrhage. Anticoagulant medication (HR 3.49; 95% CI 1.20–10.2) and male sex (HR 3.79; 95% CI 1.13–12.8) increased the risk of non-lobar but not lobar ICH. Conclusion This study shows an elevated risk of future ICH in patients with manifestations of, or risk factors for, cardiovascular, cerebrovascular or peripheral artery disease. Our data suggest that risk factors for ICH vary according to location, supporting the hypothesis of a differential pathophysiology of lobar and non-lobar ICH.

[1]  Yibo Wang,et al.  Elevated plasma homocysteine was associated with hemorrhagic and ischemic stroke, but methylenetetrahydrofolate reductase gene C677T polymorphism was a risk factor for thrombotic stroke: a Multicenter Case-Control Study in China. , 2003, Stroke.

[2]  P. D. Bakker,et al.  LDL‐c‐linked SNPs are associated with LDL‐c and myocardial infarction despite lipid‐lowering therapy in patients with established vascular disease , 2014, European journal of clinical investigation.

[3]  A. Folsom,et al.  Risk Factors for Intracerebral Hemorrhage in a Pooled Prospective Study , 2007, Stroke.

[4]  K. Nakashima,et al.  [The Rotterdam study]. , 2011, Nihon rinsho. Japanese journal of clinical medicine.

[5]  Ale Algra,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 , 2010, The Lancet Neurology.

[6]  A. Algra,et al.  Second Manifestations of ARTerial disease (SMART) study: Rationale and design , 1999, European Journal of Epidemiology.

[7]  C. Sudlow,et al.  Is hypertension a more frequent risk factor for deep than for lobar supratentorial intracerebral haemorrhage? , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[8]  A. Hofman,et al.  Separate prediction of intracerebral hemorrhage and ischemic stroke , 2014, Neurology.

[9]  M. Maas,et al.  Coagulopathy Disproportionately Predisposes to Lobar Intracerebral Hemorrhage , 2013, Neurocritical Care.

[10]  S. Greenberg,et al.  Body Mass Index and Etiology of Intracerebral Hemorrhage , 2011, Stroke.

[11]  Michael Tin Chung Poon,et al.  Long-term prognosis after intracerebral haemorrhage: systematic review and meta-analysis , 2013, Journal of Neurology, Neurosurgery & Psychiatry.

[12]  W. Hauser,et al.  Depression is associated with impairment of ADL, not motor function in Parkinson disease. Authors' reply , 2006 .

[13]  S. Vidale.  Antithrombotic drugs and risk of hemorrhagic stroke in the general population , 2014, Neurology.

[14]  A. Algra,et al.  Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial , 2006, The Lancet.

[15]  S. Yusuf,et al.  Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study , 2010, The Lancet.

[16]  E. Schryver.  Design of ESPRIT: An International Randomized Trial for Secondary Prevention after Non-Disabling Cerebral Ischaemia of Arterial Origin , 2000 .

[17]  C. Moy,et al.  Risk Factors for Intracerebral Hemorrhage: The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study , 2013, Stroke.

[18]  D. Leys,et al.  Vitamin K Antagonists–Associated Cerebral Hemorrhages: What Are Their Characteristics? , 2013, Stroke.

[19]  Issa J Dahabreh,et al.  Index event bias as an explanation for the paradoxes of recurrence risk research. , 2011, JAMA.

[20]  X. Estivill,et al.  Variants at APOE influence risk of deep and lobar intracerebral hemorrhage , 2010, Annals of neurology.

[21]  D. Singer,et al.  The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. , 2004, Archives of internal medicine.

[22]  Y. Béjot,et al.  Intracerebral haemorrhage profiles are changing: results from the Dijon population-based study. , 2013, Brain : a journal of neurology.

[23]  J. Szaflarski,et al.  Genetic and Environmental Risk Factors for Intracerebral Hemorrhage: Preliminary Results of a Population-Based Study , 2002, Stroke.

[24]  M. L. Dell'Acqua,et al.  Antithrombotic medications and the etiology of intracerebral hemorrhage , 2014, Neurology.

[25]  E. de Schryver.  Design of ESPRIT: An International Randomized Trial for Secondary Prevention after Non-Disabling Cerebral Ischaemia of Arterial Origin , 2000, Cerebrovascular Diseases.

[26]  V. Feigin,et al.  Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review , 2009, The Lancet Neurology.

[27]  A. Hofman,et al.  Decreased Glomerular Filtration Rate Is a Risk Factor for Hemorrhagic But Not for Ischemic Stroke: The Rotterdam Study , 2007, Stroke.

[28]  M. Shlipak,et al.  Albuminuria and the risk of incident stroke and stroke types in older adults , 2010, Neurology.

[29]  A. Algra,et al.  Risk Factors for Intracerebral Hemorrhage in the General Population: A Systematic Review , 2003, Stroke.

[30]  J. Broderick,et al.  Risk factors for intracerebral hemorrhage differ according to hemorrhage location , 2012, Neurology.

[31]  W. Hauser,et al.  The incidence of deep and lobar intracerebral hemorrhage in whites, blacks, and Hispanics , 2005, Neurology.