Dataset Information

Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity: A Meta-analysis.

ABSTRACT: 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) ?4 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, 13?124 participants (7153 [54.5%] male with a median [interquartile range] age of 66 [56-76] years) were included. In white participants, APOE ?2 (odds ratio [OR],?1.49; 95% CI,?1.24-1.80; P?

SUBMITTER: Marini S

PROVIDER: S-EPMC6459133 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity: A Meta-analysis.

Marini Sandro S Crawford Katherine K Morotti Andrea A Lee Myung J MJ Pezzini Alessandro A Moomaw Charles J CJ Flaherty Matthew L ML Montaner Joan J Roquer Jaume J Jimenez-Conde Jordi J Giralt-Steinhauer Eva E Elosua Roberto R Cuadrado-Godia Elisa E Soriano-Tarraga Carolina C Slowik Agnieszka A Jagiella Jeremiasz M JM Pera Joanna J Urbanik Andrzej A Pichler Alexander A Hansen Björn M BM McCauley Jacob L JL Tirschwell David L DL Selim Magdy M Brown Devin L DL Silliman Scott L SL Worrall Bradford B BB Meschia James F JF Kidwell Chelsea S CS Testai Fernando D FD Kittner Steven J SJ Schmidt Helena H Enzinger Christian C Deary Ian J IJ Rannikmae Kristiina K Samarasekera Neshika N Al-Shahi Salman Rustam R Sudlow Catherine L CL Klijn Catharina J M CJM van Nieuwenhuizen Koen M KM Fernandez-Cadenas Israel I Delgado Pilar P Norrving Bo B Lindgren Arne A Goldstein Joshua N JN Viswanathan Anand A Greenberg Steven M SM Falcone Guido J GJ Biffi Alessandro A Langefeld Carl D CD Woo Daniel D Rosand Jonathan J Anderson Christopher D CD

JAMA neurology 20190401 4

<h4>Importance</h4>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.<h4>Objective</h4>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 ...[more]

PMID: 30726504

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Project description:ImportanceThe evidence linking chronic kidney disease (CKD) to spontaneous intracerebral hemorrhage (ICH) is inconclusive owing to possible confounding by comorbidities that frequently coexist in patients with these 2 diseases.ObjectiveTo determine whether there is an association between CKD and ICH risk.Design, setting, and participantsA 3-stage study that combined observational and genetic analyses was conducted. First, the association between CKD and ICH risk was tested in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, a multicenter case-control study in the US. All participants with available data on CKD from ERICH were included. Second, this analysis was replicated in the UK Biobank (UKB), an ongoing population study in the UK. All participants in the UKB were included in this study. Third, mendelian randomization analyses were implemented in the UKB using 27 CKD-related genetic variants to test for genetic associations. ERICH was conducted from August 1, 2010, to August 1, 2017, and observed participants for 1 year. The UKB enrolled participants between 2006 and 2010 and will continue to observe them for 30 years. Data analysis was performed from November 11, 2019, to May 10, 2022.ExposuresCKD stages 1 to 5.Main outcomes and measuresThe outcome of interest was ICH, ascertained in ERICH via expert review of neuroimages and in the UKB via a combination of self-reported data and International Statistical Classification of Diseases, Tenth Revision, codes.ResultsIn the ERICH study, a total of 2914 participants with ICH and 2954 controls who had available data on CKD were evaluated (mean [SD] age, 61.6 [14.0] years; 2433 female participants [41.5%]; 3435 male participants [58.5%]); CKD was found to be independently associated with higher risk of ICH (odds ratio [OR], 1.95; 95% CI, 1.35-2.89; P < .001). This association was not modified by race and ethnicity. Replication in the UKB with 1341 participants with ICH and 501 195 controls (mean [SD] age, 56.5 [8.1] years; 273 402 female participants [54.4%]; 229 134 male participants [45.6%]) confirmed this association (OR, 1.28; 95% CI, 1.01-1.62; P = .04). Mendelian randomization analyses indicated that genetically determined CKD was associated with ICH risk (OR, 1.56; 95% CI, 1.13-2.16; P = .007).Conclusions and relevanceIn this 3-stage study that combined observational and genetic analyses among study participants enrolled in 2 large observational studies with different characteristics and study designs, CKD was consistently associated with higher risk of ICH. Mendelian randomization analyses suggest that this association was causal. Further studies are needed to identify the specific biological pathways that mediate this association.

Project description:IMPORTANCE:Intracerebral hemorrhage (ICH) is the most severe form of stroke. Survivors are at high risk of recurrence, death, and worsening functional disability. OBJECTIVE:To investigate the association between blood pressure (BP) after index ICH and risk of recurrent ICH. DESIGN, SETTING, AND PARTICIPANTS:Single-site, tertiary care referral center observational study of 1145 of 2197 consecutive patients with ICH presenting from July 1994 to December 2013. A total of 1145 patients with ICH survived at least 90 days and were followed up through December 2013 (median follow-up of 36.8 months [minimum, 9.8 months]). EXPOSURES:Blood pressure measurements at 3, 6, 9, and 12 months, and every 6 months thereafter, obtained from medical personnel (inpatient hospital or outpatient clinic medical or nursing staff) or via patient self-report. Exposure was characterized in 3 ways: (1) recorded systolic and diastolic measurements; (2) classification as adequate or inadequate BP control based on American Heart Association/American Stroke Association recommendations; and (3) stage of hypertension based on Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 7 criteria. MAIN OUTCOMES AND MEASURES:Recurrent ICH and its location within the brain (lobar vs nonlobar). RESULTS:There were 102 recurrent ICH events among 505 survivors of lobar ICH and 44 recurrent ICH events among 640 survivors of nonlobar ICH. During follow-up adequate BP control was achieved on at least 1 measurement by 625 patients (54.6% of total [range, 49.2%-58.7%]) and consistently (ie, at all available time points) by 495 patients (43.2% of total [range, 34.5%-51.0%]). The event rate for lobar ICH was 84 per 1000 person-years among patients with inadequate BP control compared with 49 per 1000 person-years among patients with adequate BP control. For nonlobar ICH the event rate was 52 per 1000 person-years with inadequate BP control compared with 27 per 1000 person-years for patients with adequate BP control. In analyses modeling BP control as a time-varying variable, inadequate BP control was associated with higher risk of recurrence of both lobar ICH (hazard ratio [HR], 3.53 [95% CI, 1.65-7.54]) and nonlobar ICH (HR, 4.23 [95% CI, 1.02-17.52]). Systolic BP during follow-up was associated with increased risk of both lobar ICH recurrence (HR, 1.33 per 10-mm Hg increase [95% CI, 1.02-1.76]) and nonlobar ICH recurrence (HR, 1.54 [95% CI, 1.03-2.30]). Diastolic BP was associated with increased risk of nonlobar ICH recurrence (HR, 1.21 per 10-mm Hg increase [95% CI, 1.01-1.47]) but not with lobar ICH recurrence (HR, 1.36 [95% CI, 0.90-2.10]). CONCLUSIONS AND RELEVANCE:In this observational single-center cohort study of ICH survivors, reported BP measurements suggesting inadequate BP control during follow-up were associated with higher risk of both lobar and nonlobar ICH recurrence. These data suggest that randomized clinical trials are needed to address the benefits and risks of stricter BP control in ICH survivors.

Dataset Information

Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity: A Meta-analysis.

Publications

Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity: A Meta-analysis.

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