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ObjectiveTo clarify whether recurrence risk for intracerebral hemorrhage (ICH) is higher among black and Hispanic individuals and whether this disparity is attributable to differences in blood pressure (BP) measurements and their variability.MethodsWe analyzed data from survivors of primary ICH enrolled in 2 separate studies: (1) the longitudinal study conducted at Massachusetts General Hospital (n = 759), and (2) the ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage) study (n = 1,532). Participants underwent structured interview at enrollment (including self-report of race/ethnicity) and were followed longitudinally via phone calls and review of medical records. We captured systolic BP (SBP) and diastolic BP measurements, and quantified variability as SBP and diastolic BP variation coefficients. We used multivariable (Cox regression) survival analysis to identify risk factors for ICH recurrence.ResultsWe followed 2,291 ICH survivors (1,121 white, 529 black, 605 Hispanic, and 36 of other race/ethnicity). Both black and Hispanic patients displayed higher SBP during follow-up (p < 0.05). Black participants also displayed greater SBP variability during follow-up (p = 0.032). In univariable analyses, black and Hispanic patients were at higher ICH recurrence risk (p < 0.05). After adjusting for BP measurements and their variability, both Hispanic (hazard ratio = 1.51, 95% confidence interval 1.14–2.00, p = 0.004) and black (hazard ratio = 1.98, 95% confidence interval 1.36–2.86, p < 0.001) patients remained at higher risk of ICH recurrence.ConclusionBlack and Hispanic patients are at higher risk of ICH recurrence; hypertension severity (average BP and its variability) does not fully account for this finding. Additional studies will be required to further elucidate determinants for this health disparity.

Intracerebral haemorrhage in the elderly is a severe manifestation of common forms of cerebral small vessel disease. Nearly 60% of intracerebral haemorrhage survivors will develop clinical manifestations of small vessel disease progression including recurrent haemorrhage, ischaemic stroke, dementia, late-life depression and gait impairment within 5 years. Blood pressure measurements following intracerebral haemorrhage are strongly associated with this risk. However, aggressive blood pressure lowering in the elderly carries substantial risks. In order to determine whether there might be an opportunity to select individuals at the highest risk for small vessel disease progression for aggressive blood pressure reduction, we investigated whether APOE gene variants ɛ2/ɛ4 modify the association between blood pressure and small vessel disease clinical progression after intracerebral haemorrhage. We conducted a single-centre longitudinal study at a tertiary care referral centre (Massachusetts General Hospital in Boston, MA, USA), analysing 716 consecutive survivors of acute intracerebral haemorrhage, enrolled from January 2006 to December 2016. We conducted research interviews at the time of enrolment and obtained APOE genotypes from peripheral venous blood samples. We followed patients longitudinally by means of validated phone-based research encounters, aimed at gathering measurements of systolic and diastolic blood pressure, as well as information on small vessel disease clinical outcomes (including recurrent haemorrhage, incident ischaemic stroke, incident dementia, incident depression and incident gait impairment). APOE ε4 and systolic blood pressure were associated with the risk of recurrent haemorrhage, ischaemic stroke and post-haemorrhage dementia, depression and gait impairment (all P, Intracerebral haemorrhage is a severe manifestation of cerebral small vessel disease, alongside ischaemic stroke, dementia, depression and gait impairment. We found that systolic blood pressure and APOE ε4 interact to increase risk of small vessel disease disorders. Genetic screening may, therefore, inform hypertension treatment goals for intracerebral haemorrhage survivors., Graphical Abstract Graphical Abstract

Background and Purpose— Whether to resume oral anticoagulation treatment after intracerebral hemorrhage (ICH) remains an unresolved question. Previous studies focused primarily on recurrent stroke after ICH. We sought to investigate the association between cardioembolic stroke risk, oral anticoagulation therapy resumption, and functional recovery among ICH survivors in the absence of recurrent stroke. Methods— We conducted a joint analysis of 3 observational studies: (1) the multicenter RETRACE study (German-Wide Multicenter Analysis of Oral Anticoagulation Associated Intracerebral Hemorrhage); (2) the Massachusetts General Hospital ICH study (n=166); and (3) the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage; n=131). We included 941 survivors of ICH in the setting of active oral anticoagulation therapy for prevention of cardioembolic stroke because of nonvalvular atrial fibrillation and without evidence of ischemic stroke and recurrent ICH at 1 year from the index event. We created univariable and multivariable models to explore associations between cardioembolic stroke risk (based on CHA 2 DS 2 -VASc scores) and functional recovery after ICH, defined as achieving modified Rankin Scale score of ≤3 at 1 year for participants with modified Rankin Scale score of >3 at discharge. Results— In multivariable analyses, the CHA 2 DS 2 -VASc score was associated with a decreased likelihood of functional recovery (odds ratio, 0.83 per 1 point increase; 95% CI, 0.79–0.86) at 1 year. Anticoagulation resumption was independently associated with a higher likelihood of recovery, regardless of CHA 2 DS 2 -VASc score (odds ratio, 1.89; 95% CI, 1.32–2.70). We found an interaction between CHA 2 DS 2 -VASc score and anticoagulation resumption in terms of association with increased likelihood of functional recovery (interaction P =0.011). Conclusions— Increasing cardioembolic stroke risk is associated with a decreased likelihood of functional recovery at 1 year after ICH, but this association was weaker among participants resuming oral anticoagulation therapy. These findings support, including recovery metrics, in future studies of anticoagulation resumption after ICH.

Introduction: Oral Anticoagulation Treatment (OAT) resumption remains an unresolved question in Intracerebral Hemorrhage (ICH) care. Previous studies focused on the effects of OAT resumption on recurrent stroke. Hypothesis: OAT resumption is associated with increased likelihood of functional recovery after ICH, even in the absence of symptomatic stroke recurrence. Methods: We analyzed data for 614 ICH survivors on OAT at time of stroke, who did not experience mortality or recurrent stroke during follow-up, enrolled in three observational studies: 1) the RETRACE study (n=317); 2) a longitudinal ICH study conducted in Boston, USA (n=166); 3) the ERICH study (n=131). We conducted univariable and multivariable analyses of associations between cardioembolic risk (defined by CHA 2 DS 2 -VASc score), OAT resumption, and functional recovery after ICH, defined as ≥ 1 point decrease in modified Rankin Scale (mRS) score at one year post-ICH vs. at discharge. Results: Among 614 participants, 153 (25%) resumed OAT. Individuals resuming OAT differed from those who did not only by higher CHA 2 DS 2 -VASc score (p=0.011). CHA 2 DS 2 -VASc score was associated with decreased likelihood of functional recovery at 1 year after ICH (Odds Ratio [OR] = 0.73 per 1 point increase, 95% Confidence Interval [CI] = 0.62-0.88, p 2 DS 2 -VASc score (OR=2.93, 95% CI = 1.25-4.61, p=0.001). Interaction analyses (Figure) clarified that subjects with higher CHA 2 DS 2 -VASc score benefited more from OAT resumption in terms of functional recovery (OR = 1.69, 95% CI = 1.20-2.38, p=0.003). Conclusions: Increasing cardioembolic risk associated with decreased likelihood of functional recovery after ICH. This effect was mitigated by OAT resumption, with greater benefit seen for subjects at high cardioembolic risk. These findings strongly support exploring recovery outcomes in future studies of OAT-ICH.