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Burden of risk alleles for hypertension increases risk of intracerebral hemorrhage.

ABSTRACT: Genetic variation influences risk of intracerebral hemorrhage (ICH). Hypertension (HTN) is a potent risk factor for ICH and several common genetic variants (single nucleotide polymorphisms [SNPs]) associated with blood pressure levels have been identified. We sought to determine whether the cumulative burden of blood pressure-related SNPs is associated with risk of ICH and pre-ICH diagnosis of HTN.We conducted a prospective multicenter case-control study in 2272 subjects of European ancestry (1025 cases and 1247 control subjects). Thirty-nine SNPs reported to be associated with blood pressure levels were identified from the National Human Genome Research Institute genomewide association study catalog. Single-SNP association analyses were performed for the outcomes ICH and pre-ICH HTN. Subsequently, weighted and unweighted genetic risk scores were constructed using these SNPs and entered as the independent variable in logistic regression models with ICH and pre-ICH HTN as the dependent variables.No single SNP was associated with either ICH or pre-ICH HTN. The blood pressure-based unweighted genetic risk score was associated with risk of ICH (OR, 1.11; 95% CI, 1.02-1.21; P=0.01) and the subset of ICH in deep regions (OR, 1.18; 95% CI, 1.07-1.30; P=0.001), but not with the subset of lobar ICH. The score was associated with a history of HTN among control subjects (OR, 1.17; 95% CI, 1.04-1.31; P=0.009) and ICH cases (OR, 1.15; 95% CI, 1.01-1.31; P=0.04). Similar results were obtained when using a weighted score.Increasing numbers of high blood pressure-related alleles are associated with increased risk of deep ICH as well as with clinically identified HTN.

SUBMITTER: Falcone GJ

PROVIDER: S-EPMC3479325 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Burden of risk alleles for hypertension increases risk of intracerebral hemorrhage.

Falcone Guido J GJ Biffi Alessandro A Devan William J WJ Jagiella Jeremiasz M JM Schmidt Helena H Kissela Brett B Hansen Björn M BM Jimenez-Conde Jordi J Giralt-Steinhauer Eva E Elosua Roberto R Cuadrado-Godia Elisa E Soriano Carolina C Ayres Alison M AM Schwab Kristin K Pera Joanna J Urbanik Andrzej A Rost Natalia S NS Goldstein Joshua N JN Viswanathan Anand A Pichler Alexander A Enzinger Christian C Norrving Bo B 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 Montaner Joan J Fernandez-Cadenas Israel I Delgado Pilar P Broderick Joseph P JP Greenberg Steven M SM Roquer Jaume J Lindgren Arne A Slowik Agnieszka A Schmidt Reinhold R Flaherty Matthew L ML Kleindorfer Dawn O DO Langefeld Carl D CD Woo Daniel D Rosand Jonathan J

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<h4>Background and purpose</h4>Genetic variation influences risk of intracerebral hemorrhage (ICH). Hypertension (HTN) is a potent risk factor for ICH and several common genetic variants (single nucleotide polymorphisms [SNPs]) associated with blood pressure levels have been identified. We sought to determine whether the cumulative burden of blood pressure-related SNPs is associated with risk of ICH and pre-ICH diagnosis of HTN.<h4>Methods</h4>We conducted a prospective multicenter case-control ...[more]

PMID: 22933587

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Project description:ImportanceBlack 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.ObjectiveTo 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 participantsThe 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 measuresCase 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.ResultsThere 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 relevanceThis 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.

Project description:The authors sought to explore whether hypertension classification was risk factor for lobar and non-lobar hypertensive intracerebral hemorrhage (HICH) and the prognosis in patients with hematoma. This retrospective cohort study was conducted on HICH patients admitted at the First Affiliated Hospital of Soochow University. Observations with first-ever intracerebral hemorrhage (ICH) were recruited. The authors divided the brain image into three groups according to the location of ICH to predict whether there were significant differences between lobar and non-lobar ICH. A Mann-Whitney U test was used and this retrospective trial also compared the operation and mortality rates. Our cohort included 209 patients (73.7% male; median age:60.5±16.7). The overall incidence of lobar HICH was less than non-lobar HICH (24.4% vs. 68.4%), 7.2% cases of mixed HICH was included in this analysis. In a Mann-Whitney U test analyze, it indicated that there were significant differences in hypertension classification between lobar and non-lobar HICH (Z = -3.3, p<.05). And the percentage of hematoma in lobar areas with relatively slightly high blood pressure (BP) (high normal and grade 1 hypertension) accounts for 52.9% versus 30.1% in non-lobar areas. The increasing trends of the prevalent rate of lobar ICH with BP rising were not remarkable. The non-lobar HICH showed a sharper increase in the condition of grade 3 hypertension compared with lobar HICH. During the period of research, the fatality of lobar hemorrhage was 2.9% versus 7.7% (non-lobar). Besides, the fatality incidence of HICH with relatively slightly high BP (high normal and grade 1 hypertension) was lower than poorly controlled hypertensive patients (grade 2 and grade 3 hypertension). (8.0% vs. 15.7%). The increase of hypertension classification will aggravate the occurrence of non-lobar ICH and positively corrected with BP, but not in lobar areas. It is essential to understand the distinction influence of hypertension classification between lobar and non-lobar ICH.

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Burden of risk alleles for hypertension increases risk of intracerebral hemorrhage.

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Burden of risk alleles for hypertension increases risk of intracerebral hemorrhage.

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