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Comparative Study
. 2021 Aug 2;4(8):e2121921.
doi: 10.1001/jamanetworkopen.2021.21921.

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

Steven J Kittner  1 , Padmini Sekar  2 , Mary E Comeau  3 , Christopher D Anderson  4 , Gunjan Y Parikh  5 , Tachira Tavarez  6 , Matthew L Flaherty  2 , Fernando D Testai  7 , Michael R Frankel  8 , Michael L James  9 , Gene Sung  10 , Mitchell S V Elkind  11   12 , Bradford B Worrall  13 , Chelsea S Kidwell  14 , Nicole R Gonzales  15 , Sebastian Koch  16 , Christiana E Hall  17 , Lee Birnbaum  18 , Douglas Mayson  19 , Bruce Coull  14 , Marc D Malkoff  20 , Kevin N Sheth  21 , Jacob L McCauley  22 , Jennifer Osborne  2 , Misty Morgan  2 , Lee A Gilkerson  2 , Tyler P Behymer  2 , Stacie L Demel  2 , Charles J Moomaw  2 , Jonathan Rosand  4 , Carl D Langefeld  3 , Daniel Woo  2
Affiliations
Comparative Study

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

Steven J Kittner et al. JAMA Netw Open. .

Abstract

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 ɛ2 and ɛ4 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 ɛ2 and ɛ4 alleles of APOE and ICH in White individuals (eg, presence of APOE ɛ2 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Anderson reported receiving grants from the National Institutes of Health, the American Heart Association, Massachusetts General Hospital, and Bayer AG; personal fees from ApoPharma; and nonfinancial support from Invitae outside the submitted work. Dr Flaherty reported receiving grants from the CSL Behrnig speakers’ bureau and Portola/Alexion Pharmaceuticals speakers’ bureau outside the submitted work and holding a patent for a noninvasive central nervous system monitor intended for use after intracerebral hemorrhage. Dr Testai reported receiving research support from Lou and Chris Friedrich Philanthropic. Dr Frankel reported receiving grants from the Nico Corporation outside the submitted work. Dr Worrall reported serving as deputy editor for Neurology. Dr Koch reported having a patent for a medical device for treatment of intracerebral hemorrhage issued. Dr Hall reporting receiving support from the National Institute of Neurological Disease and Stroke from the University of Cincinnati and Johns Hopkins University during the conduct of the study. Dr Sheth reported receiving grants from the National Institutes of Health, the American Heart Association, Hyperfine, and Biogen; serving as chair of the data safety monitoring board for Zoll; owning equity in Alva; and receiving personal fees from NControl outside the submitted work. Dr Rosand reported receiving grants from National Institutes of Health and grants from American Heart Association during the conduct of the study and receiving personal fees from Boehringer Ingelheim outside the submitted work. No other disclosures were reported.

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