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Intracerebral hemorrhage (ICH) is the stroke subtype with the worst prognosis and has no established acute treatment. ICH is classified as lobar or nonlobar based on the location of ruptured blood vessels within the brain. These different locations also signal different underlying vascular pathologies. Heritability estimates indicate a substantial genetic contribution to risk of ICH in both locations. We report a genome-wide association study of this condition that meta-analyzed data from six studies that enrolled individuals of European ancestry. Case subjects were ascertained by neurologists blinded to genotype data and classified as lobar or nonlobar based on brain computed tomography. ICH-free control subjects were sampled from ambulatory clinics or random digit dialing. Replication of signals identified in the discovery cohort with p < 1 × 10(-6) was pursued in an independent multiethnic sample utilizing both direct and genome-wide genotyping. The discovery phase included a case cohort of 1,545 individuals (664 lobar and 881 nonlobar cases) and a control cohort of 1,481 individuals and identified two susceptibility loci: for lobar ICH, chromosomal region 12q21.1 (rs11179580, odds ratio [OR] = 1.56, p = 7.0 × 10(-8)); and for nonlobar ICH, chromosomal region 1q22 (rs2984613, OR = 1.44, p = 1.6 × 10(-8)). The replication included a case cohort of 1,681 individuals (484 lobar and 1,194 nonlobar cases) and a control cohort of 2,261 individuals and corroborated the association for 1q22 (p = 6.5 × 10(-4); meta-analysis p = 2.2 × 10(-10)) but not for 12q21.1 (p = 0.55; meta-analysis p = 2.6 × 10(-5)). These results demonstrate biological heterogeneity across ICH subtypes and highlight the importance of ascertaining ICH cases accordingly.

IMPORTANCE Cerebral amyloid angiopathy-related inflammation (CAA-ri) is an important diagnosis to reach in clinical practice because many patients with the disease respond to immunosuppressive therapy. Reliable noninvasive diagnostic criteria for CAA-ri would allow some patients to avoid the risk of brain biopsy. OBJECTIVE To test the sensitivity and specificity of clinical and neuroimaging-based criteria for CAA-ri. DESIGN, SETTING, AND PARTICIPANTS We modified the previously proposed clinicoradiological criteria and retrospectively analyzed clinical medical records and magnetic resonance imaging fluid-attenuated inversion recovery and gradient-echo scans obtained from individuals with CAA-ri and noninflammatory CAA.

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 ...