Supplementary Material for: Efficacy and Safety of Mechanical Thrombectomy in Elderly and Non-Elderly Patients with Large Vessel Occlusion Stroke A Systematic Review and Meta-Analysis

INTRODUCTION Mechanical thrombectomy (MT) is recommended for large vessel occlusion (LVO) stroke. However, most of the studies that investigated the superiority of MT over best medical management (BMM) alone included preponderantly non-elderly patients. Thus, there is uncertainty in relation to the efficacy of MT in the elderly. We aim to compare the effect of BMM to BMM plus (MT) among elderly and non-elderly patients with (LVO). METHODS We performed a systematic search of medical databases from inception to April 2023 to identify randomized studies that reported the functional outcome at 90 days by age for patients with LVO treated with MT vs. BMM. Patients were divided into elderly (>70 or >80 years, depending on the cut-off used in each study) and non-elderly. Outcomes were defined as excellent (modified Rankin Scale [mRS]≤1), good (mRS≤3), poor (mRS≥5), or death. Effect sizes were calculated by using random effects meta-analyses. Results were represented by odds ratio (OR) and their 95% confidence intervals (95% CI). RESULTS A total of 2,195 patients were included in the analysis (≥70 years, 7 trials, n= 696; ≥80 years, 2 trials, n=139). Non-elderly patients treated with MT had higher odds of excellent outcome (OR 3.05; 95% CI 2.23-4.18) and good outcome (OR 2.70; 95% CI 1.94-3.74), and lower odds of poor outcome (OR 0.54; 95% CI 0.40-0.72) and death (OR 0.63; 95% CI 0.41-0.96). Similarly, elderly patients treated with MT had higher odds of excellent (OR 2.39; 95% CI 1.05-5.45) and good outcomes (OR 2.18; 95% CI 1.43-3.33) and lower odds of poor outcome (OR 0.48; 95% CI 0.33-0.70) and mortality (OR 0.50; 0.26-0.95). When outcomes were analyzed by age subgroups, MT was associated with higher odds of good outcome in patients ≥70 years (OR 1.95, 95% CI 1.26-3.03) and ≥80 years (OR 4.43, 95% CI 1.02-19.23). DISCUSSION/CONCLUSION MT increases the likelihood of achieving a good outcome in elderly and non-elderly patients without increasing the risk of severe disability or death. MT, when otherwise clinically indicated, should be considered over BMM alone in both age groups

Ethnic and Racial Variation in Intracerebral Hemorrhage Risk Factors and Risk Factor Burden

Importance: Black and Hispanic individuals have an increased risk of intracerebral hemorrhage (ICH) compared with their White counterparts, but no large studies of ICH have been conducted in these disproportionately affected populations. Objective: To examine the prevalence, odds, and population attributable risk (PAR) percentage for established and novel risk factors for ICH, stratified by ICH location and racial/ethnic group. Design, Setting, and Participants: The Ethnic/Racial Variations of Intracerebral Hemorrhage Study was a case-control study of ICH among 3000 Black, Hispanic, and White individuals who experienced spontaneous ICH (1000 cases in each group). Recruitment was conducted between September 2009 and July 2016 at 19 US sites comprising 42 hospitals. Control participants were identified through random digit dialing and were matched to case participants by age (±5 years), sex, race/ethnicity, and geographic area. Data analyses were conducted from January 2019 to May 2020. Main Outcomes and Measures: Case and control participants underwent a standardized interview, physical measurement for body mass index, and genotyping for the ϵ2 and ϵ4 alleles of APOE, the gene encoding apolipoprotein E. Prevalence, multivariable adjusted odds ratio (OR), and PAR percentage were calculated for each risk factor in the entire ICH population and stratified by racial/ethnic group and by lobar or nonlobar location. Results: There were 1000 Black patients (median [interquartile range (IQR)] age, 57 [50-65] years, 425 [42.5%] women), 1000 Hispanic patients (median [IQR] age, 58 [49-69] years; 373 [37.3%] women), and 1000 White patients (median [IQR] age, 71 [59-80] years; 437 [43.7%] women). The mean (SD) age of patients with ICH was significantly lower among Black and Hispanic patients compared with White patients (eg, lobar ICH: Black, 62.2 [15.2] years; Hispanic, 62.5 [15.7] years; White, 71.0 [13.3] years). More than half of all ICH in Black and Hispanic patients was associated with treated or untreated hypertension (PAR for treated hypertension, Black patients: 53.6%; 95% CI, 46.4%-59.8%; Hispanic patients: 46.5%; 95% CI, 40.6%-51.8%; untreated hypertension, Black patients: 45.5%; 95% CI, 39.%-51.1%; Hispanic patients: 42.7%; 95% CI, 37.6%-47.3%). Lack of health insurance also had a disproportionate association with the PAR percentage for ICH in Black and Hispanic patients (Black patients: 21.7%; 95% CI, 17.5%-25.7%; Hispanic patients: 30.2%; 95% CI, 26.1%-34.1%; White patients: 5.8%; 95% CI, 3.3%-8.2%). A high sleep apnea risk score was associated with both lobar (OR, 1.68; 95% CI, 1.36-2.06) and nonlobar (OR, 1.62; 95% CI, 1.37-1.91) ICH, and high cholesterol was inversely associated only with nonlobar ICH (OR, 0.60; 95% CI, 0.52-0.70); both had no interactions with race and ethnicity. In contrast to the association between the ϵ2 and ϵ4 alleles of APOE and ICH in White individuals (eg, presence of APOE ϵ2 allele: OR, 1.84; 95% CI, 1.34-2.52), APOE alleles were not associated with lobar ICH among Black or Hispanic individuals. Conclusions and Relevance: This study found sleep apnea as a novel risk factor for ICH. The results suggest a strong contribution from inadequately treated hypertension and lack of health insurance to the disproportionate burden and earlier onset of ICH in Black and Hispanic populations. These findings emphasize the importance of addressing modifiable risk factors and the social determinants of health to reduce health disparities.. © 2021 American Medical Association. All rights reserved.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Association of Apolipoprotein e with Intracerebral Hemorrhage Risk by Race/Ethnicity : A Meta-analysis

Importance: Genetic studies of intracerebral hemorrhage (ICH) have focused mainly on white participants, but genetic risk may vary or could be concealed by differing nongenetic coexposures in nonwhite populations. Transethnic analysis of risk may clarify the role of genetics in ICH risk across populations. Objective: To evaluate associations between established differences in ICH risk by race/ethnicity and the variability in the risks of apolipoprotein E (APOE) ϵ4 alleles, the most potent genetic risk factor for ICH. Design, Setting, and Participants: This case-control study of primary ICH meta-analyzed the association of APOE allele status on ICH risk, applying a 2-stage clustering approach based on race/ethnicity and stratified by a contributing study. A propensity score analysis was used to model the association of APOE with the burden of hypertension across race/ethnic groups. Primary ICH cases and controls were collected from 3 hospital- and population-based studies in the United States and 8 in European sites in the International Stroke Genetic Consortium. Participants were enrolled from January 1, 1999, to December 31, 2017. Participants with secondary causes of ICH were excluded from enrollment. Controls were regionally matched within each participating study. Main Outcomes and Measures: Clinical variables were systematically obtained from structured interviews within each site. APOE genotype was centrally determined for all studies. Results: In total, 13124 participants (7153 [54.5%] male with a median [interquartile range] age of 66 [56-76] years) were included. In white participants, APOE ϵ2 (odds ratio [OR], 1.49; 95% CI, 1.24-1.80; P <.001) and APOE ϵ4 (OR, 1.51; 95% CI, 1.23-1.85; P <.001) were associated with lobar ICH risk; however, within self-identified Hispanic and black participants, no associations were found. After propensity score matching for hypertension burden, APOE ϵ4 was associated with lobar ICH risk among Hispanic (OR, 1.14; 95% CI, 1.03-1.28; P =.01) but not in black (OR, 1.02; 95% CI, 0.98-1.07; P =.25) participants. APOE ϵ2 and ϵ4 did not show an association with nonlobar ICH risk in any race/ethnicity. Conclusions and Relevance: APOE ϵ4 and ϵ2 alleles appear to affect lobar ICH risk variably by race/ethnicity, associations that are confirmed in white individuals but can be shown in Hispanic individuals only when the excess burden of hypertension is propensity score-matched; further studies are needed to explore the interactions between APOE alleles and environmental exposures that vary by race/ethnicity in representative populations at risk for ICH