Marini S, et al. - In this case-control study of 13,124 adults, researchers assessed the links between established differences in intracerebral hemorrhage (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. Findings revealed an increased risk for lobar intracerebral hemorrhage in relation to having a copy of APOE ε4 alleles only in white individuals, but the same risk of APOE ε4 was seen among Hispanic individuals only when the excess burden of hypertension was propensity score–matched.

Methods

• This was a case-control study of primary ICH.
• Researchers applied a 2-stage clustering approach based on race/ethnicity and used stratification by a contributing study, to meta-analyze the association of APOE allele status on ICH risk.
• They modeled the association of APOE with the burden of hypertension across race/ethnic groups by using a propensity score analysis.
• They recruited primary ICH cases and controls from 3 hospital- and population-based studies in the United States and 8 in European sites in the International Stroke Genetic Consortium.
• From January 1, 1999, to December 31, 2017, they enrolled participants, excluding those with secondary causes of ICH.
• Within each participating study, regional matching of controls was implemented.
• Within each site, they performed structured interviews to systematically obtain clinical variables. 
• For all studies, APOE genotype was centrally determined.

Results

• This study included 13,124 participants (7,153 [54.5%] male with a median [interquartile range] age of 66 [56-76] years).
• Lobar ICH risk in white participants was observed in relation to 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); however, they did not find these links within self-identified Hispanic and black participants.
• After propensity score matching for hypertension burden,  Hispanic (OR, 1.14; 95% CI, 1.03-1.28; P = .01) but not black (OR, 1.02; 95% CI, 0.98-1.07; P = .25) participants showed a link between APOE ε4 and lobar ICH risk.
• Findings revealed no association of APOE ε2 and ε4 with nonlobar ICH risk in any race/ethnicity.