It is not clear whether subsets of patients with intracerebral hemorrhage (ICH) benefit from intensive blood pressure (BP) lowering. We evaluated whether white matter hyperintensities (WMH) burden influences response to this therapy.
Retrospective secondary analysis of the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 trial. Patients were randomized to intensive (systolic BP target: 110–139 mmHg) versus standard (systolic BP target: 140–179 mmHg) BP treatment with intravenous nicardipine within 4.5 h from onset between May 2011 and September 2015. WMH were rated on magnetic resonance images (fluid-attenuated inversion recovery sequences), defining moderate–severe WMH as total Fazekas scale score ≥ 3 (range 0–6). The main outcome was death or major disability at 90 days (modified Rankin scale ≥ 3). The secondary outcome was ICH expansion, defined as hematoma growth > 33% from baseline to follow-up CT scan. Predictors of the outcomes of interest were explored with multivariable logistic regression.
A total of 195/1000 patients had MRI images available for analysis, of whom 161 (82.6%) had moderate–severe WMH. When compared to patients with none–mild WMH, those with moderate–severe WMH did not have an increased risk of death or major disability (adjusted relative risk: 1.83, 95% CI 0.71–4.69) or ICH expansion (adjusted relative risk: 1.14, 95% CI 0.38–3.37). WMH burden did not modify the effect of intensive BP treatment on outcome (all p for interaction ≥ 0.2).
The majority of acute ICH patients have moderate–severe WMH, but advanced small vessel disease burden marked by WMH does not influence ICH-related outcomes or response to intensive BP reduction.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010;9(7):689–701.
Bakker SL, de Leeuw FE, de Groot JC, Hofman A, Koudstaal PJ, Breteler MM. Cerebral vasomotor reactivity and cerebral white matter lesions in the elderly. Neurology. 1999;52(3):578–83.
Kozera GM, Dubaniewicz M, Zdrojewski T, et al. Cerebral vasomotor reactivity and extent of white matter lesions in middle-aged men with arterial hypertension: a pilot study. Am J Hypertens. 2010;23(11):1198–203.
Purkayastha S, Fadar O, Mehregan A, et al. Impaired cerebrovascular hemodynamics are associated with cerebral white matter damage. J Cereb Blood Flow Metab. 2014;34(2):228–34.
Sato S, Delcourt C, Heeley E, et al. Significance of cerebral small-vessel disease in acute intracerebral hemorrhage. Stroke. 2016;47(3):701–7.
Goldstein JN, Brouwers HB, Romero J, et al. SCORE-IT: the Spot Sign score in restricting ICH growth─an Atach-II ancillary study. J Vasc Interv Neurol. 2012;5(supp):20–5.
Qureshi AI, Palesch YY, Barsan WG, et al. Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. N Engl J Med. 2016;375(11):1033–43.
Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol. 1987;149(2):351–6.
Shoamanesh A, Catanese L, Sakai O, Pikula A, Kase CS. Diffusion-weighted imaging hyperintensities in intracerebral hemorrhage: microinfarcts or microbleeds? Ann Neurol. 2013;73(6):795–6.
Greenberg SM, Vernooij MW, Cordonnier C, et al. Cerebral microbleeds: a field guide to their detection and interpretation. Lancet Neurol. 2009;8(2):165–74.
Wardlaw JM, Smith EE, Biessels GJ, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013;12(8):822–38.
Shoamanesh A, Morotti A, Romero JM, et al. Cerebral microbleeds and the effect of intensive blood pressure reduction on hematoma expansion and functional outcomes a secondary analysis of the ATACH-2 randomized clinical trial. JAMA Neurol. 2018;75(7):850–9.
Shoamanesh A, Catanese L, Romero JR, et al. High prevalence of cerebral microbleeds in inner city young stroke patients. J Stroke Cerebrovasc Dis. 2016;25(4):733–8.
Hemphill JC, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke. 2001;32(4):891–7.
Bias Delgado-Rodriguez M. J Epidemiol Community Heal. 2004;58(8):635–41.
Scheltens P, Erkinjunti T, Leys D, et al. White matter changes on CT and MRI: an overview of visual rating scales. European Task Force on Age-Related White Matter Changes. Eur Neurol. 1998;39(2):80–9.
Fazekas F, Barkhof F, Wahlund LO, et al. CT and MRI rating of white matter lesions. Cerebrovasc Dis. 2002;13(Suppl. 2):31–6.
Boulouis G, Van Etten ES, Charidimou A, et al. Association of key magnetic resonance imaging markers of cerebral small vessel disease with hematoma volume and expansion in patients with lobar and deep intracerebral hemorrhage. JAMA Neurol. 2016;73(12):1440–7.
Sykora M, Herweh C, Steiner T. The association between leukoaraiosis and poor outcome in intracerebral hemorrhage is not mediated by hematoma growth. J Stroke Cerebrovasc Dis. 2017;26(6):1328–33.
Kang S-J, Park B-J, Shim J-Y, Lee H-R, Hong J-M, Lee Y-J. Mean platelet volume (MPV) is associated with leukoaraiosis in the apparently healthy elderly. Arch Gerontol Geriatr. 2012;54(2):e118–21.
Balduini CL, Noris P. Platelet count and aging. Haematologica. 2014;99(6):953–5.
Ge Y, Grossman RI, Babb JS, Rabin ML, Mannon LJ, Kolson DL. Age-related total gray matter and white matter changes in normal adult brain. Part I: volumetric MR imaging analysis. AJNR Am J Neuroradiol. 2002;23(8):1327–33.
Charidimou A, Gang Q, Werring DJ. Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry. 2012;83(2):124–37.
The present study was supported by the following awards from the National Institute of Neurological Disorders and Stroke: 5R01NS073344. The funding source did not have any involvement in study design; data collection, analysis and interpretation; writing of the manuscript; or decision to submit the study for publication.
Conflict of interest
Andrea Morotti reports no disclosures. Ashkan Shoamanesh reports research funding from Bristol-Myer Squibb, Bayer AG and Servier Canada Inc., and consulting from Apopharma Inc., Bayer AG, Daiichi Sankyo, Servier Canada Inc., Bristol-Myer Squibb and Boehringer Ingelheim. Jamary Oliveira-Filho reports no disclosures. Frieder Schlunk reports no disclosures. Javier M. Romero reports no disclosures. Michael Jessel reports no disclosures. Alison Ayres reports no disclosures. Anastasia Vashkevich reports no disclosures. Kristin Schwab reports no disclosures. Christy Cassarly reports no disclosures. Renee’ Hebert Martin reports no disclosures. Steven M. Greenberg reports no disclosures. Adnan I. Qureshi reports no disclosures. Jonathan Rosand reports consulting for Pfizer, Boehringer Ingelheim. Joshua Goldstein reports research funding from Pfizer, Portola, and consulting from CSL Behring, Octapharma, Phillips.
Ethical Approval/Informed Consent
Local Institutional Review Boards approval was obtained at all ATACH-2 enrolling sites, and informed consent was obtained from all participants.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
About this article
Cite this article
Morotti, A., Shoamanesh, A., Oliveira-Filho, J. et al. White Matter Hyperintensities and Blood Pressure Lowering in Acute Intracerebral Hemorrhage: A Secondary Analysis of the ATACH-2 Trial. Neurocrit Care 32, 180–186 (2020). https://doi.org/10.1007/s12028-019-00761-0
- Intracerebral hemorrhage
- Small vessel disease
- White matter hyperintensities
- Blood pressure