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Association of Serum Bilirubin with the Severity and Outcomes of Intracerebral Hemorrhages.

ABSTRACT: Intracerebral hemorrhage (ICH) is the second most common subtype of stroke, and it is often associated with a high mortality rate and significant morbidity among survivors. Recent studies have shown that bilirubin, a product of heme metabolism, can exhibit cytoprotective, antioxidant and, anti-inflammatory properties. However, little is known about the role of bilirubin in combating several pathophysiological pathways caused by intracerebral bleeding in patients with ICH. In this study, data were collected retrospectively on 276 patients with ICH who were admitted to a university hospital between 5 January 2014 and 31 December 2017. We assessed the relationship between levels of total, direct, and indirect serum bilirubin and assessments of initial stroke severity and clinical outcomes by using Spearman's rank correlation and Kruskal-Wallis H tests. A secondary examination of the carrier protein albumin was also undertaken. Our study found that higher levels of direct bilirubin were correlated with worse admission Glasgow Coma Scales (GCS) (r_s = -0.17, p = 0.011), worse admission ICH Scores (r_s = 0.19, p = 0.008), and worse discharge modified Rankin Scales (mRS) (r_s = 0.15, p = 0.045). Direct bilirubin was still significantly correlated with discharge mRS after adjusting for temperature at admission (r_s = 0.16, p = 0.047), oxygen saturation at admission (r_s = 0.15, p = 0.048), white blood cell count (r_s = 0.18, p = 0.023), or Troponin T (r_s = 0.25, p = 0.001) using partial Spearman's correlation. No statistical significance was found between levels of total or indirect bilirubin and assessments of stroke severity and outcomes. In contrast, higher levels of albumin were correlated with better admission GCS (r_s = 0.13, p = 0.027), discharge GCS (r_s = 0.15, p = 0.013), and discharge mRS (r_s = -0.16, p = 0.023). We found that levels of total bilirubin, direct bilirubin, and albumin were all significantly related to discharge outcomes classified by discharge destinations (p = 0.036, p = 0.014, p = 0.016, respectively; Kruskal-Wallis H tests). In conclusion, higher direct bilirubin levels were associated with greater stroke severity at presentation and worse outcomes at discharge among patients with ICH. Higher levels of albumin were associated with lower stroke severity and better clinical outcomes. Future prospective studies on the free bioactive bilirubin are needed to better understand the intricate relationships between bilirubin and ICH.

SUBMITTER: Fu K

PROVIDER: S-EPMC8465680 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Over the past decade, many studies have reported the association of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) with clinical outcome of intracerebral hemorrhage (ICH). However, a broad consensus has not been reached. Objective: To evaluate the role of BNP/NT-proBNP levels in prognosis and disease severity assessment in patients with ICH. Methods: A systematic literature search was conducted utilizing PubMed, Embase, Web of Science and the Cochrane Library databases up to July 23, 2021. Studies that explored the association between BNP/NT-proBNP level and clinical outcome or disease severity in ICH patients were eligible. Outcome measures were all-cause mortality, poor functional outcome, adverse cardiac events and markers of disease severity. Results: Ten studies, involving 1,373 patients with ICH, met the inclusion criteria. Nine studies focused on clinical outcomes (five all-cause mortality, five functional outcomes, and one adverse cardiac event) and seven on disease severity. In terms of prognosis, all five studies showed an association between elevated BNP/NT-proBNP level and increased risk of all-cause mortality in ICH patients. Four of the five studies reported poor functional outcomes in patients with higher BNP/NT-proBNP levels and one study associated higher BNP/NT-proBNP levels with increased risk of adverse cardiac events. Moreover, two studies identified an additional predictive ability of BNP/NT-proBNP level beyond that of pre-existing prognostic variables. In terms of disease severity, five studies (71%) reported that BNP/NT-proBNP level correlated positively with hematoma volume in addition to ICH and GCS scores. Conclusion: Elevated BNP/NT-proBNP level is associated with increased risk of all-cause mortality, poor functional outcome, adverse cardiac events and disease severity in patients with ICH. Thus, BNP/NT-proBNP level is a promising prognostic indicator for ICH and also an effective marker of disease severity. Current evidence remains limited by the small number and high heterogeneity of included studies. Further appropriately designed, large-scale studies are required to confirm the current findings.

Project description:Intracerebral haemorrhage in the elderly is a severe manifestation of common forms of cerebral small vessel disease. Nearly 60% of intracerebral haemorrhage survivors will develop clinical manifestations of small vessel disease progression including recurrent haemorrhage, ischaemic stroke, dementia, late-life depression and gait impairment within 5 years. Blood pressure measurements following intracerebral haemorrhage are strongly associated with this risk. However, aggressive blood pressure lowering in the elderly carries substantial risks. In order to determine whether there might be an opportunity to select individuals at the highest risk for small vessel disease progression for aggressive blood pressure reduction, we investigated whether APOE gene variants ɛ2/ɛ4 modify the association between blood pressure and small vessel disease clinical progression after intracerebral haemorrhage. We conducted a single-centre longitudinal study at a tertiary care referral centre (Massachusetts General Hospital in Boston, MA, USA), analysing 716 consecutive survivors of acute intracerebral haemorrhage, enrolled from January 2006 to December 2016. We conducted research interviews at the time of enrolment and obtained APOE genotypes from peripheral venous blood samples. We followed patients longitudinally by means of validated phone-based research encounters, aimed at gathering measurements of systolic and diastolic blood pressure, as well as information on small vessel disease clinical outcomes (including recurrent haemorrhage, incident ischaemic stroke, incident dementia, incident depression and incident gait impairment). APOE ε4 and systolic blood pressure were associated with the risk of recurrent haemorrhage, ischaemic stroke and post-haemorrhage dementia, depression and gait impairment (all P < 0.05). APOE ε4 and systolic blood pressure interacted to increase the risk of recurrent haemorrhage, ischaemic stroke, dementia and gait impairment (all interaction P < 0.05). Among patients with elevated blood pressure following intracerebral haemorrhage (average systolic blood pressure 120-129 mmHg and diastolic blood pressure <80 mmHg) only those with one or more APOE ε4 copies were at increased risk for one or more small vessel disease outcomes (hazard ratio = 1.97, 95% confidence interval 1.17-3.31). Among haemorrhage survivors with hypertension (stage 1 and beyond) APOE genotype also stratified risk for all small vessel disease outcomes. In conclusion, APOE genotype modifies the already strong association of hypertension with multiple small vessel disease clinical outcomes among intracerebral haemorrhage survivors. These data raise the possibility that genetic screening could inform blood pressure treatment goals in this patient population.

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Association of Serum Bilirubin with the Severity and Outcomes of Intracerebral Hemorrhages.

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